Determining a Tolerable Dose of Primaquine in G6PD-deficient Persons Without Malaria in Mali

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02535767
• Date of registration: 07/08/2015
• Prospective Registration: No
• Primary sponsor: University of California, San Francisco
• Public title: Determining a Tolerable Dose of Primaquine in G6PD-deficient Persons Without Malaria in Mali PQSAFETY
• Scientific title: Determining a Tolerable Dose of Primaquine in G6PD-deficient Persons Without Malaria in Mali
• Date of first enrolment: August 2015
• Target sample size: 28
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02535767
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Mali

Contacts

• Name: Roland Gosling, PhD, MS
• Affiliation: University of California, San Francisco

Key inclusion & exclusion criteria

Inclusion Criteria:

- Males ages 18- 50 (inclusive)

- Ability to swallow oral medication

- Informed consent

- Willing and able to participate in the study for 28 days

For the G6PDd participants:

- G6PDd defined by Carestart 3 rapid diagnostic test or

- The OSMMR2000 G6PD qualitative test

For the G6PDn participants:

- G6PDn defined by Carestart 3 rapid diagnostic test or

- The OSMMR2000 G6PD qualitative test

Exclusion Criteria:

- Moderate to severe anemia (Hb < 10 g/dL)

- Malaria infection by blood smear

- Individuals with known positive HIV test

- Individuals with known positive hepatitis B test.

- Known allergy to study drugs

- Current use of medication (for tuberculosis, HIV, or any drugs that have hemolytic
potential in G6PDd individuals including sulphonamides, dapsone, nitrofurantoin,
nalidixic acid, ciprofloxacin, methylene blue, toluidine blue, phenazopyridine, and
co-trimoxazole)

- The individual is unwilling to abstain from the ingestion of grapefruit-containing
products from 72 hours prior to the start of dosing until the study is complete

- Use of antimalarials within 2 weeks before contact with the study team as reported by
the patient

- History of blood transfusion or a bleed of > 500 mLs within the last 3 months, as
reported by the patient

- Reported history of high alcohol intake (> 14 units per week, each unit is equivalent
to 10 g of alcohol (1 glass of wine or 1 bottle of beer or one shot of distilled
spirits), within 6 months of study as reported by the patient

- Reported use of illicit drugs (marijuana, heroin, cocaine, methamphetamine) or
dependence within 6 months of study, as reported by the patient

- Participants who vomit within 1 hour after administration of primaquine (will be
removed from the analysis and will not count towards the total sample size, though
they will be followed as any other enrolled individual)

- Already enrolled in this study.



Age minimum: 18 Years
Age maximum: 50 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Malaria

Intervention(s)

Drug: Primaquine

Primary Outcome(s)

Primary outcome: the change in hemoglobin concentration from baseline levels following a single low-dose of primaquine not to exceed 0.75 mg/kg. [Time Frame: Between day 0 and day 10.]

Secondary Outcome(s)

To measure the occurrence of reticulocytosis (by microscopic quantification of reticulocytes stained with brilliant cresyl blue / 1,000 RBCs) on each day of followup, at each primaquine dose, among G6PD deficient men, in comparison with G6PD normal men [Time Frame: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, and 28]

To measure the occurrence of absolute and fractional change in hemoglobin concentration (g/dL) on day 7 vs. baseline at each primaquine dose among G6PD deficient men, in comparison with G6PD normal men [Time Frame: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, and 28]

Area Under Curve (AUC) for carboxyprimaquine [Time Frame: Hours 1, 2, 4, 6, 8, and 24 after primaquine administration]

Area Under Curve (AUC) for select minor metabolites of primaquine [Time Frame: Hours 1, 2, 4, 6, 8, and 24 after primaquine administration]

Area Under Curve (AUC) for primaquine [Time Frame: Hours 1, 2, 4, 6, 8, and 24 after primaquine administration]

Maximal concentration (Cmax) for primaquine [Time Frame: Hours 1, 2, 4, 6, 8, and 24 after primaquine administration]

To monitor methemoglobin levels (%) on each day of followup, at each primaquine dose among G6PD deficient men, in comparison with G6PD normal men [Time Frame: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, and 28]

Maximal concentration (Cmax) for carboxyprimaquine [Time Frame: Hours 1, 2, 4, 6, 8, and 24 after primaquine administration]

Maximal concentration (Cmax) for select minor metabolites of primaquine [Time Frame: Hours 1, 2, 4, 6, 8, and 24 after primaquine administration]

To determine G6PD enzyme activity (semiquantitative testing, U/g Hb) [Time Frame: Day 0]

Cytochrome P450 (CYP) 2D6 genotyping [Time Frame: Day 0]

To measure the occurrence of adverse events, graded by severity, at each primaquine dose among G6PD deficient men [Time Frame: Days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, and 28]

Secondary ID(s)

14-14495

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bill and Melinda Gates Foundation

Malaria Research and Training Center, Bamako, Mali

University of Mississippi Medical Center

Radboud University