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

NCT02563496 | Completed Phase 2 Results

• 1 other identifier: 113577
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 4

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 in order to identify appropriate doses that achieve a similar exposure to that of the TQ adult dose of 300 milligram (mg).

Conditions

Malaria, Vivax

Keywords

pharmacokinetic; pediatric; Tafenoquine; Plasmodium vivax Malaria; G6PD deficiency

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Days 3, 15, 29 and 60 post dose

Secondary Outcomes (7)

• Number of Participants With Gastrointestinal Adverse Events

  Up to Day 120

• Number of Participants With Hemoglobin Decline From Baseline Over First 10 Days

  Baseline and up to Day 10

• Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

  Up to Day 120

• Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

  Baseline (Day 1) and up to Day 8

• Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

  Baseline (Day 1) and up to Day 8

Study Arms (5)

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.

Drug: Tafenoquine; Drug: Chloroquine

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.

Drug: Tafenoquine; Drug: Chloroquine

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.

Drug: Tafenoquine; Drug: Chloroquine

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.

Drug: Tafenoquine; Drug: Chloroquine

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.

Drug: Tafenoquine; Drug: Chloroquine

Interventions

Tafenoquine DRUG

Tafenoquine tablet is supplied as film-coated tablet (100 mg, 150 mg, 200 mg and 300 mg) and fast-dispersing film coated tablet (50 mg).

Tafenoquine 100 mg; Tafenoquine 150 mg; Tafenoquine 200 mg; Tafenoquine 300 mg; Tafenoquine 50 mg

Chloroquine DRUG

Subjects may receive chloroquine according to local/national treatment guidelines.

Tafenoquine 100 mg; Tafenoquine 150 mg; Tafenoquine 200 mg; Tafenoquine 300 mg; Tafenoquine 50 mg

Eligibility Criteria

• Age: 6 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Medicines for Malaria Venture: collaborator

Study Sites (4)

GSK Investigational Site

Montería, Colombia

Location

GSK Investigational Site

Hanoi, 100000, Vietnam

Location

GSK Investigational Site

Ho Chi Minh City, 700000, Vietnam

Location

GSK Investigational Site

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• Velez ID, Hien TT, Green JA, Martin A, Sharma H, Rousell VM, Breton JJ, Ernest TB, Rolfe K, Taylor M, Mohamed K, Jones SW, Chau NH, Hoa NT, Duparc S, Tan LK, Goyal N. Tafenoquine exposure assessment, safety, and relapse prevention efficacy in children with Plasmodium vivax malaria: open-label, single-arm, non-comparative, multicentre, pharmacokinetic bridging, phase 2 trial. Lancet Child Adolesc Health. 2022 Feb;6(2):86-95. doi: 10.1016/S2352-4642(21)00328-X. Epub 2021 Dec 3.

  PMID: 34871570 DERIVED

MeSH Terms

Conditions

Malaria, Vivax; Glucosephosphate Dehydrogenase Deficiency

Interventions

tafenoquine; Chloroquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: September 30, 2015
• Study Start: February 6, 2017
• Primary Completion: December 15, 2019
• Study Completion: February 17, 2020
• Last Updated: November 2, 2020
• Results First Posted: November 2, 2020

Record last verified: 2020-10

Locations

CO (1); VN (3)