A Pharmacokinetics, Safety and Efficacy Study of Tafenoquine (TQ) in Pediatric Subjects With Plasmodium Vivax (P. Vivax) Malaria
Condition: Malaria, Vivax
MeSH terms: Malaria; Malaria, Vivax
Intervention: Tafenoquine; Chloroquine
Intervention description: 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).; Subjects may receive chloroquine according to local/national treatment guidelines.
Intervention MeSH terms: Chloroquine; Tafenoquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 6 Months
Maximum age: 15 Years
Healthy volunteers: No
Keywords: pharmacokinetic; pediatric; Tafenoquine; Plasmodium vivax Malaria; G6PD deficiency

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).
    

Eligibility criteria:

        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