Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06666491 | An Interventional Study to Compare the Efficacy and Safety of Tafenoquine (TQ) and Primaquine (PQ) When Either Are Taken Together With Chloroquine (CQ) for the Treatment of P. Vivax Malaria in Indian Participants Aged 2 Years and Older | PHASE3 | RECRUITING | 300 | — | — | Nov 13, 2024 | May 25, 2026 | Aug 7, 2025 | 4 | India |
| NCT02802501 | Efficacy and Safety Study of Tafenoquine (TQ) Co-administered With Dihydroartemisinin-piperaquine (DHA-PQP) for the Radical Cure of Plasmodium Vivax (P. Vivax) Malaria | PHASE3 | COMPLETED | 150 | — | — | Apr 8, 2018 | Aug 19, 2019 | Jul 24, 2020 | 1 | Indonesia |
| NCT02216123 | Study to Assess the Incidence of Hemolysis, Safety, and Efficacy of Tafenoquine (SB-252263, WR238605) Versus Primaquine in Subjects With Plasmodium Vivax Malaria | PHASE3 | COMPLETED | 251 | — | — | Apr 30, 2015 | Nov 4, 2016 | May 16, 2018 | 10 | Brazil, Colombia +4 |
| NCT02563496 | A Pharmacokinetics, Safety and Efficacy Study of Tafenoquine (TQ) in Pediatric Subjects With Plasmodium Vivax (P. Vivax) Malaria | PHASE2 | COMPLETED | 60 | — | — | Feb 6, 2017 | Feb 17, 2020 | Nov 2, 2020 | 4 | Colombia, Vietnam |
| NCT02658435 | Assessment of Any Potential Retinal Effects of Tafenoquine (TQ) | PHASE1 | COMPLETED | 486 | — | — | Feb 2, 2016 | Sep 14, 2017 | Mar 1, 2018 | 3 | United States |
| NCT02184637 | A Study to Evaluate the Pharmacokinetics of a Single Dose of Tafenoquine Co-administered With Either Artemether + Lumefantrine or Dihydroartemisinin + Piperaquine Tetraphosphate | PHASE1 | COMPLETED | 120 | — | — | Jul 31, 2014 | Apr 8, 2015 | Jul 13, 2017 | 1 | United States |
| NCT01928914 | Tafenoquine Thorough QTc Study in Healthy Subjects | PHASE1 | COMPLETED | 260 | — | — | Jul 26, 2011 | Jun 4, 2012 | Jun 12, 2017 | 2 | United States |
Two consecutive negative blood smears between Day 2 and Day 8, no positive blood smear for P. vivax parasites at any point during the 6-month follow-up period, and a negative P. vivax smear at the 6-month assessment.
A participant was considered to have demonstrated relapse-free efficacy at 6 months if: a) Participant had non-zero Plasmodium vivax (P.vivax) asexual parasite count at Baseline (Day 1), b) Participant demonstrated initial clearance of P.vivax parasitemia, c) Participant had no positive asexual P.vivax parasite count at any assessment prior to or on study Day 180 following initial parasite clearance, d) Participants did not take a concomitant medication with anti-malarial activity (excluding study treatment) at any point between Study Day 1 and their last parasite assessment, e) Participant was parasite-free at 6 months. The percentage of participants who were relapse-free at 6 months post dose has been presented.
Clinically relevant hemolysis is defined as a decrease in hemoglobin of \>=30% or \>3 grams per deciliter (g/dL) from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL at any visit after the first dose of study medication. The percentage of participants with clinically relevant hemolysis has been summarized. Safety Population comprised of all randomized participants who received at least one dose of blinded study medication.
Clinically relevant hemolysis is defined as a decrease in hemoglobin of \>=30% or \>3 g/dL from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL at any visit after the first dose of study medication. Despite additional efforts, no females with moderate G6PD-deficiency were enrolled that experienced clinically-significant hemolysis during the study; hence, the end point could not be estimated.
Blood samples were collected at indicated time points for pharmacokinetic analysis of tafenoquine. Pharmacokinetic parameters were determined using standard non-compartmental methods. AUC(0-infinity) of tafenoquine was evaluated for participants aged \>=2 years to \<16 years (weighing \>=5 kg). Pharmacokinetic (PK) population consisted of all participants with at least one PK sample taken at Days 3, 15, 29 and 60, with accurate dosing and sample time histories.
The change from baseline will be assessed as a binomial output as, Yes or No. Spectral domain OCT (SD-OCT) images/scan will be obtained. For Central subfield thickness and Central retinal lesion thickness, change from baseline of at least 40 microns (µ) will be consider 'Yes'. Central Retinal Lesion Thickness is defined as the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris measured in the central 1millimeter (mm) of the centre scan
The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Total Macular Volume, change from baseline of 10% will be considered 'Yes'
The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Ellipsoid zone disruption will be assessed by manual reading
The change from baseline will be assessed as a binomial output as, Yes or No. SD-OCT images/scan will be obtained. Abnormal auto-fluorescence will be assessed by FAF by manual reading
Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.
Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.
Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.
Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.
Contineous QTcF will be electronically recorded using holtor monitors. The primary comparison of interest is the mean time-matched change from baseline in QTcF for the difference tafenoquine-placebo for 1200mg dose of tafenoquine at each timepoint.
| Arm | Type | Description |
|---|---|---|
| TQ/CQ | EXPERIMENTAL | Participants in this group receive a single dose of TQ on Day 1 or Day 2 and a single dose of CQ daily, on Days 1 to 3. |
| PQ/CQ | ACTIVE_COMPARATOR | Participants in this group receive a single dose of PQ daily from Day 1 or 2, up to Day 14 (or Day 15 if PQ started on Day 2) and a single dose of CQ daily, on Days 1 to 3. |
| DHA-PQP plus tafenoquine 300 mg single dose | EXPERIMENTAL | Subjects will receive open label DHA-PQP, 3 or 4 tablets per day (according to the body weight) from Day 1 to Day 3. They will receive double-blind 300 mg single dose of tafenoquine (TQ) on Day 1 and matched-placebo for primaquine (PQ) from Day 1 to Day 14. |
| DHA-PQP plus primaquine 15 mg for 14 days | ACTIVE_COMPARATOR | Subjects will receive open label DHA-PQP, 3 or 4 tablets per day (according to body weight) from Day 1 to Day 3. They will receive double-blind 15 mg primaquine (PQ) from Day 1 to Day 14 and matched-placebo for tafenoquine (TQ) on Day 1. |
| DHA-PQP alone (placebo arm) | PLACEBO_COMPARATOR | Subjects will receive open label DHA-PQP, 3 or 4 tablets per day (according to body weight) from Day 1 to Day 3. They will receive double-blind matched-placebo for tafenoquine (TQ) on Day 1 and matched-placebo for primaquine (PQ) from Day 1 to Day 14. |
| Tafenoquine+ Chloroquine | EXPERIMENTAL | 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. |
| Primaquine+ Chloroquine | EXPERIMENTAL | 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. |
| Tafenoquine 50 mg | EXPERIMENTAL | Subjects with weight band of \>=5 to \<=10 kilogram (kg) will receive 50 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines. |
| Tafenoquine 100 mg | EXPERIMENTAL | Subjects with weight band of \>10 to \<=20 kg will receive 100 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines. |
| Tafenoquine 150 mg | EXPERIMENTAL | Subjects with weight band of \>10 to \<=20 kg will receive 150 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines. |
| Tafenoquine 200 mg | EXPERIMENTAL | Subjects with weight band of \>20 to \<=35 kg will receive 200 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines. |
| Tafenoquine 300 mg | EXPERIMENTAL | Subjects with weight band of \>35 kg will receive 300 mg tafenoquine on Day 1. Subject may receive CQ per local/national guidelines. |
| Tafenoquine 300 milligram (mg) single dose | EXPERIMENTAL | Participants will receive single dose of TQ (2 tablets of 150mg) after standard meal. Participant will be randomized in a 2:1 ratio to 300mg TQ (n=300) or matched-placebo (n=150). |
| Matched Placebo 300mg single dose | PLACEBO_COMPARATOR | Participants will receive single dose of matched placebo (2 tablets of 150mg) after standard meal. Participant will be randomized in a 2:1 ratio to 300mg TQ (n=300) or matched-placebo (n=150). |
| Cohort 1- TQ w/DHA+PQP | EXPERIMENTAL | Tafenoquine (TQ) will be co-administered with Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) on Day 1. DHA+PQP alone will be administered at 24 hours (h) (Day 2) and 48 h (Day 3) post first dose administration. |
| Cohort 2 - TQ w/AL | EXPERIMENTAL | Tafenoquine co-administered with Artemether + Lumefantrine (AL) on Day 1. AL alone will be administered at 8h (Day 1), 24h and 36h (Day 2), 48h and 60 h (Day 3) post first dose administration. |
| Cohort 3 - DHA+PQP alone | EXPERIMENTAL | Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) will be administered on Day 1 and at 24 hours (Day 2) and 48 hours (Day 3) post first dose administration |
| Cohort 4 - AL alone | EXPERIMENTAL | Artemether + Lumefantrine will be administered on Day 1 and 8h, 24 and 36h (Day 2), 48h and 60 h(Day 3) post first dose administration |
| Cohort 5 - TQ alone | EXPERIMENTAL | A single dose of Tafenoquine will be administered on Day 1 |
| Group 1 | PLACEBO_COMPARATOR | Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on three consecutive days of dosing |
