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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02563496
Recruitment Status : Completed
First Posted : September 30, 2015
Last Update Posted : March 23, 2020
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE September 10, 2015
First Posted Date  ICMJE September 30, 2015
Last Update Posted Date March 23, 2020
Actual Study Start Date  ICMJE February 6, 2017
Actual Primary Completion Date December 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2015)
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 Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
  • 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 Measures  ICMJE
 (submitted: September 28, 2015)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pharmacokinetics, Safety and Efficacy Study of Tafenoquine (TQ) in Pediatric Subjects With Plasmodium Vivax (P. Vivax) Malaria
Official Title  ICMJE 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 Vivax Malaria
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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malaria, Vivax
Intervention  ICMJE
  • Drug: Tafenoquine
    Tafenoquine tablet is supplied as film-coated tablet (150 mg) and fast-dispersing film coated tablet (50 mg)
  • Drug: Chloroquine
    Subjects will receive chloroquine according to local/national treatment guidelines
Study Arms  ICMJE Experimental: Tafenoquine + Chloroquine
Two formulations of TQ will be made available; a 150 milligram (mg) film-coated tablet (TQ adult tablet), and a 50mg fast-dispersing film coated tablet (TQ pediatric tablet). Subjects will receive single oral dose of TQ based on their weight on Day 1, co-administered with CQ. There will be four weight bands of >=5 to <=10 kg, >10 to <=20 kg, >20 to =<35 kg and >35 kg with proposed starting doses for pediatrics from 100 to 300 mg TQ. Subjects with >35 kg weight will receive the TQ adult tablet. Subject will receive CQ per local/national guidelines.
Interventions:
  • Drug: Tafenoquine
  • Drug: Chloroquine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 28, 2015)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 17, 2020
Actual Primary Completion Date December 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject is >=2 years to <16 years of age at the time of signing of the assent and/or informed consent. An additional cohort of subjects aged >=6 months to <2 years may be recruited following the first interim analysis.
  • The subject has a positive malarial smear for P. vivax.
  • The subject has a history of fever within 48 hours prior to enrollment.
  • The subject has a glucose 6-phosphate dehydrogenase (G6PD) value (measured by a quantitative spectrophotometric phenotype assay) >=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 <1% per year; Use of depo provera injection; Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female.
  • The subject and/or the subject's parent(s)/legal guardian(s) agree to G6PD genotyping in the context of a subsequent hemolytic anemia AE.
  • The subject and parent(s)/legal guardian(s) are willing and able to comply with the study protocol.
  • In accordance with regional/local laws and regulations, the parent(s)/legal guardian(s) has given written informed, dated consent; and the subject has given written assent, if applicable, to participate in the study.

Exclusion Criteria:

  • The subject has a mixed malaria infection (identified by a malarial smear or rapid diagnostic test).
  • The subject has a condition that may affect absorption of study medication, such as severe vomiting (no food or inability to take food during the previous 8 hours).
  • The subject has a liver alanine aminotransferase (ALT) >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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Colombia,   Vietnam
Removed Location Countries Thailand
 
Administrative Information
NCT Number  ICMJE NCT02563496
Other Study ID Numbers  ICMJE 113577
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Medicines for Malaria Venture
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP