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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01290601
First received: February 3, 2011
Last updated: NA
Last verified: February 2011
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Malaria
Vivax Malaria
Drug: Tafenoquine
Drug: Chloroquine + Primaquine
Drug: tafenoquine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Adequate Clinical Response (ACR). [ Designated as safety issue: No ]
    Day 28 cure rate. A subject will be considered a success (cure) if they have an Adequate Clinical Response (ACR).


Secondary Outcome Measures:
  • Efficacy [ Designated as safety issue: No ]
    • Proportion of subjects without relapse of P. vivax at 2, 3 and 4 months.
    • Determination of Parasite, Gametocyte, and Fever Clearance Time (PCT, GCT, and FCT).

  • Safety [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of the tafenoquine dosing regimens.

  • Pharmacology [ Designated as safety issue: No ]
    Population pharmacokinetic parameters (CL/F, V/F, ka) will be estimated for tafenoquine.


Enrollment: 70
Study Start Date: September 2003
Study Completion Date: January 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 tafenoquine
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.
Drug: Tafenoquine
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.
Active Comparator: Cohort 1-Chloroquine
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.
Drug: Chloroquine + Primaquine
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.
Experimental: Cohort 2 Tafenoquine
Tafenoquine (600 mg base) and chloroquine placebo x 1d, chloroquine placebo x 2 days, followed by primaquine placebo for 14 days.
Drug: tafenoquine
Tafenoquine (600 mg base) and chloroquine placebo x 1d, chloroquine placebo x 2 days, followed by primaquine placebo for 14 days.
Active Comparator: Cohort 2 Chloroquine
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.
Drug: Chloroquine + Primaquine
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.

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01290601

Locations
Thailand
Bangkok Hospital for Tropical Diseases/Mahidol University
Bangkok, Thailand, 10400
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
GlaxoSmithKline
Investigators
Principal Investigator: Sornchai Looareesuwan, MD Mahidol University
  More Information

No publications provided

Responsible Party: Dr. Robert E. Miller, U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01290601     History of Changes
Other Study ID Numbers: TQ study 058
Study First Received: February 3, 2011
Last Updated: February 3, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
malaria
Plasmodium vivax
adults
treatment
tafenoquine

Additional relevant MeSH terms:
Malaria
Malaria, Vivax
Protozoan Infections
Parasitic Diseases
Chloroquine
Chloroquine diphosphate
Primaquine
Tafenoquine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014