Ph 2B/3 Tafenoquine (TFQ) Study in Prevention of Vivax Relapse

• Status: Completed
• Trial end date: 2016-11-18
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this two part study is to test the safety and efficacy of Tafenoquine (with Cholorquine) as a radical cure for Plasmodium vivax (P.vivax) malaria relative to the control Chloroquine.Part 1 aims to select an efficacious and well tolerated dose that can be co-administered with Chloroquine. Part 2 will investigate the safety and efficacy of the selected dose (300 mg tafenoquine) in the treatment and radical cure of Plasmodium Vivax Malaria.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Collaborator: Medicines for Malaria Venture
• Treatments: Chloroquine; Chloroquine diphosphate; Primaquine; Tafenoquine

Criteria

Inclusion Criteria: - Positive Giemsa smear for P. vivax

• Parasite density >100 and <200,000/μL

• ≥16 years

• A female is eligible if she is non-pregnant, nonlactating 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 follicle stimulating hormone >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 serum 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

• Use of depo provera injection (part 2)

• 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 (part 1 only) or as an average of triplicate Electrocardiogram obtained over a brief recording period by machine or manual over-read if first is >450 msec.- Exclusion Criteria: - Mixed malaria infections (e.g. identified by Giemsa-stained smear or rapid diagnostic test)

• Severe vivax malaria as defined by World Health Organisation criteria.

• Severe vomiting (no food or inability to take food during previous 8 hours)

• Screening haemoglobin concentration <7 g/dL.

• Glucose 6-phosphate dehydrogenase deficiency, assessed by a quantitative spectrophotometric phenotype assay:

Part 1 - Males: Any subject with an enzyme level <70% of the site median value for Glucose 6-phosphate dehydrogenase normals will be excluded. Females: 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 Glucose 6-Phosphate dehydrogenase normals. hose females with Hb ≥7 but < 10 g/dL will be excluded if an enzyme level is not > 90% of the site median value for Glucose 6-Phosphate dehydrogenase normals.

Part 2 - Any subject with enzyme level <70% of the site median value for Glucose 6-phosphate dehydrogenase normals will be excluded

• Liver function test alanine transaminase >2x Upper Limit of Normal

• 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 diarrhea) 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 which include the following classes: Histamine-2 blockers and antacids.

• Drugs with haemolytic potential.

• Drugs known to prolong the QTc interval