Field of the Invention The present invention relates to a stable dispersible formulation of arterolane maleate and piperaquine, wherein the formulation exhibits enhanced structural integrity and is able to rapidly disintegrate in water within 3 minutes. The dispersible formulation presents acceptable taste and leaves minimal residue in the mouth. The present invention also relates to a process for the preparation of said dispersible formulation. Background of the Invention Malaria is caused by Plasmodium parasites. The parasites are spread to people through the bites of infected female Anopheles mosquitoes. There are 5 parasite species that cause malaria in humans, and 2 of these species -Plasmodium falciparum and Plasmodium vivax pose the greatest threat. According to the World Health Organization estimates in December 20I5, there were 2I4 million cases of malaria and 438000 deaths in 2015. In 2014, there were 2.14million confirmed P. vivax cases globally, I 8% of which occurred in India only. Around 30% of P. vivax cases in India occurred in children aged I- I 4 years. Low cost, commonly used therapies are becoming increasingly ineffective. In many Sub-Saharan countries, 70 percent of malaria cases are resistant to the low-cost existing anti-malarial drugs such as chloroquine and sulphadoxine-pyrimethamine. The discovery ofartemisinin (qinghaosu), a naturally occurring endoperoxide sesquiterpene lactone isolated from the plant Artemisia annua, was a major breakthrough in the treatment of malaria, and a number of its precursors, metabolites, and semi-synthetic derivatives have also been shown to possess promising antimalarial properties. In 2006, after artemisinin had become the treatment of choice for malaria, the WHO called for an immediate halt to single-drug artemisinin preparations in favor of combinations of artemisinin with another antimalarial drug, to reduce the risk of resistance development. Fixed dose artemisinin combination therapies which are currently recommended by WHO for the treatment of uncomplicated falciparum malaria include: artemether + lumefantrine; artesunate + amodiaquine; artesunate + mefloquine; artesunate + sulfadoxinepyrimethamine; dihydroartemisinin + piperaquine; and artesunate + pyronaridine tetraphosphate. Oral tablets have been the most preferred dosage form for the administration of a wide variety of drugs; however, certain groups of patients, like pediatrics and geriatrics, face difficulty in swallowing these tablets and consequently this leads to incomplete regimens. In the case of malaria, non-compliance may even lead to the development of resistance. For such patients, dispersible formulations are the most suitable dosage forms as these combine the advantages of both dry and liquid formulations, have an acceptable taste, of1er a pleasant mouth feel, and leave minimal residue 2 in the mouth afler administration. Thus, there is a constant need for the development of a dispersible formulation based on artemisinin combination therapy which rapidly disintegrates in water and helps the patients to conveniently ingest and achieve compliance. Dispersible tablets of artemcther and lumcfantrine marketed under the trade name of Coartem@ were the first artcmisinin-based combination therapy developed specifically for children suflering fi·mn malaria. However, the Coartem@ tablet has to be administered in a twice daily dosage regimen based on the body weight of the child being administered the tablet. For example, for children with body weight of 5 kg to less than 15 kg, the dosing regimen includes one tablet twice a day for three days, and for children with body weight of 15 kg to less than 25 kg, the dosing regimen includes two tablets twice a day for three days. Thus, for the pediatric population suffering from malaria, there remains a need for miemisinin-based combination therapy exhibiting a simplified once daily dosing regimen. The scientists of the present invention have now developed an orally administered dispersible formulation of a fully synthetic miemisinin-based derivative, arterolane maleate, in combination with piperaquine. This formulation is advantageous for special groups of patients who have difficulty in swallowing conventional dosage forms, particularly pediatric patients. For pediatric use, the dosing regimen of the present invention is as simple as once daily for three days. The dispersible formulation of the present invention has been developed using dry processes and exhibits acceptable stability. Further, it has been surprisingly found that the dispersible formulation prepared in accordance with the present invention not only achieves rapid disintegration, but also ensures dosage uniformity by forming a homogeneous dispersion. Summary of the Invention The present invention provides a stable dispersible formulation of arterolane maleate and piperaquine, wherein the formulation disintegrates in water within 3 minutes. The dispersible formulation has an acceptable taste, offers a pleasant mouth feel, and leaves minimal residue in the mouth after administration. Said stable dispersible formulation is specially designed for the pediatric group of patients with a simplified dosage regimen. The present invention further provides a process for the preparation of said stable dispersible formulation. Detailed Description of the Invention A first aspect of the present invention provides a dispersible formulation comprising: (a) arterolane maleate in an amount offi·om about 20 mg to about 60 mg; and (b) piperaquine in an amount of from about !50 mg to about 200 mg wherein the formulation exhibits a mean Cmax of arterolane ranging from about 30 ng/mL to about 80 ng/mL and a mean Cmax of piperaquine ranging from about 200 ng/mL to about 450 ng/mL. 3 A second aspect of the present invention provides a dispersible f~mnulation comprising: (a) arterolane maleate in an amount of fi·om about 20 mg to about 60 mg; and (b) piperaquine in an amount of fi·om about !50 mg to about 200 mg wherein the formulation exhibits a mean exposure (A UC last) of arterolanc ranging from about 800 h.ng/mL to about 1200 h.ng/mL and a mean exposure (AUC last) of piperaquine ranging from about 35000 h.ng/mL to about 45000 h.ng/mL. According to one embodiment of the above aspects, there is provided a dispersible formulation of arterolane maleate and piperaquine, wherein the formulation is administered to pediatric patients of age 6 months to less than 2 years. A third aspect of the present invention provides a dispersible formulation comprising: (a) arterolane maleate in an amount of from about 60 mg to about 120 mg; and (b) piperaquine in an amount of from about 200 mg to about 450 mg wherein the formulation exhibits a mean Cmax of arterolane ranging from about 50 ng/mL to about 150 ng/mL and a mean Cmax of piperaquine ranging from about 300 ng/mL to about 700 ng/mL. A fourth aspect of the present invention provides a dispersible formulation comprising: (a) arterolane maleate in an amount of from about 60 mg to about 120 mg; and (b) piperaquine in an amount of from about 200 mg to about 450 mg wherein the formulation exhibits a mean exposure (AUC last) of arterolane ranging from about 1500 h.ng/mL to about 2500 h.ng/mL and a mean exposure (AUC last) ofpiperaquine ranging from about 70000 h.ng/mL to about 80000 h.ng/mL. According to one embodiment of the above aspects, there is provided a dispersible formulation of arterolane maleate and piperaquine, wherein the formulation is administered to pediatric patients of age 2 years to less than 6 years. A fifth aspect of the present invention provides a dispersible formulation comprising: (a) arterolane maleate in an amount of from about 100 mg to about 250 mg; and (b) piperaquine in an amount of from about 400 mg to about 650 mg wherein the formulation exhibits a mean Cmax of arterolane ranging from about 60 ng/mL to about 150 ng/mL and a mean Cmax of piperaquine ranging from about 250 ng/mL to about 700 ng/mL. A sixth aspect of the present invention provides a dispersible formulation comprising: (a) arterolane maleate in an amount of from about 100 mg to about 250 mg; and (b) piperaquine in an amount of fi·om about 400 mg to about 650 mg wherein the formulation exhibits a mean exposure (AUC last) of arterolane ranging from about I 000 h.ng/mL to about 3000 h.ng/mL and a mean exposure (AUC last) of piperaquine ranging from about 70000 h.ng/mL to about 85000 h.ng/mL. 4 According to one embodiment of the above aspects, there is provided a dispersible f(mnulation of arterolane maleate and piperaquinc, wherein the fC1rmulation is administered to pediatric patients of age 6 years to less than 12 years. A seventh aspect of the present invention provides a dispersible formulation comprising: (a) artcrolane maleate; and (b) piperaquine wherein the formulation is used for the treatment of malaria caused by Plasmodium falciparum or Plasmodium vivax following once daily administration for 3 days. A eighth aspect of the present invention provides a stable dispersible formulation of arterolane maleate and piperaquine comprising: (a) arterolane maleate; and (b) piperaquine wherein the formulation disintegrates in water within 3 minutes. According to one embodiment of the above aspect, there is provided a stable dispersible formulation of arterolane maleate and piperaquine, wherein the arterolane maleate and piperaquine are present in a weight ratio of about I : 1 to about I : I 0. According to another embodiment ofthe above aspect, there is provided a stable dispersible formulation of arterolane maleate and piperaquine, wherein arterolane maleate is present in an amount of fi·om about 20 mg to about 80 mg and piperaquine phosphate is present in an amount of from about 150 mg to about 200 mg. According to another embodiment of the above aspect, there is provided a stable dispersible formulation of mterolane maleate and piperaquine, wherein the formulation is prepared by a dry process. According to another embodiment ofthe above aspect, there is provided a stable dispersible formulation of mterolane maleate and piperaquine, wherein the formulation is prepared by a dry process, and wherein the dry process comprises direct compression or dry granulation. A ninth aspect of the present invention provides a stable dispersible formulation of arterolane maleate and piperaquine comprising: (a) arterolane maleate; (b) piperaquine; (c) one or more fillers; (d) one or more superdisintegrants; and (e) one or more suspending agents wherein the formulation disintegrates in water within 3 minutes. According to one embodiment of the above aspect, there is provided a stable dispersible 5 formulation of arterolane maleate and piperaquine comprising: (a) about2% to about 15% by weight of arterolane maleate; (b) about 15% to about 40% by weight ofpiperaquine; (c) about 30% to about 70% by weight of a flller; (d) about 5% to about 15% by weight of a superdisintegrant; and (e) about 1% to about 10% by weight of a suspending agent. According to another embodiment of the above aspect, there is provided a stable dispersible formulation of arterolane maleate and piperaquine comprising: (a) arterolane maleate; (b) piperaquine; (c) microcrystalline cellulose as a flller; (d) croscarmellosc as a superdisintegrant; and (e) water-dispersible cellulose as a suspending agent. A tenth aspect of the present invention provides a stable dispersible formulation of arterolane maleate and piperaquine comprising: (a) arterolane maleate; and (b) piperaquine wherein the formulation disintegrates in water within 3 minutes, and wherein the formulation is administered once daily for three days. The term "dispersible", as used herein, means a formulation that disintegrates within 3 minutes to form a dispersion, solution, non-gritty suspension, or slurry when placed either in water or in the oral cavity. The term "homogeneous dispersion", as used herein, means that the dispersion produced upon contact with water or saliva ensures the uniformity of arterolane maleate and piperaquine content for a reasonable period of time. The term "stable", as used herein, means percentage degradation of both arterolane maleate and piperaquine is not more than 5% of the initial value, after storage at 30°C and 75% relative humidity for a period of three years. The term "about", as used herein, refers to any value which lies within the range defined by a variation of up to ±10% of the value. The term "Cmax" refers to the maximum concentration of drug in the blood following administration of the formulation. The term "AUC" refers to the area under the time-plasma concentration curve after administration of the formulation. AUOast denotes the area under the plasma concentration versus time curve from 0 hours to the time of the last measureable concentration. 6 The term "parasite clearance time (PCT)" refers to the time in hours fi·om the initiation of therapy until the first of two successive negative smears for parasite is obtained. The term "fever clearance time (FCT)" refer to the time in hours fi·om the initiation of therapy until disappearance of fever for at least 24 hours. The term "mierolane maleate", as used herein, means the maleate salt of cis- adamanlane-2- spiro-3 '-8 '-[[ [(2 '-amino-2' -methylpropyl)amino ]carbonyl] methyl] -I' , 2', 4'- trioxaspiro[ 4.5]decane. The term further includes its individual enantiomers, diastereomers, racemates, and other isomers. The present invention comprises arterolane maleate in an amount of from about 2% to about 15% w/w of the total formulation. The term "piperaquine", as used herein, includes piperaquine free base as well as its pharmaceutically acceptable salts. Suitable salts of piperaquine include, but are not limited to, acid addition salts such as those made with phosphoric, maleic, malonic, succinic, fumaric, malic, tartaric, citric, methylsulfonic, hydrochloric, hydrobromic, hydroiodic, perchloric, sulfuric, nitric, acetic, propionic, glycolic, lactic