Phase 2
N=60
A Pharmacokinetics, Safety and Efficacy Study of Tafenoquine (TQ) in Pediatric Subjects With Plasmodium Vivax (P. Vivax) Malaria
Malaria, Vivax
Bottom Line
View on ClinicalTrials.gov: NCT02563496 ↗Enrolled (actual)
60
Serious AEs
1.7%
Results posted
Nov 2020
Primary outcome: Primary: Area Under the Curve From Time 0 Extrapolated to Infinite Time (AUC[0-infinity]) of Tafenoquine by Weight Band in Participants Aged >=2 Years to <16 Years (Weighing >=5 kg) — 85.1; 154.7; 111.4; 120.8 Hours*microgram per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tafenoquine (Drug); Chloroquine (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Curve From Time 0 Extrapolated to Infinite Time (AUC[0-infinity]) of Tafenoquine by Weight Band in Participants Aged >=2 Years to <16 Years (Weighing >=5 kg) |
85.1; 154.7; 111.4; 120.8 | — |
| SECONDARY Number of Participants With Gastrointestinal Adverse Events |
2; 3; 1; 6; 0; 0 | — |
| SECONDARY Number of Participants With Hemoglobin Decline From Baseline Over First 10 Days |
14; 5; 21; 19; 0; 0 | — |
| SECONDARY Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) |
10; 4; 10; 13; 0; 0 | — |
| SECONDARY Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 0; 12; 4 | — |
| SECONDARY Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 0; 14; 5 | — |
| SECONDARY Number of Participants With Relapse-Free Efficacy at 4 Months |
12; 4; 20; 17 | — |
| SECONDARY AUC(0-infinity) of Tafenoquine by Weight Band in Participants Aged >=6 Months to <2 Years (Weighing >=5 kg) |
— | — |
Summary
This is a prospective, open-label, multicenter, non-comparative, single arm study of pediatric subjects with Plasmodium vivax (P. vivax) malaria, aged 6 months to =2 years to =6 months to =5 kilogram [kg]) will be recruited following completion of a planned first interim analysis. An interim analysis will be conducted once sufficient data from 16 subjects is available to assess pharmacokinetic (PK) and safety parameters. If needed, a second interim analysis will be conducted after a total of 32 subjects have enrolled. The primary objective of this PK bridging study is to adequately characterize the systemic TQ exposure in the pediatric population in order to identify appropriate doses that achieve a similar exposure to that of the TQ adult dose of 300 milligram (mg).
Eligibility Criteria
Inclusion Criteria
- Subject is >=2 years to =6 months to =70% of the site median value for G6PD normal adult males.
- The subject has a screening Hb value >=8 gram per decilitre (g/dL).
- The subject has a body weight >=5 kg.
- Males and females are eligible to enter the study. A female is eligible to enter and participate in this study if she is non-pregnant, non-lactating and if she is of: Non-childbearing potential (i.e., premenstrual); 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 medication: Complete abstinence from intercourse for 2 weeks prior to administration of study medication, throughout the study and for a period of 90 days after stopping study medication; Use of combined oral contraceptive consisting of spermicide with either condom or diaphragm; Use of intrauterine device with a documented failure rate of 2 time the upper limit of normal (ULN).
- The subject has a clinically significant concurrent illness (for example; pneumonia, meningitis, septicaemia, coagulopathy, severe hemorrhage), pre-existing condition (e.g., renal disease, malignancy, malnutrition, known pre-existing human immunodeficiency virus [HIV]), febrile convulsions prior to consent, or clinical signs and symptoms of severe cardiovascular disease (for example; congenital heart disease).
- The subject has a history of porphyria, psoriasis, or epilepsy.
- The subject has taken anti-malarials (for example; artemisinin-based combination therapies, mefloquine, primaquine, or any other 4- or 8-aminoquinoline) or drugs with antimalarial activity within 30 days prior to study entry.
- The subject has received treatment with any investigational drug within 30 days of study entry, or within 5 half-lives, whichever is longer.
- The subject has taken or will likely require during the study the use of: histamine-2 blockers, antacids, anti-diabetic drugs of the biguanide class (i.e., phenformin, buformin), anti-arrhythmic agents dofetilide, procainamide, pilsicainide.
- The subject has a serum creatinine above the ULN and is currently taking metformin.
- The subject has a history of allergy or intolerance to chloroquine, mefloquine, tafenoquine, primaquine, or to any other 4- or 8-aminoquinoline.
- The subject has previously enrolled in this study.
- The subject has severe P. vivax malaria as defined by world health organization (WHO) criteria
Data sourced from ClinicalTrials.gov (NCT02563496). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.