Clinical trial NCT04073953: Primaquine Enantiomers in G6PD Deficient Human Volunteers
Official title: Metabolism and Pharmacokinetics of Primaquine Enantiomers in G6PD Deficient Human Volunteers Receiving a Five Day Dose Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: G6PD Deficiency
Keywords: G6PD
Hemolysis
Primaquine
Pharmacokinetics
Malaria
Lead sponsor: University of Mississippi, Oxford
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
First posted: 2019-08-29
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study is a single center, prospective, cross-over phase 1 trial. Eighteen subjects will be enrolled in the study evaluating the metabolism, pharmacokinetic behavior and tolerability of primaquine enantiomers and placebo over the course of 5 days.

Detailed description: Each subject will receive a 15 mg dose of one enantiomer (SPQ or RPQ or Placebo) daily for up to 5 days, with careful monitoring of hematological parameters before and after each dose. In addition to the general CMP14 safety criteria, any subject who displays a fractional hemoglobin drop of 15% below his/her baseline value, then drug administration will stop (e.g. for baseline Hgb of 14 g/dL, if there is at any point a decrease of 2.1 g/dL). Hematocrit will be similarly monitored, with proportional stop criteria. Elevation in total bilirubin to 2.0 mg/dL or greater will also be used as a stopping criterion. After stopping drug administration (5 days or whenever stop criteria are met), subjects will have a 3-week washout period, and the study repeated with the other enantiomer, and similarly with Placebo.

Eligibility criteria: Inclusion Criteria:

* G6PD deficient, otherwise normal healthy adults aged 18 to 65

Exclusion Criteria:

* Known history of liver, kidney or hematological disease (other than G6PD deficiency)
* Known history of cardiac disease, non-sinus rhythm arrhythmia or QT prolongation
* Autoimmune disorders
* Report of an active infection
* Subject is pregnant or breast-feeding, or is expecting to conceive during the study.

Primary outcomes:
measure: Change in Methemoglobin concentration in blood from baseline
timeFrame: Days 0, 3, 5
Secondary outcomes:
measure: Primaquine Plasma Concentration, ng/mL
timeFrame: Days 0, 3, 5
measure: Carboxy-Primaquine Plasma Contration, ng/mL
timeFrame: Days 0, 3, 5
measure: Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL
timeFrame: Days 0, 3, 5
measure: Primaquine Orthoquinone Plasma concentration, ng/mL
timeFrame: Days 0, 3, 5
measure: Change in Hematocrit (%) compared to baseline
timeFrame: Days 0, 3, 5
measure: Change in Hemoglobin (g/dL) compared to baseline
timeFrame: Days 0, 3, 5
measure: Change is AST (U/L) compared to baseline
timeFrame: Days 0, 3, 5
measure: Change in ALT (U/L) compared to baseline
timeFrame: Days 0, 3, 5
measure: Change in total Bilirubin (mg/dL) compared to baseline
timeFrame: Days 0, 3, 5
Other outcomes:
Locations:
city: University
country: United States
facility: University of Mississippi
state: Mississippi
Study officials:
affiliation: University of Mississippi Medical Center
name: Larry Walker, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: