Clinical Trial: A Pharmacokinetics, Safety and Efficacy Study of Tafenoquine (TQ) in Pediatric Subjects With Plasmodium Vivax (P. Vivax) Malaria

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Open Label, Non-comparative, Multicenter Study to Assess the Pharmacokinetics, Safety and Efficacy of Tafenoquine (SB-252263, WR238605) in the Treatment of Pediatric Subjects With Plasmodium

Brief 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 <16 years of age. A total of 60 subjects will be enrolled. Potential subjects who are slide-positive for P. vivax will be started by the site on chloroquine (CQ) per local/national guidelines. Sites will have up to 48 hours to obtain consent. Once full consent is provided, all subjects will be screened and, if eligible, receive Tafenoquine (TQ), given as a single dose on Day 1. All study medication should be taken with food. After the treatment period, subjects will attend up to 7 follow-up visits through Day 120 (Days 3, 8, 15, 29, 60, 90 and 120). The main cohort will consist of subjects aged >=2 years to <16 years with no restriction on gender. Subjects will be dosed according to four weight bands. Within the total of 60 enrolled pediatric subjects, a second cohort of up to 6 infants aged >=6 months to <2 years (weighing >=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.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Area under the curve from time 0 extrapolated to infinite time (AUC [0-infinity]) of TQ [ Time Frame: Up to Day 120 ]

AUC (0-infinity) will be calculated as dose divided by clearance estimate (CL). AUC (0-infinity) of TQ will be calculated by weight band in pediatric subjects aged >=2 years to <16 years (weighing >=5 kg). PK assessment of AUC (0-infinity) will be assessed at Days 3, 15, 29, 60 and at the time of recurrence. Recurrence is defined by a positive blood smear with or without vivax malaria symptoms.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of participants with gastrointestinal adverse events as measure of safety and tolerability [ Time Frame: Up to Day 120 ]
    Subjects with gastrointestinal adverse events will be evaluated
  • Safety as assessed by clinically relevant drop in hemoglobin (Hb) [ Time Frame: Up to Day 120 ]
    Drop in hemoglobin (Hb) will be assessed
  • Safety as assessed by incidence and severity of adverse events (AEs) [ Time Frame: Up to 120 days ]
    An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
  • Safety as assessed by abnormal laboratory observations [ Time Frame: Up to Day 8 ]
    Laboratory measurements including Hematology and clinical chemistry
  • Number of participants recurrence-free at four months post-dosing to assess efficacy [ Time Frame: Up to 120 days ]
    Recurrence is defined by a positive blood smear with or without vivax malaria symptoms. The estimates of recurrence-free efficacy at Day 120 will be reviewed at each interim and at the final analysis of the study.
  • AUC (0-infinity) of TQ by weight band In infants aged >=6 months to <2 years (weighing >=5 kg) [ Time Frame: Up to Day 120 ]
    AUC(0-infinity) will be calculated as dose divided by clearance estimate (CL). AUC (0-infinity) of TQ will be calculated by weight band In infants aged >=6 months to <2 years (weighing >=5 kg). PK assessment of AUC (0-infinity) will be assessed at Days 3, 15, 29, 60 and at the time of recurrence. Recurrence is defined by a positive blood smear with or without vivax malaria symptoms.


Original Secondary Outcome:

  • Number of participants with gastrointestinal adverse events as measure of safety and tolerability [ Time Frame: Up to Day 120 ]
  • Safety as assessed by clinically relevant drop in hemoglobin (Hb) [ Time Frame: Up to Day 120 ]
  • Safety as assessed by incidence and severity of adverse events (AEs) [ Time Frame: Up to 120 days ]
    An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
  • Safety as assessed by abnormal laboratory observations [ Time Frame: Up to Day 8 ]
    Laboratory measurements including Hematology and clinical chemistry
  • Number of participants recurrence-free at four months post-dosing to assess efficacy [ Time Frame: Up to 120 days ]
    Recurrence is defined by a positive blood smear with or without vivax malaria symptoms. The estimates of recurrence-free efficacy at Day 120 will be reviewed at each interim and at the final analysis of the study.
  • AUC (0-infinity) of TQ by weight band In infants aged >=6 months to <2 years (weighing >=5 kg) [ Time Frame: Up to Day 120 ]
    AUC(0-infinity) will be calculated as dose divided by clearance estimate (CL). AUC (0-infinity) of TQ will be calculated by weight band In infants aged >=6 months to <2 years (weighing >=5 kg). PK assessment of AUC (0-infinity) will be assessed at Days 3, 15, 29, 60 and at the time of recurrence. Recurrence is defined by a positive blood smear with or without vivax malaria symptoms.


Information By: GlaxoSmithKline

Dates:
Date Received: September 10, 2015
Date Started: February 6, 2017
Date Completion: November 22, 2018
Last Updated: April 25, 2017
Last Verified: April 2017