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An Evaluation of Weekly Tafenoquine

Primary Purpose

Falciparum Parasitaemia

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Tafenoquine

Mefloquine

Placebo

About this trial

This is an interventional treatment trial for Falciparum Parasitaemia focused on measuring Falciparum Parasitaemia, Malaria

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male or female volunteers who provided informed consent (a healthy volunteer was defined as one who was free of ailments that might cause difficulty in evaluating drug efficacy or adverse experiences).
Subjects aged 18-55 years.
Subjects planning to reside in the study area for the entire study duration of approximately 70 weeks

Exclusion Criteria:

Subjects with positive parasitaemia following halofantrine treatment for radical cure.
Subjects with any medical condition which, in the opinion of the investigator, made the subject unsuitable to enter the study.
Subjects with personal or family history of seizures.
Female subjects with a positive serum beta-HCG5 (tested during screening and within 48 hours of first drug administration and approximately monthly thereafter).
Women who were pregnant or lactating or who in the opinion of the investigator were at risk of becoming pregnant.
Subjects with clinically significant abnormalities (to include but not limited to abnormal hepatic or renal function) as determined by history, physical and routine blood chemistries and haematology values. Subjects who had demonstrated hypersensitivity to any of the study drugs especially to any other 8-aminoquinolines.
Subjects unwilling to report for drug administration or blood drawing during the 70 week duration of the study.
Subjects with G6PD deficiency.
Subjects with laboratory guideline values for exclusion: haemoglobin <10 gm/dL, platelets <80,000/mm3, WBC <3000ul3, creatinine or ALT more than twice the upper limit of normal for age.
Subjects with an abnormal ECG, particularly an extended QTc interval > 0.42 seconds.
Subjects taking any other anti-malarial product, or who had taken an antimalarial drug other than halofantrine within the previous two weeks.
Subjects who had received an investigational drug (a new chemical entity not registered for use) within 30 days or 5 half-lives whichever was the longer.
Subjects with a history of psychiatric disorder.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Tafenoquine

Mefloquine

Placebo

Arm Description

Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks.

Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks.

Placebo

Outcomes

Primary Outcome Measures

Prophylactic Outcome Defined by the Subject Having no Positive Smears

Prophylactic outcome (success/failure) at the end of the prophylactic treatment phase; outcome was based on absence/presence of asexual stage parasites of any Plasmodium species on a single blood smear.

Secondary Outcome Measures

Protective Efficacy Based on Two Consecutive Positive Smears

Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. Analysis was based on a calculation of protective efficacy (PE) of tefaenoquine, defined as (1-relative risk of developing parasitaemia tafenoquine: placebo) x100% and 95.5% confidence intervals were constructed for the relative risk using Koopman's method.

Time to a Single Positive Smear

Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. 95.5% confidence intervals were constructed for the relative risk.

Full Information

NCT ID

NCT02488980

First Posted

June 24, 2015

Last Updated

April 26, 2017

Sponsor

U.S. Army Medical Research and Development Command

Collaborators

SmithKline Beecham

1. Study Identification

Unique Protocol Identification Number

NCT02488980

Brief Title

An Evaluation of Weekly Tafenoquine

Official Title

A Randomized, Double Blind, Placebo Controlled Evaluation of Weekly Tafenoquine (WR 238605/SB252263) Compared to Mefloquine for Chemosuppression of Plasmodium Falciparum in Western Kenya

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

May 2000 (undefined)

Primary Completion Date

October 2000 (Actual)

Study Completion Date

March 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

U.S. Army Medical Research and Development Command

Collaborators

SmithKline Beecham

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This was a placebo controlled, randomised, double-blind, double-dummy study of the efficacy of weekly tafenoquine compared with weekly mefloquine or placebo in the chemosuppression of P. falciparum in Nyanza Province, western Kenya.

Detailed Description

Subjects were treated for 3 days with halofantrine to clear any existing parasitaemia. At the end of the clearance period, subjects free from malaria parasitaemia were randomized and received a loading dose of the study treatment (tafenoquine 200 mg, Mefloquine 250 mg or placebo) for tree days, followed by study treatment (tafenoquine 200 mg, mefloquine 250 mg or placebo, respectively) once a week for 24 weeks. After the treatment period subjects attended weekly follow-up safety visits until week 28.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Falciparum Parasitaemia

Keywords

Falciparum Parasitaemia, Malaria

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

306 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tafenoquine

Arm Type

Experimental

Arm Description

Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks.

Arm Title

Mefloquine

Arm Type

Active Comparator

Arm Description

Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Tafenoquine

Intervention Description

Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.

Intervention Type

Drug

Intervention Name(s)

Mefloquine

Intervention Description

Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo for three days followed by placebo once a week for 24 weeks

Primary Outcome Measure Information:

Title

Prophylactic Outcome Defined by the Subject Having no Positive Smears

Description

Time Frame

24 Weeks

Secondary Outcome Measure Information:

Title

Protective Efficacy Based on Two Consecutive Positive Smears

Description

Time Frame

24 Weeks

Title

Time to a Single Positive Smear

Description

Time Frame

24 Weeks

Other Pre-specified Outcome Measures:

Title

Safety (SAEs and AEs)

Description

The most commonly reported experiences in subject occurring in at least 20% of subjects in any treatment group.

Time Frame

28 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male or female volunteers who provided informed consent (a healthy volunteer was defined as one who was free of ailments that might cause difficulty in evaluating drug efficacy or adverse experiences). Subjects aged 18-55 years. Subjects planning to reside in the study area for the entire study duration of approximately 70 weeks Exclusion Criteria: Subjects with positive parasitaemia following halofantrine treatment for radical cure. Subjects with any medical condition which, in the opinion of the investigator, made the subject unsuitable to enter the study. Subjects with personal or family history of seizures. Female subjects with a positive serum beta-HCG5 (tested during screening and within 48 hours of first drug administration and approximately monthly thereafter). Women who were pregnant or lactating or who in the opinion of the investigator were at risk of becoming pregnant. Subjects with clinically significant abnormalities (to include but not limited to abnormal hepatic or renal function) as determined by history, physical and routine blood chemistries and haematology values. Subjects who had demonstrated hypersensitivity to any of the study drugs especially to any other 8-aminoquinolines. Subjects unwilling to report for drug administration or blood drawing during the 70 week duration of the study. Subjects with G6PD deficiency. Subjects with laboratory guideline values for exclusion: haemoglobin <10 gm/dL, platelets <80,000/mm3, WBC <3000ul3, creatinine or ALT more than twice the upper limit of normal for age. Subjects with an abnormal ECG, particularly an extended QTc interval > 0.42 seconds. Subjects taking any other anti-malarial product, or who had taken an antimalarial drug other than halofantrine within the previous two weeks. Subjects who had received an investigational drug (a new chemical entity not registered for use) within 30 days or 5 half-lives whichever was the longer. Subjects with a history of psychiatric disorder.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jose Stoute, MD

Organizational Affiliation

Penn State Hershey Infectious Diseases

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

SmithKline Beecham

Citations:

PubMed Identifier

28495354

Citation

Novitt-Moreno A, Ransom J, Dow G, Smith B, Read LT, Toovey S. Tafenoquine for malaria prophylaxis in adults: An integrated safety analysis. Travel Med Infect Dis. 2017 May-Jun;17:19-27. doi: 10.1016/j.tmaid.2017.05.008. Epub 2017 May 8.

Results Reference

derived

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An Evaluation of Weekly Tafenoquine

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