pyruvic, benzoic, carbonic, cinnamic, mandelic, methane sulfonic, ethanesultonic, hydroxy ethane sulfonic, benezenesulfonic, p-toluene sulfonic, cyclohexanesulfamic, salicyclic, p-aminosalicylic, 2- phenoxybenzoic, and 2-acetoxybenzoic acids; and salts made with saccharin. Preferably, the salt is phosphoric acid, forming piperaquine phosphate. It further includes all individual enantiomers, diastereomers, racemates, and other isomers. The present invention comprises piperaquine as piperaquine phosphate in an amount of from about 15% to about 40% w/w of the total formulation. The present invention comprises arterolane maleate and piperaquine in a weight ratio of about I : I to about I : 10. The present invention comprises arterolane maleate (equivalent to arterolane) in a unit dose of25 mg, 37.5 mg, and 50 mg and piperaquine phosphate in a unit dose of 187.5 mg. The present invention provides a fixed dose combination of 37.5 mg of arterolane maleate (equivalent to arterolane) and 187.5 mg of piperaquine phosphate for pediatrics with a simple dosing regimen of once daily for three days. For pediatric patients, the present invention is advantageous as it provides a simplified dosing regimen based on the age group of the patient. In the commercially available pediatric formulation, i.e., Coartem® tablets, the dosing regimen is based upon the body weight of patient for which there is a requirement of a weighing machine before dispensing/deciding the dosage regimen; however, the ability to weigh the patient may not be feasible every time. The present invention provides a simplified dosing regimen based on the age group of pediatrics such as for children of age: - 6 months to less than 2 years, the dosing regimen is one tablet once a day for three days; 7 - 2 years to less than 6 years, the dosing regimen is two tablets once a day h1r three days; and - 6 years to less than 12 years, the dosing regimen is three tablets once a day for three days. The dispersible formulation of the present invention comprises a filler, a superdisintegrant, and a suspending agent. The dispersible formulation of the present invention comprises a filler in order to give sufficient bulk to the formulation and therefore facilitates the processing of the formulation. "I"he filler is selected from the group comprising microcrystalline cellulose, calcium disulfate, calcium trisulfate, calcium carbonate, lactose monohydrate, lactose anhydrous, sucrose, mannitol, sorbitol, calcium phosphate dibasic, calcium phosphate tribasic, kaolin, calcium silicate, maltodextrin, xylitol, erythritol, sorbitol, mannitol, starch, or mixtures thereof. The dispersible formulation of the present invention comprises a filler in an amount of from about 30% to about 70% w/w of the total formulation. The superdisintegrant is selected from the group comprising croscarmellose sodium, lowsubstituted hydroxypropylcellulose (L-HPC), sodium starch glycollate, carboxymethyl cellulose, calcium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, pregelatinized starch, microcrystalline cellulose, gum, alginic acid, or mixtures thereof. The dispersible formulation of the present invention comprises a superdisintegrant in an amount of from about 5% to about 15% w/w of the total formulation. In the present invention, the filler and superdisintegrant are present in a weight ratio of from about l: l to about l 0. The dispersible formulation of the present invention comprises a suspending agent which helps arterolanc maleate and piperaquine to remain uniformly distributed in a suspension and thus maintain content uniformity in the suspension. The suspending agent reduces the sedimentation of arterolane maleate and piperaquine, thereby ensuring the uniformity of the dose. The suspending agent is selected from the group comprising water-dispersible cell uloses, propylene glycol, polyethylene glycol, glycerin, or mixtures thereof In particular, water-dispersible cell uloses are co-processed, spray dried forms of microcrystalline cellulose and carboxymethyl cellulose sodium. These have been marketed under the trade names A vice!® RC-50 l (containing 7 .I% to 11.9% of sodium carboxymethyl cellulose), Avice]® RC-581 (containing 8.3% to 13.8% of sodium carboxymethyl cellulose), Avice!® RC-591 (containing 8.3% to 13.8% of sodium carboxymethyl cellulose). Avice!® RC-581, and Avice]® RC-591 differ on the basis of viscosities. The dispersible formulation of the present invention comprises a suspending agent in an amount of from about 1% to about 10% w/w of the total formulation. The dispersible formulation of the present invention fu1ther comprises pharmaceutically acceptable excipients. The term "pharmaceutically acceptable excipients", as used herein, may include any 8 physiologically inert additive used in the pharmaceutical arl of dispensing. Pharmaceutically acceptable excipienls may include lubricants, binders, sweetening agents, flavoring agents, and coloring agents. The lubricant is selected from the group comprising magnesium stearate, colloidal silicon dioxide, stearic acid, calcium stearate, zinc stearate, sodium stearyl fumarate, laic, hydrogenated castor oil, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax, silica gel, or mixtures thereof The binder is selected from the group comprising methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, microcrystalline cellulose, pull ulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, carboxyvinyl polymers, or mixtures thereof. The sweetening agent is selected from the group comprising aspartame, maltodextrin, cyclamate, acesulfame-K and its sodium and calcium salts, saccharin and its various salts, sucrose, sucralose, sorbitol, mannitol, xylitol, glucose, dextrose, fructose, or mixtures thereof. The flavoring agent is selected from the group comprising any natural or synthetic flavoring liquids such as volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins and extracts derived from plants, leaves, flowers, fruits, stems, and combinations thereof, including, but not limited to, spearmint, peppermint, lemon, caramel, banana, vanilla, orange, grape, lime or grapefruit citric oils, apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot, or other mint or fruit flavor essences; an aldehyde or ester such as benzaldehyde (cherry, almond), citra!, a-citra! (lemon, lime), neral, beta-citra! (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6-dimethyloctanal (green fruit), 2-dodedenal (citrus, mandarin); or mixtures thereof. Examples of coloring agents include, but are not limited to, any pharmaceutically acceptable natural or synthetic dyes such as red ferric oxide, titanium dioxide, Lake of Tartrazine, Lake of Quinoline Yellow, Lake of Sunset Yellow, Lake ofErythrosine, Lake Ponceau, Lake Allura Red, or mixtures thereof. The formulation ofthe present invention may be selected fi·om the group consisting of