Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults
Condition: Malaria; Plasmodium Vivax
MeSH terms: Malaria
Intervention: Tafenoquine; Chloroquine + Primaquine; tafenoquine; Chloroquine + Primaquine
Intervention description: Tafenoquine: 2 capsules (200mg base/capsule for a total of 400mg base) and 4 chloroquine placebo capsules for 2 days, followed by 2 tafenoquine capsules and 2 chloroquine placebo capsules for 1 day, followed by 1 primaquine placebo capsule/day for 14 days.; Chloroquine (1000 mg chloroquine phosphate) and tafenoquine placebo x 2 day, followed by chloroquine (500 mg chloroquine phosphate) and tafenoquine placebo x 1day, followed by primaquine, 15 mg/day for 14 days.; Tafenoquine (600 mg base) and chloroquine placebo x 1d, chloroquine placebo x 2 days, followed by primaquine placebo for 14 days.; Chloroquine (1000 mg chloroquine phosphate) and tafenoquine placebo x 1 day, followed by chloroquine (1000 mg chloroquine phosphate) x 1 day, followed by chloroquine (500 mg chloroquine phosphate) x 1day, followed by primaquine, 15 mg/day for 14 days.
Intervention MeSH terms: Chloroquine; Chloroquine diphosphate; Primaquine; Tafenoquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Only if Cohort 1 met specified endpoint criteria would Cohort 2 begin enrollment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 70.0
Sex: All
Minimum age: 20 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: malaria; Plasmodium vivax; adults; treatment; tafenoquine

Summary:

      This Phase II study is designed to determine whether a single 600 mg dose or 400mg/day for 3
      days of tafenoquine is efficacious, and well tolerated for clearing P. vivax malaria
      infection (blood schizontocidal and gametocytocidal activity) and preventing P. vivax relapse
      (hypnozoite eradication). It will also further establish the safety and tolerability of these
      doses of tafenoquine.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Positive smear for P. vivax.

          2. Parasite density > 500 and < 200,000/μl

          3. Age: 20-60 years old

          4. Willing to sign consent form

          5. Willing to be hospitalized for 29 days and remain in a malaria free region for 60 days
             thereafter for follow-up.

          6. A female is eligible to enter and participate in this study if she is of:

        a non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
        including any female who is post-menopausal or, b child-bearing potential, has a negative
        pregnancy (urine or serum) test at screen, and agrees to comply with recognized
        contraceptive methods during the treatment stage of the study and for a period of 12 weeks
        after stopping study drug. Recognized contraceptive methods include, abstinence, implants
        of levonorgestrel, injectable progestogen, or appropriate double barrier methods using
        licensed contraceptives such as diaphragm and condom (by the partner) or intrauterine
        device and condom. The use of oral/patch contraceptives during the study is not considered
        sufficient contraceptive protection.

        Exclusion Criteria:

          1. Mixed malaria infections by Field's stain.

          2. Female subjects who are pregnant, lactating or unwilling/unable to comply with
             recognized contraceptive methods during the treatment stage of the study and for a
             period of 12 weeks after stopping study drug.

          3. Symptoms of severe vomiting (no food or inability to take food during the previous 8
             hours).

          4. Demonstrated glucose-6-phosphate dehydrogenase deficiency.

          5. Subject has taken other anti-malarials (mefloquine, primaquine, chloroquine) within
             the past 30 days by history

          6. Clinically significant illness (intercurrent illness e.g. pneumonia, pre-existing
             condition e.g. renal disease, malignancy or conditions that may affect absorption of
             study medication e.g. severe diarrhea or any signs of malnutrition as defined
             clinically).

          7. Clinically significant abnormal laboratory values as determined by history, physical
             examination or routine blood chemistries and hematology values (laboratory guideline
             values for exclusion are hemoglobin <7 gm/dL, platelets < 50,000/μl, White Blood Cell
             count (WBC) < 2000/μl, serum creatinine >2.0mg/dL, or ALT or AST more than 3 times the
             upper limit of normal for age.

          8. History of allergy to chloroquine, mefloquine, tafenoquine, primaquine or any other
             8-aminoquinolines.

          9. Subject has taken another investigational drug within 30 days or 5 half lives
             (whichever is longer), of study start.

         10. History of previous eye surgery or have evidence of corneal or retinal abnormalities
             identified in baseline ophthalmological examination.

         11. Subjects taking concomitant medications likely to affect renal or ophthalmic function
             or that are known to be metabolized primarily by the cytochrome P450 isoforms 3A4/5
             and 2C9 and whose therapeutic effect occurs within a narrow plasma concentration range
             (e.g. warfarin, ketoconazole).

         12. Subjects whom, after examination by the study ophthalmologist, are judged to be at
             risk for acute angle closure glaucoma.

         13. Females who are pre-menarchal.