| Group 2 | EXPERIMENTAL | Subjects in group 2 receive 400mg of tafenoquine and placebo for moxifloxacin on three consecutive days of dosing |
| Group 3 | ACTIVE_COMPARATOR | Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on days 1 and 2. On day 3, subjects receive placebo for tafenoquine and 400mg moxifloxacin. |
| Group 4 | EXPERIMENTAL | Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on days 1 and 2. On day 3, subjects receive placebo for moxifloxacin and 300mg of tafenoquine |
| Group 5 | EXPERIMENTAL | Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on days 1 and 2. On day 3, subjects receive placebo for moxifloxacin and 600mg of tafenoquine |
| Name | Type | Description |
|---|---|---|
| Tafenoquine | DRUG | A single dose of TQ will be administered orally on Day 1 or Day 2. |
| Primaquine | DRUG | A single dose of PQ will be administered orally, daily, on Day 1 or 2 to Day 14 (or Day 15 if PQ started on Day 2). |
| Chloroquine | DRUG | A single dose of CQ will be administered orally, daily, on Days 1 to 3. |
| Matched-Placebo for Tafenoquine | DRUG | This intervention contains tafenoquine matched-placebo. Two tablets of this formulation will be administered orally with water as a single dose after a meal. Dose will be taken at least 3 hours after DHA-PQP. |
| Matched-Placebo for Primaquine | DRUG | This intervention contains primaquine matched-placebo. One capsule of this formulation will be administered orally with water as a single dose after a meal for 14 days. Dose will be taken at least 3 hours after DHA-PQP (Days 1, 2 and 3). |
| Dihydroartemisinin-piperaquine (DHA-PQP) | DRUG | This formulation is provided as tablet containing 320 mg of piperaquine tetrasphosphate (as the tetrahydrate; PQP) and 40 mg dihydroartemisinin (DHA). This tablet will be administered orally as single dose for 3 days. For subjects weighing \<75 kg, 3 tablets will be administered per day. For subjects weighing \>=75 kg, 4 tablets will be administered per day. Dose will be taken at least 3 hours after last food intake. No food will be allowed for at least 3 hours after dosing. |
| ACT plus PQ (Rescue medication) | DRUG | Subjects with relapse during the 180 day follow up period will be given an ACT plus PQ 0.5 mg/kg for 14 days as rescue medication. |
| PQ (End of study treatment) | DRUG | Subjects who do not relapse during the study will receive PQ 0.5mg/kg for 14 days at the end of the study. |
| Tafenoquine Placebo | DRUG | 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. |
| Primaquine Placebo | DRUG | Placebo to match PQ will be supplied as Swedish orange size B supro capsules with common excipients of appropriate quality. |
| Tafenoquine 150 mg | DRUG | Tablet contains TQ as tafenoquine succinate. The 2 tablets (2 tablets of 150mg) of dark pink, capsule-shaped, film coated will be administered orally with 240ml of water. |
| Matched placebo 150mg | DRUG | It is the matched Placebo tablet. The 2 tablets (2 tablets of 150mg) of dark pink, capsule-shaped, film coated will be administered orally with 240ml of water. |
| Dihydroartemisinin + Piperaquine tetraphosphate | DRUG | White, oblong, biconvex, film-coated tablet with a break-line and marked on one side with two "σ" letters containing 320 mg piperaquine tetraphosphate (as the tetrahydrate; PQP) and 40 mg dihydroartemisinin (DHA). To be administered orally |
| Artemether + Lumefantrine | DRUG | Light yellow, round tablet with "NC" debossed on one side and "CG" on the other, containing 20 mg artemether and 120 mg lumefantrine. To be administered orally |
| Tafenoquine 300mg | DRUG | Single dose of Tafenoquine give on Day 3 only |
| Tafenoquine 600mg | DRUG | Single dose of Tafenoquine given on Day 3 only |
| Tafenoquine 1200mg | DRUG | 400mg Dose of Tafenoquine given on each of the three consecutive dosing days |
| moxifloxacin | DRUG | moxifloxacine given on Day 3 only |
| Placebo for Tafenoquine | DRUG | Placebo given on all three days to all groups except for group 5 on Day 3 |
| Placebo for moxifloxaxin | DRUG | Placebo for moxifloxacin, given to all groups on all days except for Group 3 on Day 3 |
Inclusion Criteria: 1. Males and females \>=2 years of age and under (\<) 65 years of age, weighing \>10 kg. 2. The participant has a positive malarial smear for P. vivax with a parasite density of \>100/microliter and \<100,000/microliter. 3. The participant has a screening Hb value \>8 g/dL. 4. T...