tablets, pellets, pills, granules, and powder. The pellets, pills, granules, and powder can be filled into sachets, the contents of which can be dissolved/dispersed in water. The preferred formulation is a dispersible tablet. The dispersible tablet is intended to be dispersed in water, milk, or any other suitable 9 consumable liquid prior to the administration, resulting in a homogenous dispersion. Further, the dispersible tablet may also be kept in the mouth to form a dispersion with the help of saliva. The key feature of the dispersible tablet is fast absorption of water or complete wetting of the tablet and disintegration of the associated particles for fast dissolution. Improving the wettability is a critical step as complete wetting on contacting the aqueous medium ensures the formation of a smooth suspension quickly after dispersion of the tablet. In the present invention, dispersible tablets are prepared by a dry process. The dry process comprises direct compression or dry granulation. Dry granulation may be compaction such as roller compaction or slugging. In another embodiment, the dispersible tablet may be further coated with one or more nonfunctionallayers comprising film-forming polymers and other coating additives. Examples of film-forming polymers include, but are not limited to, cellulose derivatives such as hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose, or mixtures thereof. Alternatively, commercially available coating compositions comprising film-forming polymers marketed under various trade names, such as Opadry®, may also be used for coating. The coating additives comprise one or more of plasticizers, glidants, opacifiers, and lubricants. Examples of solvents used for preparing a solution/dispersion of the coating ingredients include methyl alcohol, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, acetone, acetonitrile, chloroform, methylene chloride, water, or mixtures thereof. The invention is further illustrated by the following examples, which are provided for illustrative purposes only and should not be construed as limiting the scope of the invention in any way. Examples ,.------ --·--·-·--- --~-- -- Quantity %w/w Ingredients Example 1 Example 2 Example 3 Arterolane maleate 4.32 6.08 7.62 (equivalent to arterolane) Piperaquine phosphate 25.00 23.44 22.06 Microcrystalline cellulose 51.08 51.38 51.66 (Avicel® J>l:!J. .0 2) ···- Microcrystalline cellulose 2.00 2.00 2.00 and sodium sodium ·-·· 10 carboxymethyl cellulose (Avice!"'' RC521) ___ --1!-------·--·-+--------+---·---:-~------ Croscarmellose sodium ____ ().50 6.50 __ ~--·---6.50 . _ ~arta_111_e 8. 00 7 50 7 06 Qrflll~ Captarome 1.00 . ___ :===~~oo--_~:==: --------{oo- __ · -- r' 2V-"an,.,i,..ll.".a~~-----l--- ·-·-··0·.·1·· O·~- ---+----"-0'-'.1-"0------1----"0'-'.I"'O----i Colloidal silicon dioxide 0.50 0.50 0.50 ~-----+---------1----c--cc--·····- ·- _Magnesium stearate 1.50 --·-·--·-·-1.~()_ ___ ~·----·---·)·50 __ _Iota! weight ___ __!_....;7eo:S:'c'Oo.".O:'c'O_.,r11g__ _ 800.00 mg 850.00 mg Procedm·e: I. Arterolane maleate, microcrystalline cellulose, microcrystalline cellulose and sodium carboxymethyl cellulose, croscannellose sodium and colloidal silicon dioxide were sifted through a sieve # 36 BSS and piperaquine phosphate was sifted through a sieve # 18 BSS. 2. Aspartame, orange captarome and vanilla flavor were sifted through a sieve# 60 BSS. 3. Materials from steps I and 2 were blended and mixed for 30 minutes. 4. The blend of step 3 was lubricated with magnesium stearate. 5. The lubricated blend from step 4 was compressed using suitable size punches to obtain compressed tablets. Disintegration data Three batches of six tablets each prepared according to Example 2 were tested for disintegration using BP Disintegration apparatus. The results of disintegration are presented in Table I. Table 1: Disintegr·ation Times (Example 2) Batch Tablet 1 Tablet 2 Tablet 3 Tablet 4 Tablet 5 Tablet 6 No. I I minute I minute I minute I minute I minute I minute 2 I minute I minute I minute I minute I minute I minute 3 Less than Less than Less than Less than Less than 30 Less than 30 30 seconds 30 seconds 30 seconds 30 seconds seconds seconds In-vitro Dissolution data In-vitro drug release from the tablets prepared according to Example 2, was determined by dissolution for arterolane maleate in USP type II apparatus at 75 rpm, in 900ml of pH 4.5 acetate buffer with 2% tween 80 for 45 minutes. Similarly in-vitro drug release from the tablets prepared according to Example 2, was determined by dissolution for piperaquine phosphate in USP type II apparatus at 75 rpm, in 900ml ofO.Ol N hydrochloride for 45 minutes. The results of the dissolution study are presented in Table 2. 11 Table 2: In-vitro drug release (%w/w) at 45 minutes Time-~ _ Artero.lane r~9t_ 9eas~C8 gm/dL, absence of severe malnutrition, acute symptomatic uncomplicated P. falciparum malaria (parasite density of I ,000 and 100,000 asexual parasites/}.tL) and fever (axillary temperature ?:_37.5 °C) or a history of fever in the past 24 hours were enrolled in the study. 13 Randomization and Blinding Eligible patients were randomly assigned in a 2: I ratio to either AM-PQP orA-L group, respectively. Treatment Each patient received AM-PQP (37.5+187.5 mg) dispersible tablets, as a single daily dose once daily for 3 days, orA-L dispersible tablets twice a day for 3 days. Each tablet was dissolved in I 0 mL of drinking water. In AM-PQP group, the number of tablets in a single dose was according to age of the patients: 6 months to <2 years- I tablet, 2 years to <6 years- 2 tablets, and 6 years to :S:I2 years - 3 tablets. The study medication was administered irrespective of meals. The number of A-L tablets administered was according to the bodyweight of the patients: 5 to <15 kg - I tablet, 15 to <25 kg- 2 tablets and 25 to <35 kg - 3 tablets. The administration of A-L was followed by food or drinks rich in fat such as milk. In the event of vomiting within 30 min. of administration of the study drug, a repeat dose of study drug was given. If a patient vomited again within 30 min. of receiving a repeat dose of study medication, the patient was withdrawn from the study. The patients were discharged after the completion of3 days of treatment and, thereafter, were followed-up until day 42. Assessments Physical examination, vital signs measurement and clinical assessments were performed during the study. Body temperature (0 C) was recorded at screening, pre-dose on day 0, and at 6-hour intervals after the first dose of study medication until temperature normalized and it remained normal for 24 hours and on all follow-up days. Asexual and sexual parasites were counted. Blood was also collected for polymerase chain reaction (PCR) analysis. Genotyping by PCR analysis was conducted for those patients whose parasitemia reappeared after initial clearance. Three polymorphic genetic markers, mspl, msp2 and glurp, were used to distinguish recrudescence from