Phase III trial of FDC of arterolane maleate and PQP tablets in patients with acute uncomplicated Plasmodium vivax malaria

Phase 3

Completed

• Conditions: Acute uncomplicated Plasmodium vivax malaria

• Registration Number: CTRI/2011/11/002129
• Lead Sponsor: Ranbaxy Laboratories Limited

Brief Summary

The proposed Phase III study is an open label, randomized, parallel group, multicentric trial comparing the safety and efficacy of FDC tablets of arterolane maleate and piperaquine phosphate with chloroquine tablets in patients with acute uncomplicated *Plasmodium vivax* malaria.

The study protocol (Study number: R2011005) submitted to the DCGI on 30 June 2011.

xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /The study is planned to be initiated at 3-5 sites in India in the month of September/October 2011.

Approximately 316 patients will be enrolled into the study to provide 284 evaluable patients in 1:1 ratio (142 evaluable patients each in arterolane maleate + piperaquine and chloroquine arms).

Informed consent will be obtained from all patients before enrolling them in the study.Patients will be screened as per the inclusion/ exclusion criteria according to the study protocol and will be randomly assigned to one of the two treatment groups:

 1. Fixed dose combination (FDC) tablets of arterolane maleate 150 mg  and PQP 750 mg; 3 doses (total of 3 tablets) of Ranbaxy Laboratories

Limited, xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" /India for oral administration over 3 days

or

2. Chloroquine tablets (a total dose of 2.5 g chloroquine phosphate equivalent to 1.5 g base), each tablet containing 250 mg of chloroquine phosphate USP, equivalent to 150 mg of chloroquine base; 4 doses (total of 10 tablets of 250 mg each) of Bayer for oral administration over 3 days

One tablet of 26.3 mg (equivalent to 15 mg base) of primaquine phosphate of Ipca Laboratories Limited, India for oral administration will be provided to the study patients for consuming it over 14 consecutive days (one tablet/day) i.e. starting on Day 3/ Day of discharge following the 3-day treatment period as an anti-relapse measure. Medication compliance cards will be issued to all enrolled patients to monitor primaquine compliance.

The  Primary objective of the study is to compare the proportion of aparasitemic and afebrile patients at 72 hours in the two treatment groups.

Patients’ participation will be for atleast 42(±2) days following the first dose of study medication. Patients will be hospitalized for at least 3 days (Days 0, 1 and 2) and will be discharged from the study site on Day 3.The patient will return to the study site for follow up visits on Days 7(±1), 14(±1), 21(±2),  28(+2), 35 (±2) and 42(±2) / end of study, or on any day if the patient spontaneously returns with fever.

Blood Sampling for Pharmacokinetic Analysis will be done as per the protocol for enrolled patients.

All AEs reported from the time of study medication administration until end of study visit i.e. Day 42 will be recorded, whether elicited or spontaneously reported by the patient. Adverse events will be evaluated by the Investigator as per CTCAE/ CTEP.

Patients who are considered to be treatment failures will be withdrawn from the study and given rescue treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-17
• Last Update Posted: 2013-02-21

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 316

Inclusion Criteria

• Patients must fulfill the following inclusion criteria to be eligible for enrollment into the study: 1.Body weight must be > 40 kg at screening.
• 2.Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P.
• vivax parasites only.
• 3.Parasite density appropriate for inclusion will be > 250/ µL of blood.
• 4.Presence of fever (axillary temperature ≥ 37.5 °C or oral ≥ 38 °C) or history of fever in the past 48 hours.
• 5.Female patients, if of child-bearing potential must be non-lactating and willing to use contraceptive methods during the study period.
• 6.Patients willing to give informed consent.
• Patients <18 years, wherever feasible to the extent of the patient’s capabilities willing to provide informed assent and their parent/legal acceptable representative willing to provide informed consent.
• 7.Willingness and ability to comply with the study protocol for the duration of the study.
• 8.Patient resides within a reasonable distance of the investigational site, so that attendance of all study visits and follow-up by medical staff are logistically feasible.

Exclusion Criteria

• If any of the following conditions apply, the patient should not be enrolled in the study: 1.Patients with severe malaria as per WHO criteria 1, 17 (Appendix B).
• 2.Mixed infection with another Plasmodium species at the time of presentation (including P.
• falciparum, P.
• ovale and P.
• 3.Hemoglobin (Hb) level of 8 gm/dL.
• 4.Past history of hemolytic anaemia or methemoglobinemia.
• 5.A female patient who is lactating or pregnant at screening.
• 6.Known allergy to artesunate, artemisinin derived products, piperaquine, chloroquine, primaquine or any other related drugs.
• 7.Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhea defined as 3 episodes of watery stools in the previous 24 hours or patients who have had 3 episodes of vomiting within 24 hours prior to screening).
• 8.Use of concomitant medications that may induce haemolysis or haemolytic anaemia or depressants of myeloid element of the bone marrow.
• 9.Any antimalarial treatment during 1 month prior to screening, as assessed by medical history.
• 10.Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole.
• 11.Participation in any investigational drug study at least 3 months prior to screening.
• 12.Any other underlying disease that may compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis, bacterial infection; cardiac or pulmonary disease).
• 13.Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management.
• These abnormalities include QTc interval 450 msec at screening and cardiac conduction disorders, with the exception of right bundle branch block.
• 14.Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at screening: „XSerum creatinine 1.5 ¡Ñ upper limit of normal (ULN) „XAspartate transaminase 2.5 ¡Ñ ULN „XAlanine transaminase 2.5 ¡Ñ ULN „XSerum bilirubin 3 mg/dL 15.Patients who have had a splenectomy as confirmed by history or clinical examination.
• 16.Patients with known history of human immunodeficiency virus (HIV) infection or other immunosuppressive disorders.
• 17.Evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) that may compromise the diagnosis and the evaluation of the response to the study medication.
• 18.Patients who have epilepsy or a history of convulsions.
• 19.Patients who are G6PD deficient indicated by laboratory investigation at screening.
• 20.Any retinal/ visual field defects or auditory defects, of any etiology assessed on the basis of history.
• 21.Patients with psoriasis and porphyria assessed on the basis of history.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of aparasitemic and afebrile patients at 72 hours	72 hours

Secondary Outcome Measures

Name	Time	Method
Cure rate	Day 28
Parasite clearance time (PCT)	Hours
Fever clearance time (FCT)	Hours

Trial Locations

Locations (4)

Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Department of Medicine, BYL Nair Charitable Hospital & TN Medical College; 🇮🇳 Mumbai, MAHARASHTRA, India

Department of Medicine, SP Medical College and Associated Group of Hospitals; 🇮🇳 Bikaner, RAJASTHAN, India

Department of Pharmacology, Calcutta School of Tropical Medicine; 🇮🇳 Kolkata, WEST BENGAL, India

Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital

🇮🇳Mumbai, MAHARASHTRA, India

Dr Nithya Gogtay

Principal investigator

912224174420

njgogtay@hotmail.com