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

NCT01290601 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: TQ study 058A-12055
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria; Plasmodium Vivax

Keywords

malaria; Plasmodium vivax; adults; treatment; tafenoquine

Outcome Measures

Primary Outcomes (1)

• Adequate Clinical Response (ACR) of Tafenoquine: 28 Day Cure Rate

  A subject will be considered a success (cure) if they have an Adequate Clinical Response (ACR). Tafenoquine was efficacious if the lower bound of the two-sided 90% confidence interval for the day 28 cure rate was not less than 85%

  28 Days

Secondary Outcomes (3)

• Number of Subjects Without Relapse of P. Vivax

  Day 28, Months 2, 3 and 4

• Safety and Tolerability of Tafenoquine as Defined by Most Common Adverse Events (AEs)

  90 Days

• Parasite and Gametocyte Clearance Time (PCT and GCT)

  up to day 7 after baseline smear

Other Outcomes (1)

• Fever Clearance Time (FCT)

  through day 7

Study Arms (4)

Cohort 1 Tafenoquine

EXPERIMENTAL

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

Cohort 1-Chloroquine

ACTIVE COMPARATOR

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

Cohort 2 Tafenoquine

EXPERIMENTAL

Tafenoquine (600 mg base) and chloroquine placebo x 1d, chloroquine placebo x 2 days, followed by primaquine placebo for 14 days.

Drug: tafenoquine

Cohort 2 Chloroquine

ACTIVE COMPARATOR

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

Interventions

tafenoquine DRUG

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.

Cohort 1 Tafenoquine

Chloroquine + Primaquine DRUG

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.

Cohort 1-Chloroquine

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Positive smear for P. vivax.
• Parasite density \> 500 and \< 200,000/μl
• Age: 20-60 years old
• Willing to sign consent form
• Willing to be hospitalized for 29 days and remain in a malaria free region for 60 days thereafter for follow-up.
• 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.

You may not qualify if:

• Mixed malaria infections by Field's stain.
• 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.
• Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
• Demonstrated glucose-6-phosphate dehydrogenase deficiency.
• Subject has taken other anti-malarials (mefloquine, primaquine, chloroquine) within the past 30 days by history
• 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).
• History of allergy to chloroquine, mefloquine, tafenoquine, primaquine or any other 8-aminoquinolines.
• Subject has taken another investigational drug within 30 days or 5 half lives (whichever is longer), of study start.
• History of previous eye surgery or have evidence of corneal or retinal abnormalities identified in baseline ophthalmological examination.
• 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).
• Subjects whom, after examination by the study ophthalmologist, are judged to be at risk for acute angle closure glaucoma.
• Females who are pre-menarchal.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Bangkok Hospital for Tropical Diseases/Mahidol University

Bangkok, 10400, Thailand

Location

Related Publications (2)

• Warrasak S, Euswas A, Fukuda MM, Ittiverakul M, Miller RS, Krudsood S, Ohrt C. Comparative ophthalmic assessment of patients receiving tafenoquine or chloroquine/primaquine in a randomized clinical trial for Plasmodium vivax malaria radical cure. Int Ophthalmol. 2019 Aug;39(8):1767-1782. doi: 10.1007/s10792-018-1003-2. Epub 2018 Sep 29.

  PMID: 30269312 DERIVED

• Fukuda MM, Krudsood S, Mohamed K, Green JA, Warrasak S, Noedl H, Euswas A, Ittiverakul M, Buathong N, Sriwichai S, Miller RS, Ohrt C. A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria. PLoS One. 2017 Nov 9;12(11):e0187376. doi: 10.1371/journal.pone.0187376. eCollection 2017.

  PMID: 29121061 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Vivax

Interventions

tafenoquine; Chloroquine; Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

IDMC determined that Cohort 1 failed to meet specified endpoint for d28 cure rate; Cohort 2 wasn't initiated and follow-up in Cohort 1 should be completed according to protocol. Following last subjects last visit for Cohort 1 study was terminated.

Results Point of Contact

• Title: Shirley Lee-Lecher
• Organization: WRAIR

usarmy.detrick.medcom-wrair.mbx.ocid@mail.mil

301-251-5000

Study Officials

• Sornchai Looaree Suwan, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Only if Cohort 1 met specified endpoint criteria would Cohort 2 begin enrollment

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: February 7, 2011
• Study Start: September 15, 2003
• Primary Completion: January 10, 2005
• Study Completion: January 10, 2005
• Last Updated: February 23, 2018
• Results First Posted: January 25, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)