new infection. Laboratory evaluations for safety [hematology, biochemistry, and urinalysis (dipstick)] were performed during the study. A urine pregnancy test (UPT) was performed at screening and on days 28 and 42 on all female patients of8 to 12 years. A 12-lead electrocardiograph (ECG) was performed at screening and between 2 and 4 hours after the 3rd dose of AM-PQP and 51h dose of A-L. Blood samples were collected from each enrolled patient for pharmacokinetic analysis of arterolane and piperaquine or artemether, dihydroartemisinin and lumefantrine. The compounds were measured using liquid chromatography tandem mass spectrometry methods. Statistical analysis Primary efficacy analysis was based on Per protocol population (PP) - PCR corrected. Intentto treat (ITT) analysis was used as supportive evidence. In addition, life-table analysis using Kaplan-Meier graph was done. Unless otherwise specified, all statistical tests were performed using a 2-sided, 5% level of signiilcance. Comparison between the treatments was done using 14 Wilson and Wald 95'Yo confidence interval (CI) of difference in proportion of patients with PCR corrected adequate clinical and parasitological response (ACPR). Proportion of patients with PCR corrected ACPR was compared between regimen groups using a logistic regression model including treatment and site as factors and baseline parasite count as covariate. Odds ratio and its 95% CI was calculated for treatment comparison. Analysis of PCT was done on data for all patients in ITT population. Kaplan-Meier (KM) survival probabilities for parasite clearance at each visit was estimated along with 95% CI for both the treatments. KM graphs were plotted and survival probabilities between two regimens were assessed either by Log rank test or Wilcoxon Gehan's test. Log rank method was followed in case the two survival curves did not cross each other; otherwise Wilcoxon Gehan's test was applied. The effect of treatment on PCT was investigated using Cox proportional hazards regression analysis, including factors tor regimen and study centre, as applicable. Hazard ratio between two regimens was calculated along with their confidence intervals. Analysis of FCT was done in a similar manner to PCT. The safety analysis was performed on the safety population. All statistical tests were performed using Statistical Analytical System (SAS) version 9.1.3 and in-house SAS DEAR reporting tool (Data Extraction, Analysis and Reporting). Results A total of859 patients were enrolled from India (101) and countries in Africa (758). Out of the total859 enrolled patients, 571 patients received AM-PQP and 288 patients received A-Land all were included in the safety and ITT analysis. A total of548 patients in AM-PQP arm and 279 patients in A-L ann were included in PP analysis. The baseline characteristics of the patients are presented in Table 5. Table 5: Demographic and Baseline Characteristics of the Randomized Patients Variable Arterolane Maleate- Piperaquine Phosphate Artemether- - (N=571) Lumefantrine (N=28~L Gender IN (%)1 Male 286 (50.1 %) 161 (55.9%) Female 285 (49.9%) 127 (44.1%) Age (months) Mean± SD 70.49±39.24 86.53±39.92 Range 6.0- 144 7- 149 Age (6 Months to <2 Years) months ·- N 86 15 Mean± SD 16.93±4.73 16.73±5.08 ·---~--- Range 6-23 7-22 Age (2 Year to <6 Years months --- N 212 88 - Mean± SD 47.54±13.80 44.67±13.41 Range 24-71 24-70 Age {6 Year to <12 Years) months N 273 185 1----- Mean± SD --- ······--··-·· 105.17±23.38 112.1 0±22.50 ·-~---~"-'""'" ····-~·····----- ~---····--~-------·--- Range 72- 144 72- 149 15 Range 15 -- 24.9 Weight (25 kg to <35 ke N 120 Mean± SD 29.0±2.83 Range ~~~~~~~------------------------------~------- Weight (>-35 kg) 25-34.9 ~~--~N~~---4--------------~3~--------------r----------~--------4 Mean± SD 6.8±1.80 Range 35- 38.60 Height (em) Mean± SD 111.4±21.96 Range 60- 193 P.falciparum Asexual Parasites (/ftL) at Day 0 Screening Mean± SD 33973.0±30466.05 33927.4±30666.20 Median 24623.0 23920.0 Temperature °C at Day 0 Screening Mean± SD 38.4±1.07 38.3±1.03 Median 38.4 38.3 History of Fever at Day 0 Screening Yes 567 (99.3%) 286 (99.3%) No 4 (0.7%) 2 (0.7%) P.falciparum Gametocytes (ii!L) at Day 0 Screening Mean± SD 37.53±520.13 13.72±103.41 Zero Count of Gametocytes f------,:-:-=-:-:-------T-------ccc-~c-c-c·c-c--··------r-----:--::-:---c··::-::;:;:-;c----l N (%) 535 (93.7%) 278 (96.5%) h}ficacy The primary outcome was the polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) at day 28 (cure rate). The cure rates were 100.0% and 98.5% [95% CI: !.48 (0.04 to 2.91 ); Table 6] in AM-PQP and A-L groups, respectively, in Per Protocol (PP) population, and 96.0% and 95.8% [95% CI: 0.14 (- 2.68 to 2.95); Table 7] in Intent to Treat (ITT) population. Similar cure rates were observed at day 42 in both ITT and PP population. No 16 recrudescence was reported in AM-PQP group compared to 4 patients (1.5%) in A-L group who developed recrudescence at or before day 28. (Table 6). In the ITT population, PCR corrected ACPR on day 42 was 94.4% vs. 93.1% [95% Cl: 1.34 ( -2.15 to 4.83); Table 7] in AM-PQP and A-L groups, respectively. The PCR corrected ACPR survival probability at day 28 and day 42 was found to be higher in AM-PQP group as compared to A-L group in the ITT population (Log-rank p=0.0018, day 28; and Log-rank p=O.OOOl, day 42). The median parasite clearance time (PCT) was 24 hours in both the treatment groups. The median fever clearance time (FCT) was 6 hours in AM-PQP and 12 hours in A-L group. At the end of the study, gametocytes were cleared and comparable in both the treatment groups (Table 8). Table 6: Adequate Clinical and Parasitological Response (ACPR) By Time-Point (PerProtocol Population) .• ··--c Arterolane Artemether- Difference Wald maleate- PQI' lumefantrine 95% CI Day 28 (N=827) 548 279 PCR-uncorrected ACPR 546 (99.6%) 267 (95.7%) 3.94 (1.5, 6.37) Total failures 2 (0.4%) 12 (4.3%) • Late clinical failure I (0.2%) 5 (1.8%) • Late parasitological failure I (0.2%) 7 (2.5%) Day 28 (N-817) 546 271 PCR-corrected ACPR 546 (100.0%) 267 (98.5%) 1.48 (0.04, 2.91) Total failures 0 4 (1.5%) • Recrudescence 0 4 (1.5%) Day 42 (N=805) 538 267 PCR-uncorrected ACPR 531 (98.7%) 248 (92.9%) 5.81 (2.59, 9.04) Total failures 7 (1.3%) 19 (7.1%) • Late clinical failure 2 (0.4%) I 0 (3.7%) • Late parasitological failure 5 (0.9%) 8 (3.0%) -· ... • P. vivax and mixed infection or 0 I (0.4%) infection due to any Plasmodium species other than P. falciparum Day 42 (N=783) 532 251 1.01 (-0.39, 2.4) l'CR-corrected ACPR 531 (99.8%) 248 (98.8%) Total failures I (0.2%) 3 (1.2%) .. • Recrudescence I (0.2%) 3 (1.2%) Table 7: Adequate Clinical and Parasitological Response (ACPR) By Time-Point (IntentionTo- Treat Population) Arterolane Artemether- Difference Wald maleate- l'Ql' lumefantrine 95% CI Day 28 (N=859) 571 288 PCR-uncorrected ACI'R 546 (95.6%) 269 (93.4%) 2.22 (-1.1, 5.54) Total failures 25 (4.4%) 19 (6.6%) --"·--- • Late Parasitological Failure (LPF) I (0.2%) 7 (2.4%) .. r----· --- • Late Clinical Failure (LCF) 1 (0.2%) 5 (1.7%) • Adverse event/severe malaria/SAE I I (1.9%) 2 (0.7%) ·- 17 ~------~~-~---··· ·--- ~-~~~ -- -~--~·-··- -.