Clinical trial NCT03934450: Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
Official title: Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Glucose 6 Phosphate Dehydrogenase Deficiency
Keywords: Hemolysis
Primaquine
Pharmacokinetics
Lead sponsor: University of Mississippi, Oxford
Sponsor class: OTHER
First posted: 2019-05-01
Enrollment: 36
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
Intervention model description: This study is a single center, prospective, cross-over phase 1 trial. Thirty-six participants will be enrolled into a two Cohort pharmacokinetic study evaluating the metabolism, pharmacokinetic behavior and tolerability of two dose levels (low/high) of primaquine enantiomers (and placebo) over the course of 7 days.

Placebo will be added in order to assess tolerability of enantiomers. Placebo control is needed in non-drug related clinical responses.
Primary purpose: BASIC_SCIENCE

Brief summary: To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers, receiving study drug over the course of 7 days.

Detailed description: The primary objective of this project is to investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers. Based on the results of this study, if one enantiomer seems to show a better safety profile (in terms of hematological effects), an analogous study will be carried out in G6PD deficient individuals (under a separate protocol). The studies are primarily aimed at understanding the tolerability and safety of the enantiomers in G6PD deficiency. If one shows a better safety profile, ultimately the evaluation of its efficacy will be required.

Eligibility criteria: Inclusion Criteria:

* Normal, healthy adults aged 18 to 65 years

Exclusion Criteria:

* Known history of liver, kidney or hematological disease
* Known history of cardiac disease, Non Sinus Rhythm arrhythmia or QT prolongation
* Autoimmune disorders
* Report of an active infection
* Evidence of G6PD deficiency
* Participant 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, 7
Secondary outcomes:
measure: Primaquine Plasma concentration, ng/mL
timeFrame: Days 0, 3, 5, 7
measure: Carboxy- Primaquine Plasma concentration, ng/mL
timeFrame: Days 0, 3, 5, 7
measure: Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL
timeFrame: Days 0, 3, 5, 7
measure: Primaquine Orthoquinone Plasma concentration, ng/mL
timeFrame: Days 0, 3, 5, 7
measure: Change in Hematocrit (%) Compared to baseline
timeFrame: Days 0, 3, 5, 7
measure: Change in Hemoglobin (g/dL) Compared to baseline
timeFrame: Days 0, 3, 5, 7
measure: Change in AST (U/L) Compared to baseline
timeFrame: Days 0, 3, 5, 7
measure: Change in ALT (U/L) Compared to baseline
timeFrame: Days 0, 3, 5, 7
measure: Change in Total Bilirubin (mg/dL) Compared to baseline
timeFrame: Days 0, 3, 5, 7
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, Phd
role: PRINCIPAL_INVESTIGATOR
References: