Study to evaluate the efficay, safety and tolerability of tafenoquine in subject with Plasmodium vivax malaria

Phase 2/3

Active, not recruiting

• Conditions: Malaria with Plasmodium vivax

• Registration Number: CTRI/2012/03/002511
• Lead Sponsor: GlaxoSmithKline Pharmaceuticals Ltd

Brief Summary

Tafenoquine is a new 8-aminoquinoline antimalarial drug being co-developed by GlaxoSmithKline and the Medicines for Malaria Venture with the assistance and historic support of the Walter Reed Army Institute of Research for the radical cure of acute P. vivax malaria in combination with standard doses of chloroquine (CQ). TQ has been shown to be well-tolerated in the treatment and prevention of asmodial infections in pre-clinical models and during Phase 1, 2 and 3 clinical studies in >3000 subjects. Of note, TQ possesses activity against all stages of the Plasmodium lifecycle, including the dormant P. vivax hypnozoite. This study (TAF112582) will be conducted to select an efficacious and well-tolerated TQ dose (Part1) to be co-administered with CQ. Part 2 will investigate the selected TQ/CQ regimen and its safety and efficacy in the treatment and radical cure of P. vivax malaria.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-17
• Last Update Posted: 2013-07-16

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: All
• Target Recruitment: 924

Inclusion Criteria

• Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the IB/IB supplement(s), and locally approved prescribing information for CQ and PQ.
• Subjects eligible for enrolment in the study must meet all of the following criteria: Positive Giemsa smear for P.
• vivax Parasite density >100 and <100000 Age: ≥16 years A female is eligible to enter and participate in this study if she is non-pregnant, non-lactating and if she is of: non-child bearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or <6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL), pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation with medical report verification, negative pregnancy test or, child-bearing potential, has a negative pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study drug: Use of oral contraceptive, either combined or progestogen alone used in conjunction with double barrier method as defined below Use of an intrauterine device with a documented failure rate of <1% per year Double barrier method consisting of spermicide with either condom or diaphragm Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female.
• Complete abstinence from intercourse for 2 weeks prior to administration of study drug, throughout the study and for a period of 90 days after stopping study drug.
• A signed and dated informed consent is obtained from the subject or the subject’s legal representative prior to screening.
• NB Assent is obtained from subjects <18 years, where applicable and written or oral witnessed consent has been obtained from parent or guardian.
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned Willing to be hospitalized for 3 days and return to clinic for all follow-up visits including Day 180 QTc <450 msec at screening based on a single QTcF value at screening or as an average of triplicate ECGs obtained over a brief recording period by machine or manual over-read if first is greater than 450 msec.

Exclusion Criteria

• Subjects meeting any of the following criteria must not be enrolled in the study: Mixed malaria infections (e.g. identified by Giemsa-stained smear or rapid diagnostic test) Severe vivax malaria as defined by WHO criteria.
• Severe vomiting (no food or inability to take food during previous 8 hours) Screening haemoglobin (Hb) concentration 7 g/dL.
• Glucose 6-phosphate dehydrogenase deficiency, assessed by a quantitative spectrophotometric phenotype assay: Males: Any subject with an enzyme level 70% of the site median value for G6PD normals will be excluded.
• Females: (i) Those females with a screening Hb ≥ 10 g/dL will only be excluded if their enzyme level is 70% of the site median value for G6PD normals.
• Those females with Hb ≥7 but 10 g/dL will be excluded if an enzyme level is not 90% of the site median value for G6PD normals.
• Liver function test ALT 2 x ULN.
• Any clinically significant concurrent illness (e.g. pneumonia, septicaemia), pre-existing conditions (e.g. renal disease, malignancy), conditions that may affect absorption of study medication (e.g. vomiting or severe diarrhoea) or clinical signs and symptoms of severe cardiovascular disease (e.g. uncontrolled congestive heart failure or severe coronary artery disease).
• These abnormalities may be identified on the screening history and physical or laboratory examination Subject has taken antimalarials (e.g. ACT, mefloquine, primaquine, chloroquine) or drugs with anti-malarial activity within the past 30 days by history.
• History of allergy to chloroquine, mefloquine, tafenoquine, primaquine or to any other 4- or 8-aminoquinolines.
• Any contraindications to chloroquine or primaquine administration including a history of porphyria, psoriasis or epilepsy (please refer to chloroquine and primaquine locally approved prescribing information).
• Subject who has previously received study medication for this protocol (all parts) or has received treatment with any other investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• History of illicit drug abuse or heavy alcohol intake within 6 months of the study.
• Subjects who have taken or will likely require the use of medications from the prohibited medication list (see Appendix 5) which include the following classes: Histamine-2 blockers and antacids.
• Drugs known to prolong the QTc interval.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Relapse efficacy	Relapse efficacy six months post-dosing

Secondary Outcome Measures

Name	Time	Method
Relapse efficacy	Relapse efficacy four months post-dosing
Parasite Clearance Time	Time needed to clear asexual parasite from the
Fever Clearance Time	Time from first dose of treatment to the time
Time to relapse	Six months post- dosing

Trial Locations

Locations (7)

Kothari Medical And Research Institute; 🇮🇳 Bikaner, RAJASTHAN, India

Krishna Institute of Medical Sciences; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

M.V. Hospital And Research Centre; 🇮🇳 Lucknow, UTTAR PRADESH, India

National Institute of Malaria Research; 🇮🇳 Delhi, DELHI, India

S.P. Medical College & A.G. Hospitals; 🇮🇳 Bikaner, RAJASTHAN, India

Sri Ramchandra Medical Centre; 🇮🇳 Chennai, TAMIL NADU, India

Wenlock District Government Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Kothari Medical And Research Institute

🇮🇳Bikaner, RAJASTHAN, India

Dr Dhanpat K Kochar

Principal investigator

drdkkochar@yahoo.com