--·-··----· ····--·----- ------ ---- • Protocol violation including non- I (0.2%) I (0.3%) compliance -----~~---~~-------~- ------ --~- -------~--- • Patient's request or the request of 8 (1.4%) 2 (0.7%) - [laticnt's LAR for withdrawal . -----~ --···· ---~--- ---·-··· • Inform consent Withdrawal I (0.2%) 0 -- -- ---·· - ------ ·-· • Lost to F_oHow up 2 (0.4%) 2 _co. 2:/oL ___ _ --- -· - Day 28 (N=859) 571 288 I'CR-corrected ACI'R 548 (96.0%) 276 (95.8%) 0.14 (-2.68,29}L -- ----· --- Total failures 23 c 4.0'lioL 12 (4.2%) - - • Recrudescence 0 4 (1.4%) ~-- - - • Sample not am[llified 0 I (0.3%) 0 Adverse event/severe malaria/SA£ II (1.9%) 2 (0.7%) -- --~ • Protocol violation including non- I (0.2%) I (0.3%) compliance - -----·-·· • Patient's request or the request of 8 (1.4%) 2 (0.7%) LAR for withdrawal • Inform consent withdrawal I (0.2%) 0 ·-- • Lost to Follow up 2 (0.4%) 2 (0.7%) Dal' 42 (N-859} 571 288 I'CR-uncorrected ACI'R 531 (93.0%) 248 (86.1%) 6.88 (2.37,.39) Total failures 40 (7.0%) 40 (13.9%) • Late Clinical Failure (LCF) 3 (0.5%) 16 (5.6%) -· • Late Parasitological Failure (LPF) 6 (1.1 %) 14 (4.9%) • Adverse event/severe malaria/SA£ I I (1.9%) 2 (0.7%) -- • Protocol violation including non- 1 (0.2%) 1 (0.3%) compliance • P. vivax and mixed infection or 0 I (0.3%) infection due to any plasmodium species other than the P. falcioarum • Patient's request or the request of 9(1.6%) 2 (0.7%) patient's LAR for withdrawal • Lost to Follow up 9 (1.6%) 4 (1.4%) • Other 1 (0.2%) 0 Day 42 (N-859) 571 288 ~)l-corrected ACI'R 539 (94.4%) 268 (93.1%l 1.34(-2.15,4.83) Total failures 32 (5.6%) 20 (6.9%) • Sample not amplified 0 4 (1.4%) ·-- • Recrudescence 1 (0.2%~ 7 (2.4%) • Adverse event/severe malaria/SA£ I 1 (1.9%) 2 (0.7%) • Protocol violation including non- I (0.2%) I (0.3%) compliance 0 Patient's request or the request of 9 (1.6%) 2 (0.7%) patient's LAR • Lost to Follow up 9(1.6%) 4 (I .4%) • Other I (0.2%) 0 18 Table 8: Proportion of Patients having Zero Gametocyte Counts (ITT Population) ·:--;- --~~-- --------~ -----~---- --··-~-- Time Point Arterolanc Maleate- Pipcraquinc Artemcthcr- Lumcfantrin e ·- Pltosphate ··-···-····- ,- - N No. of Patients with Zero N No. of Patients with Zero ·-. <_;amcto_<:ytcs ('Y.,) --f----------- GametOC;)'tes (')/o Baseline 571 538 (94.2%) 288 274 (95.1 %) ·-·-·-~- - Day 7 539 512 (95.0%) 279 276 (98.9%) - ----- Day 14 540 527 (97.6%) 272 271 (99.6%) - -~··- Day 28 544 543 (99.8%) 269 267 (99.3%) Day 42 534 534 (100.0%) 255 255 ( 100.0%) Safety The overall incidence of treatment-emergent adverse events was comparable in the two treatment group (Table 9). Table 9: Incidence of Adverse Events in Safety Population [No.(%) of Patients] System Organ Class Arterolanc Maleate-Piperaquinc Prcfened Term Phosphate Artemcther-Lumefantrine (N=571) (N=288) -·- No. of patients with at least one 534 (93.5%) 267 (92.7%} adverse event Clinical Adverse Events Anaemia 279 (48.9%) 145 (50.3%) Ear pain 0 1 (0.3%) Blepharitis I (0.2%) 0 Conjunctival hyperaemia I (0.2%) 0 Abdominal distension 6 (1.1 %) I (0.3%) Abdominal pain 5 (0.9%) I (0.3%) Constipation 2 (0.4%) 0 Diarrhoea 12(2.1%) 4 (I .4%) Dyspepsia I (0.2%) I (0.3%) Flatulence I (0.2%) 0 -·- Mouth ulceration I (0.2%) 0 Nausea 9 (1.6%) 6(2.1%) Vomiting 96 (16.8%) 20 (6.9%) Chills 6 (!.!%) 6 (2.1%} Fatigue 6 (LI%) 9(3.1%) Malaise 5 (0.9%) 5 (1.7%) Pyrexia 27 (4.7%) 28 (9.7%) Abscess I (0.2%) I (0.3%) Body tinea I (0.2%) 0 --···· - - I (0:2%) ·--. Bronchitis 2 (0.7%) Bronchopneumonia 0 I (0.3%) Candida infection I (0.2%) 0 Ear infection I (0.2'Yo) I (0.3%) Gastroenteritis 2 (0.4%) 2 (0.7%) ·-- Lice infestation I (0.2%) I (0.3%) Mumps -- 0 I (0.3%) _Phar;)'ngitis ----·-· - 4 (0.7%) - I (0.3%) Rhinitis 1 (0.2%) 4(1.4%)_ __ ~ 19 Para meter N Mean SD CV'Yo ,-- ,, ____ ,,_ I ··-----·------'"""" ---~---··--·-·-·---- ·········-··--~ System Organ Class Art'erolanc Maleafe-Piperaquine Preferred Tenn Phosphate Artcmcthcr-Lumcfantrine !-:::-········-------·-----·-·· ---... , ... _,, ___ (N=571) -- (N:}lj8) ··- Sepsis I (0.2%) 0 r.r•·inca capitis - .. --~·-· - 0 -- ---·· ------· 2 (0.4%) ---- Tonsillitis 5 (0.9%) - 2 (0.7%) Upper resrirator~ tract infecti()."._. ..• 6(1.1%) ----~-·-· 2 (0.7%) ·--- Urinary tract infection I (0.2Y.,) 0 -· Limb injury ·-··· I (0.2%) 0 Decreased appetite II (1.9%) II (3.8%) ---· ·---·· ··-~--- ·- Headache 15 (2.6%) 18 (6_.3%) ·-~ ··---- Cough 63 (11.0%) 21 (7.3%) Nasal congestion I (0.2%) 0 ·- Pneumonitis I (0.2%) 0 -···· .. -- Rhinorrhoea 12 (2.1%) ·~ 7 (2.4%) Snoring 2 (0.4%) 0 Tachypnoea I (0.2%) 0 • Wheezing I (0.2%) 0 Dermatitis I (0.2%) 0 Hyperhidrosis 4 (0.7%) 6 (2.1%) ···--·- ·-- Rash I (0.2%) 0 Skin hypopigmentation I (0.2%) 0 Pallor 2 (0.4%) 0 - Pharmacokinetics The mean maximum plasma concentration (Cmax) for arterolane was 57.90, 87.52 and 93.08 ng/mL and mean exposure (AUCiast) ofarterolane was 985.19,2157.36 and 2158.47 h.ng/mL across age groups of 6 months to <2 years, 2 to <6 years and 6 to ::;12 years, respectively. Similarly, the mean Cmax ofpiperaquine was 315.08,550.27 and 523.75 ng/mL and mean exposure was 38018.82, 74148.42 and 77032.99 h.ng/mL across age groups of 6 months to <2 years, 2 to <6 years and 6 to ::;12 years, respectively. Mean pharmacokinetic parameters for arterolane, piperaquine, artemether, dihydroartemisinin (active metabolite of artemether) and lumefantrine are presented in Tables I Oa, lOb and JOe. Table lOa: Mean pharmacokinetic pam meters of arterolane, piperaquine, artemether, dihydroartemisinin, lumefantrine in pediatric patients with P. falciparum malaria across sites in Africa and India 6 MONTHS TO <2 YEARS (1 TABLET 5 KG TO <15 KG (1 TABLET TWICE DAILY) ONCE DAILY) Dihydroartemisi . Arterolane Piperaquine Artemether nin Lumefantrine Cmax AUC1ast Cm:u: AUC1ast Cm:u: AUC1ast Cma~ AUC1ast Cma~ AUC1,.st (ng/m (h.ng/m (f!g/m (h.f!g/ (ng/mL) (h.ng/mL) (ng/mL) (h.ng/ mL) (ng/mL) (h.ng/mL) Ll L) 1,) mL) ··--"---" . - 83 83 83 83 58 58 38 38 62 62 57.90 985.19 315.08 38018.82 76.24 1614.48 59.39 1336.20 4.365 417.91 112.15 1269.23 426.81 33873.31 72.13 1608.49 70.29 1788.10 3.903 1205.99 193.70 128.83 135.46 89.10 94.61 99.63 118.34 133.82 89.42 288.57 20 .--· Table I Ob: Mean pharmacokinetic parameters of arterolane, piperaquine, artemether, dihydroartemisinin, lumcfantrine in pediatric patients with P. j{dciparum malaria across sites in Africa and India -~-----~--------···-·---.. ·~----~-.. ·----~-----·-·· 2 YEARS TO <6 YEARS (2 15 KG TO <25 KG (2 TABLETS TWICE DAILY) TABLETS Ol"/CE DAILY) Arterolane Piperaquine Artemether Dihydroartemis Lumefantrine in in Para -····-· ------,- ·- meter Cmax AUC1ast Cmax AUOast Cnwx AUC1ast Cmax A lJCJasl Cmax AUC'"" (ng/mL) (h.ng/m (ng/ (h.ng/ (ng/m (h.ng/ (ng/m (h.ng/m (rtg/ (h.ftg/ r--- -- L) mL) mL}_ L) mL) L) L) mL) mL) ·- r--N- 192 192 192 192 98 98 80 80 98 98 -- 6.92 Mean 550.2 122.5 87.52 2157.36 7 74148.42 I 2815.68 75.63 4083.47 0 647.71 SD 417.0 10381.9 5.01 85.50 2272.55 0 51013.81 92.63 4404.91 72.28 7 3 727.50 ..