Conditions: Malaria, Vivax
Keywords: Tafenoquine Plasmodium vivax Hemolysis Primaquine Chloroquine Glucose-6-phosphate dehydrogenase (G6PD) Relapse
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 251
Healthy volunteers: no

Brief summary:
This is a prospective, double-blind, double-dummy, multicenter, comparative study. A total of 300 subjects will be randomized to treatment on Day 1, of which a minimum of 50 female subjects must be enrolled that display moderate glucose-6-phosphate dehydrogenase (G6PD) deficiency (\>=40% - \<70% of the site median G6PD value). Subjects must have a blood smear that is positive for P. vivax at entry. Subjects will be randomized 2:1 to receive tafenoquine (TQ)/chloroquine(CQ) or the active comparator primaquine (PQ)/CQ. All subjects will receive CQ on Days 1 to 3, followed by TQ or PQ and matching placebo beginning on Day 1 or 2. Tafenoquine, or matching placebo, will be given as a single, 300mg dose. Subjects will receive PQ (15mg once daily) or matching placebo for 14 days. The duration of the study is 180 days, including screening and randomization to treatment (Day 1), three in-hospital days (Days 1-3), four out-patient visits while on treatment with study medication (Days 5, 8, 11 and 15) and seven follow-up visits (Days 22, 29, 60, 90, 120, 150 and 180).

The primary safety data collected in this study will help to understand the hemolysis risk to both G6PD-normal and G6PD-deficient subjects. The efficacy data produced from this study will support the results for sister study TAF112582, the pivotal phase III efficacy and safety study of the TQ program.

Detailed description:

Arms:
arm 1: All subjects will receive one of two formulations of CQ from Days 1 to 3 (600 mg \[2×CQ 300 mg\] on Day 1, 600 mg on Day 2 and 300 mg on Day 3, each once daily \[OD\] orally; OR, 620 mg \[4×CQ 155 mg\] on Day 1, 620 mg on Day 2 and 310 mg on Day 3, each once daily \[OD\] orally). Tafenoquine 300mg (2×TQ 150 mg) will be given as a single oral dose on Day 1 or Day 2. Primaquine matching placebo will be given OD orally beginning on Day 1 or Day 2 and continue for 14 days total dosing. All subjects will be followed-up till 180 days. arm 2: All subjects will receive one of two formulations of CQ from Days 1 to 3 (600 mg \[2×CQ 300 mg\] on Day 1, 600 mg on Day 2 and 300 mg on Day 3, each once daily \[OD\] orally; OR, 620 mg \[4×CQ 155 mg\] on Day 1, 620 mg on Day 2 and 310 mg on Day 3, each once daily \[OD\] orally). Primaquine 15mg will be given OD orally beginning on Day 1 or Day 2 and continue for 14 total dosing. Tafenoquine matching placebo will be given as a single oral dose on Day 1 or Day 2. All subjects will be followed-up till 180 days.

Interventions: intervention 1: Tafenoquine intervention 2: Tafenoquine Placebo intervention 3: Chloroquine intervention 4: Primaquine intervention 5: Primaquine Placebo
Intervention descriptions: intervention 1: Tafenoquine will be supplied as a dark pink, capsule-shaped, film-coated tablet that is plain on both sides. Each tablet will contain 150mg TQ. intervention 2: Placebo TQ tablets will be supplied as a dark pink, capsule-shaped, film-coated tablet that is plain on both sides, with common excipients of appropriate quality. intervention 3: One of two formulations of commercially available generic chloroquine may be utilized in this study:

1. tablets containing 500 mg chloroquine phosphate (equivalent to 300 mg chloroquine free base); or,
2. tablets containing 250 mg chloroquine phosphate (equivalent to 155 mg chloroquine free base). intervention 4: Commercially available primaquine containing primaquine phosphate united states pharmacopeia (USP), 26.3 mg (equivalent to primaquine base 15 mg) will be utilized in this study. Primaquine, a pink film-coated tablet imprinted W on one side and P97 on the other side. The PQ tablets for this study have been over-encapsulated in a Swedish orange size B supro capsule. intervention 5: Placebo to match PQ will be supplied as Swedish orange size B supro capsules with common excipients of appropriate quality.

Protocol document: