Primaquine Enantiomers in G6PD Deficient Human Volunteers

Overview

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.

Full Title of Study: “Metabolism and Pharmacokinetics of Primaquine Enantiomers in G6PD Deficient Human Volunteers Receiving a Five Day Dose Regimen”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 1, 2021

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.

Interventions

  • Drug: RPQ
    • The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
  • Drug: SPQ
    • The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
  • Drug: Placebo
    • The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.

Arms, Groups and Cohorts

  • Experimental: RPQ (-) enantiomer
    • Cohort 1 will receive 15mg of RPQ every day for 5 days. Cohort 2 will receive 22.5 mg of RPQ every day for five days.
  • Experimental: SPQ (+) enantiomer
    • Cohort 1 will receive 15mg of SPQ every day for 5 days. Cohort 2 will receive 22.5 mg of SPQ every day for five days.
  • Placebo Comparator: Placebo
    • Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days.

Clinical Trial Outcome Measures

Primary Measures

  • Change in Methemoglobin concentration in blood from baseline
    • Time Frame: Days 0, 3, 5
    • Change in Methemoglobin concentration in blood from baseline (% hemoglobin)

Secondary Measures

  • Primaquine Plasma Concentration, ng/mL
    • Time Frame: Days 0, 3, 5
    • Plasma concentrations of parent drug
  • Carboxy-Primaquine Plasma Contration, ng/mL
    • Time Frame: Days 0, 3, 5
    • Plasma concentrations of carboxy-primaquine metabolite
  • Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL
    • Time Frame: Days 0, 3, 5
    • Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
  • Primaquine Orthoquinone Plasma concentration, ng/mL
    • Time Frame: Days 0, 3, 5
    • Plasma concentrations of Primaquine Orthoquinone metabolite
  • Change in Hematocrit (%) compared to baseline
    • Time Frame: Days 0, 3, 5
    • Change in Hematocrit (%) compared to baseline
  • Change in Hemoglobin (g/dL) compared to baseline
    • Time Frame: Days 0, 3, 5
    • Change in Hemoglobin (g/dL) compared to baseline
  • Change is AST (U/L) compared to baseline
    • Time Frame: Days 0, 3, 5
    • Change is AST (U/L) compared to baseline; used to monitor liver function
  • Change in ALT (U/L) compared to baseline
    • Time Frame: Days 0, 3, 5
    • Change in ALT (U/L) compared to baseline; used to monitor liver function
  • Change in total Bilirubin (mg/dL) compared to baseline
    • Time Frame: Days 0, 3, 5
    • Change in total Bilirubin (mg/dL) compared to baseline; used to monitor liver function and red cell integrity

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Mississippi, Oxford
  • Collaborator
    • University of Colorado, Denver
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Larry Walker, Ph.D., Principal Investigator, University of Mississippi Medical Center
  • Overall Contact(s)
    • Larry Walker, Ph.D., 662-915-1005, lwalker@olemiss.edu

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.