• CV% 72.4 97.70 I 05.34 75.78 68.80 75.61 156.44 95.57 254.24 3 112.32 Table lOc: Mean pharmacokinetic parameters of arterolanc, piperaquine, artemether, dihydroartemisinin, lumefantrinc in pediatric patients with P. falciparum malaria across sites in Africa and India 6 YEARS TO ::;12 YEARS (3 TABLETS 25 TO <35 KG (3 TABLETS TWICE DAILY) ONCE DAILY) Arterolane l'iperaquine Artemether Dihydroartemis Lumefantriue in in l'aram AUC,,, Cmnx AUC,.,, Cmax AUC,.,, Cmax AUC,.,, Cmax AUC,.,, eter Cmax (ng/mL) (h.ng/m (ng/ (h.ng/m (ng/ (h.ng/m (ng/ (h.ng/m (ftg/ (h.ftg/m L) mL) L) mL) L) mL) L) mL) L) N 257 257 257 257 94 94 84 84 96 96 Mean 77032.9 122.0 2815.47 94.83 4384.85 93.08 2158.47 523.75 9 2 7.317 682.19 SD 56648.5 97.20 4614.53 74.58 8207.18 73.44 1770.97 369.91 9 5.952 893.76 CV% 78.90 82.05 70.63 73.54 79.66 163.90 78.65 187.17 81.35 131.01 Conclusion The efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dosed once daily was found to be comparable to artemether-lumefantrine dosed twice daily in the treatment of uncomplicated P. falciparum malaria in pediatric patients. StudyB The primary aim of this study was to compare the safety and efficacy of once-daily dosed arterolane maleate-piperaquine phosphate (AM-PQP) dispersible tablets with that of chloroquine phosphate in pediatric patients with acute uncomplicated Plasmodium vivax malaria. Study design A phase III, open-labeled, comparative, active-controlled, parallel-group, multicenteric study of 42 days duration including 3 days of treatment period was undertaken. 21 Patients Inclusion and exclusion criteria Patients with P. vivax mono-infection, aged between 6 months to 12 years, weighing 2:5 kg were included into the study. Additional inclusion criteria were parasite density of>250/rll blood, presence of axillary temperature :C:37.5°C or oral temperature :C:38°C or fever in the previous 24 hours. Exclusion criteria included mixed Plasmodium infection; severe malaria; haemoglobin <8 gm/dl; history ofhaemolytic anaemia or methaemoglobinaemia; known allergy to arterolane maleate, artesunate, artemisinin-derived products, piperaquine, chloroquine, primaquine or any other related drugs; evidence of gastro-intestinal dysfunction that could alter absorption or motility (e.g., diarrhoea defined as >three episodes of watery stools in the previous 24 hours or patients who have had three episodes of vomiting within 24 hours prior to screening); use of concomitant medications that could induce haemolysis or haemolytic anaemia or depressants of myeloid element of the bone marrow; any anti-malarial treatment taken during one month prior to screening; ongoing prophylaxis with drugs having anti-malarial activity such as cotrimoxazole, doxycycline and malarone; concomitant drug metabolized by the cytochrome enzyme CYP2D6 (flecainide, metoprolol, imipramine, amitriptyline, clomipramine, etc.); participation in any other investigational drug study of at least three months prior to screening; any other significant disease, electrocardiogram (ECG) abnormalities (included QTc interval >450 msec at screening and cardiac conduction disorders, with the exception of right bundle branch block); evidence of significant renal or hepatic impairment (serum creatinine > 1.5 upper limit of normal, ULN, aspartate transaminase >2.5 x ULN, alanine transaminase >2.5 x ULN, serum bilirubin >3 mg/dL, serum potassium and serum sodium< lower limit of normal); splenectomy conducted earlier as confirmed by history or clinical examination; G6PD-deficient patients; retinal/ visual field defects or auditory defects and history of psoriasis and porphyria. Randomization and blinding Patients were randomized in a ratio of 2:1 to receive either AM-PQP dispersible tablets or chloroquine phosphate oral suspension/tablets according to the randomization schedule. Treatment In AM-PQP group, the number oftablets in a single dose was according to age of the patients: 6 months to <2 years - 1 tablet, 2 years to <6 years - 2 tablets, and 6 years to ::012 years - 3 tablets. The study medication was administered irrespective of meals. Each tablet was dissolved in I 0 mL of drinking water with continuous swirling. In chloroquine group, chloroquine oral suspension (50 mg/ 5ml) was administered in patients <9 years and chloroquine tablet (containing 250 mg of chloroquine phosphate) was administered in patients 2:9 years. A single daily dose for 3 days was provided 22 according to the age category of the patients. In the event of vomiting within 30 min. of administration of the study drug, a repeat dose of study drug was given. If a patient vomited again within 30 min. of receiving a repeat dose of study medication, the patient was withdrawn from the study. After completion of three days treatment, the dispersible tablets of primaquine phosphate 2.5 mg were provided to the study patients for 14 consecutive days i.e., starting on day 3 following the 3-day treatment period as an anti-relapse measure. The single dose was provided according to the age category of the patients. Clinical and laboratorv assessments Physical examination, vital signs measurement and clinical assessments were performed during the study. Body temperature (0 C) was recorded at screening, pre-dose on day 0, and at 6-hour intervals after the first dose of study medication until temperature normalized and it remained normal for 24 hours and on all follow-up days. Blood smears were prepared and parasite counts measured at screening, predose and at six hourly intervals following the first dose of study medication until two consecutive negative smears were obtained, thereafter at day 3 and all follow-up visits. Laboratory evaluations for safety [hematology, biochemistry, and urinalysis (dipstick)] were performed during the study. A 12-lead electrocardiograph (ECG) was performed at screening and between 2 and 4 hours after the 3rd dose of AM-PQP or chloroquine. Outcomes The primary efficacy outcome was proportion of aparasitaemic and afebrile patients at 72 hours. Secondary efficacy outcome included cure rate on day 28, parasite clearance time (PCT) and fever clearance time (FCT). Cure rate on day 42 was also reported. Cure rate is defined as the absence of parasitaemia irrespective of axillary/oral temperature without previously meeting any of the criteria of treatment failures. Safety endpoints included incidence of adverse events or clinically significant changes in clinical and laboratory parameters, ECG, vital signs, or physical examination findings. Statistical considerations Efficacy analyses (primary and secondary efficacy-variables) were based on Per Protocol (PP) population. Analysis of PCT and FCT was done on-all available subjects in ITT population. Lifetable analysis using Kaplan-Meier