Escalating Monthly Doses of Tafenoquine in Healthy Volunteers

Summary

In 2018, the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) approved tafenoquine for malaria prevention. The approved tafenoquine prophylactic regimen is 600 mg loading dose (200 mg daily for 3 days) prior to travel and a weekly 200 mg maintenance dose commencing 7 days after the last loading dose. This weekly tafenoquine regimen is more convenient with potentially improved compliance than daily doxycycline or atovaquone proguanil (Malarone), the other recommended prophylactic agents by the U.S. Centers for Disease Control and Prevention (CDC) for the prevention of malaria infections.

Current assumptions are that a systemic minimum inhibitory concentration (MIC) of tafenoquine in plasma is 80 ng/mL in nonimmune individuals is required to prevent symptomatic breakthroughs of malaria infections. Because of tafenoquine's lengthy blood elimination half-life of 2-3 weeks, a monthly regimen of 600 mg and 800 mg of tafenoquine in individuals weighing 60 kg and 80 kg, respectively, have pharmacokinetic (PK) profiles (i.e., drug concentration versus time curves) of achieving MIC values of at least 80 ng/mL in the majority of healthy individuals. The aim of this study is to determine whether the safety and tolerability profiles in healthy participants taking monthly doses of 600 mg or 800 mg tafenoquine are comparable in the same participants taking weekly 200 mg tafenoquine.

Study Hypothesis: The study hypothesis is that the frequency of tafenoquine-related safety (e.g. blood chemistries) and adverse events (AEs) in healthy participants who take a higher dose (600 mg and 800 mg) of tafenoquine monthly would be comparable to the frequency of treatment related safety and AEs in the same individuals who take weekly tafenoquine (200 mg).

Conditions

• Prophylaxis

Interventions

DRUG

Tafenoquine prophylaxis

The study will be conducted in three parts with 200 participants invited to participate in the study. * Part 1 consist of 200 participants to be administered a loading dose of 600 mg tafenoquine (200 mg daily for 3 days) followed by 200 mg weekly for two weeks. * Part 2: The same participants from Part 1 will be administered a monthly dose of tafenoquine (600 mg total, given as 300 mg split over 2 days) for two consecutive months. This monthly dose of 600 mg tafenoquine is designated the "low" monthly tafenoquine dose. * Part 3: The same participants from Parts 1 and 2 will be administered a monthly dose of tafenoquine (800 mg total, given as 400 mg split over 2 days) for two consecutive months. This monthly dose of 800 mg tafenoquine is designated the high monthly tafenoquine dose.

Sponsors & Collaborators

• Naval Medical Research Unit TWO (NAMRU-2)

  collaborator UNKNOWN

• Australian Defence Force Malaria and Infectious Disease Institute (ADF MIDI)

  collaborator UNKNOWN

• The 108 Military Central Hospital

  collaborator OTHER_GOV

• Naval Environmental Preventive Medicine Unit TWO (NEPMU-2)

  collaborator UNKNOWN

• Naval Medical Research Center

  lead FED

Principal Investigators

• Michael D Edstein, PhD · Australian Defence Force Malaria and Infectious Disease Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-05-10

Primary Completion

2022-12-03

Completion

2022-12-03

FDA Drug

Yes

Countries

• Vietnam

Study Locations