Escalating Monthly Doses of Tafenoquine in Healthy Volunteers — TQ  

Prophylaxis Clinical Trial

Official title: Safety, Tolerability and Pharmacokinetics of Tafenoquine After Weekly and Escalating Monthly Doses of Tafenoquine in Healthy Vietnamese Volunteers

Status Not yet recruiting

Clinical Trial 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).

Clinical Trial Description

This is an open-label study to evaluate the safety, tolerability and PK of tafenoquine after weekly and two monthly doses of tafenoquine in healthy participants. 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.

The 200 healthy participants will be divided into two cohorts (A and B) of 100 participants to fully cover the three tafenoquine regimens (i.e. weekly, low monthly and high monthly) in obtaining study information (e.g. AEs) and biospecimens for monitoring the safety, tolerability and PK of tafenoquine.

Tafenoquine: Arakoda™ tablets (each containing 100 mg of tafenoquine base) are dark pink, capsule shaped, debossed with "TQ100" on one side and plain on the other. Arakoda™ tablets are supplied in blister packs. Each blister pack contains 8 tablets. Monthly tafenoquine will be administered as 100 mg oral tafenoquine tablets (Arakoda™) identical to those marketed for weekly prophylaxis.

Objectives: Primary Objective: In a dose escalating study in the same healthy participants compare the frequency of treatment-related safety and adverse events (AEs) after weekly 200 mg tafenoquine and two monthly (600 mg and 800 mg) tafenoquine regimens.

Secondary Objectives:

• Characterize the PK profiles of tafenoquine after weekly 200 mg and two monthly (600 mg and 800 mg) tafenoquine regimens in the same healthy participants.

• Characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship between blood tafenoquine concentrations and safety and tolerability of the weekly 200 mg and two monthly (600 mg or 800 mg) tafenoquine regimens in the same healthy participants.

• Determine the association of tafenoquine and its metabolite 5,6, orthoquinone in red blood cells, the site of action of the drug's blood schizontocidal activity.

• Determine the ex vivo antimalarial activity of tafenoquine in participants' plasma samples after tafenoquine administration (weekly and monthly regimens) against Plasmodium falciparum strains with different levels of drug susceptibility.

Study Population: Two hundred healthy participants are planned to be enrolled in this study for Parts 1 to 3. It is planned to recruit 200 participants from 108 Military Central Hospital.

The healthy participants will be judged to be in good health based on medical history, physical examination, blood chemistries, urinalysis, serology, normal electrocardiogram (ECG), glucose-6-phosphate dehydrogenase (G6PD) normal, and free of infectious diseases, psychiatric concerns, allergies and other medical conditions that the Investigator deems may compromise the potential participant's safety and wellbeing. ;

Related Conditions & MeSH terms

• Prophylaxis

• NCT number: NCT05203744
• Study type: Interventional
• Source: Naval Medical Research Center
• Contact: John S Brooks, MD MPH
• Phone: +84 243935 2166
• Email: brooksjs@state.gov
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 10, 2022
• Completion date: December 3, 2022