graph was done. Unless otherwise specified, all statistical tests were performed using a 2-sided, 5% level of significance. Descriptive statistics for continuous and ordinal variables included mean, standard deviation, 95% confidence interval of the mean, as well as median, minimum, maximum values and-quartiles. Time to event data-(PCT, FCT) was summarized by number of events, median time and quartiles. Proportion of~aparasitemic and afebrile patients at 72 hours, cure rate on day 28 and day 42 were estimated-along with their 95% contldence interval lor each treatment ann. Between treatment arm comparison was done using Fisher's exact test and 2- 23 sided 95% Wilson's contldence intervaL-Centre effect was assessed using Cochran-Mentei-J-Iaenzel (CMH) and logistic regression, if applicable. Wald test (without continuity corrected) 95% contldence interval (Cl) based on-normal approximation was also presented. Kaplan-Meier (KM) survival probabilities for parasite-clearance at each visit was estimated along with 95%CI for both the treatments. Median time to-failure along with 95%CI was determined. KM graphs were plotted and survival probabilities-between two regimens were assessed either by Log rank test or Wilcoxon Gehan' s test. Log rank-method was followed in case the two survival curves did not cross each other; otherwise Wilcoxon Gehan' s test was applied. The eflect of treatment on PCT was investigated using Cox-proportional hazards regression analysis, including factors for treatment and study centre. Hazard-ratio between two treatments was calculated along with their confidence intervals. Analysis of-FCT was done in a similar manner to PCT. The safety analysis was performed on the safety population. All statistical tests were performed using Statistical Analytical System (SAS) version 9.1.3 and in-house SAS DEAR reporting tool (Data Extraction, Analysis and Reporting). Results A total of 164 patients were randomized with Ill patients receiving AM-PQP and 53 patients receiving chloroquine. One-hundred and sixty (160) patients completed the entire duration of the study, i.e., day 42. Patient demography and baseline characteristics are summarized in Table 11. Table II: Demographic and Baseline Characteristics of the Randomized Patients FDC of Arterolane Maleate and PQP Chloroquine {N=lll) {N=53) Gender [N {%)] Male 75 (67.6%) 34 (64.2%) Female I 36 (32.4%) 19 (35.8%) Age {months) Mean± SO 72.98 ± 41.04 79.96 ± 38.44 Range 12.00- 144.00 _1 11.00-144.00 IA~e (6 Months to <2 Year) months IN 17 3 Mean± SO 18.18 "' 3.45 15.00± 3.61 Range 12.00-23.00 11.00- 18.00 IAge {2 Year to <6 Year) months N 42 22 Mean± SO 47.95 ± 13.05 50.59 ± 12.83 -· Range 24.00- 71.00 24.00- 71.00 ~e (6 Year to <12 \'ear months --- -----~-- N 52 28 Mean± SO 111.12 ± 22.21 II 0.00 ± 24.69 Range 72.00- 144.00 72.00- 144.00 Race Asian Ill (100.0%) 53(100.0%) Wei~ht (kg} Mean± SO I 19.Hc7.75 ___ ] 20.1 ± 7.23 Range 8.00-38.10 8.60- 38.00 -- 24 r:::;·~···-~~~-------~~------- -·--------··----·-·----·---------·······------ ~~~-l)~----l- - -~---:~~; -1 12fi::~7o ---_-_ ---r-· 710°~-J-~~~~~1~-~-= .P. vivax Asexual Parasites (/J!L) a--t- ·D""a-y- 0 Screen.i.n. g --~·-·---·-j··--·~----- ~-io$1) I 3474.lio2566.~?.... _ 3313.5±2883.15 __ Median 3121.0 2691.0 . ----· -----j !T_ernatraemia ________ _ _____ }{Q.9'X.:co)'---------i-------0 ___ _ H )Okalaemia _______________ ___ 6 (5.4'Yo) ___ __ 5 (9.4-'-'X'-'o) _ H onatraemia ----+ ____ lj_O.Jl')-(.::,o '-----!--------:-()_ __ Leuk()cyturia__ ___ I i.Q.9%)1___ I (1.9%) __ Proteinuria 2 0.::-Sc:.:'X..::o"-) __ ...J.... ______ _Q ____ .......J Conclusion The results of this trial demonstrated the comparable efficacy and safety of fixed dose combination dispersible tablets of arterolane maleate 37.5 mg and piperaquine phosphate 187.5 mg as compared to chloroquine for the treatment of uncomplicated P. vivax malaria in pediatric patients. WE CLAIM: 1. A dispersible formulation comprising: (a) arterolane maleate in an amount of from about 20 mg to about 60 mg; and (b) piperaquine in an amount of fi·om about 150 mg to about 200 mg wherein the formulation exhibits a mean Cmax of arterolane ranging from about 40 ng/mL to about 80 nglmL and a mean Cmax of piperaquinc ranging from about 200 nglmL to about450 ng/mL. 2. A dispersible formulation comprising: (a) arterolane maleate in an amount of from about 20 mg to about 60 mg; and (b) piperaquine in an amount of from about 150 mg to about 200 mg wherein the formulation exhibits a mean exposure (AUC last) of arterolane ranging from about 800 h.ng/mL to about 1200 h.ng/mL and a mean exposure (AUC last) ofpiperaquine ranging from about 35000 h.ng/mL to about 45000 h.ng/mL. 3. The dispersible formulation according to claim 1 or 2, wherein the formulation IS administered to pediatric patients of age 6 months to less than 2 years. 4. A dispersible formulation comprising: (a) arterolane maleate in an amount of from about 60 mg to about 120 mg; and (b) piperaquine in an amount of from about 200 mg to about 450 mg wherein the formulation exhibits a mean Cmax of arterolane ranging from about 50 ng/mL to about 150 ng/mL and a mean Cmax of piperaquine ranging from about 300 ng/mL to about 700 ng/mL. 5. A dispersible formulation comprising: (a) arterolane maleate in an amount of from about 60 mg to about 120 mg; and (b) piperaquine in an amount of from about 200 mg to about 450 mg wherein the formulation exhibits a mean exposure (AUC last) of arterolane ranging from about 1500 h.ng/mL to about 2500 h.ng/mL and a mean exposure (AUC last) ofpiperaquine ranging from about 70000 h.ng/mL to about 80000 h.ng/mL. 6. The dispersible formulation according to claim 4 or 5, wherein the formulation is administered to pediatric patients of age 2 years to less than 6 years. 29 7. A dispersible formulation comprising: (a) artcrolane maleate in an amount of f!·om about 100 mg to about 250 mg; and (b) piperaquine in an amount of fl·om about 400 mg to about 650 mg wherein the formulation exhibits a mean Cnnx of arterolane ranging from about 60 ng/mL to about 150 ng/mL and a mean Cmnx of piperaquine ranging ti·om about 250 ng/mL to about 700 ng/mL. 8. A dispersible formulation comprising: (a) arterolane maleate in an amount of from about 100 mg to about 250 mg; and (b) piperaquine in an amount of ti·om about 400 mg to about 650 mg wherein the formulation exhibits a mean exposure (AUC Inst) of arterolane ranging from about 1000 h.ng/mL to about 3000 h.ng/mL and a mean exposure (AUC last) ofpiperaquine ranging from about 70000 h.ng/mL to about 85000 h.ng/mL. 9. The dispersible formulation according to claim 7 or 8, wherein the formulation IS administered to pediatric patients of age 6 years to less than 12 years. 10. A dispersible formulation comprising: (a) arterolane maleate; and (b) piperaquine wherein the formulation 1s used for the treatment of malaria caused by Plasmodium falciparum or Plasmodium vivax following once daily administration for 3 days.