Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults

Condition(s) targeted: Malaria; Plasmodium Vivax

Intervention: Tafenoquine (Drug); Chloroquine + Primaquine (Drug); tafenoquine (Drug); Chloroquine + Primaquine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: U.S. Army Medical Research and Materiel Command

Official(s) and/or principal investigator(s):
Sornchai Looareesuwan, MD, Principal Investigator, Affiliation: Mahidol University

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.

Official title: A Randomized, Active-control, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Primary outcome: Adequate Clinical Response (ACR).

Secondary outcome:

Efficacy

Safety

Pharmacology

Minimum age: 20 Years. Maximum age: 60 Years. Gender(s): Both.

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.

Bangkok Hospital for Tropical Diseases/Mahidol University, Bangkok 10400, Thailand

Starting date: September 2003
Last updated: April 23, 2015