Primaquine Enantiomers in G6PD Deficient Human Volunteers

G6PD Deficiency Clinical Trial

Official title:

Metabolism and Pharmacokinetics of Primaquine Enantiomers in G6PD Deficient Human Volunteers Receiving a Five Day Dose Regimen

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04073953
• Other study ID #: PQ Study 3
• Status: Recruiting
• Phase: Phase 1
• Start date: September 1, 2020
• Est. completion date: September 1, 2022

Study information

• Verified date: October 2020
• Source: University of Mississippi, Oxford
• Contact: Larry Walker, Ph.D.
• Phone: 662-915-1005
• Email: lwalker[@]olemiss.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• G6PD Deficiency
• Glucosephosphate Dehydrogenase Deficiency

Intervention

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

Locations

Country	Name	City	State
United States	University of Mississippi	University	Mississippi

Sponsors (3)

Lead Sponsor	Collaborator
University of Mississippi, Oxford	Southern Research Institute, University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Methemoglobin concentration in blood from baseline	Change in Methemoglobin concentration in blood from baseline (% hemoglobin)	Days 0, 3, 5
Secondary	Primaquine Plasma Concentration, ng/mL	Plasma concentrations of parent drug	Days 0, 3, 5
Secondary	Carboxy-Primaquine Plasma Contration, ng/mL	Plasma concentrations of carboxy-primaquine metabolite	Days 0, 3, 5
Secondary	Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL	Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite	Days 0, 3, 5
Secondary	Primaquine Orthoquinone Plasma concentration, ng/mL	Plasma concentrations of Primaquine Orthoquinone metabolite	Days 0, 3, 5
Secondary	Change in Hematocrit (%) compared to baseline	Change in Hematocrit (%) compared to baseline	Days 0, 3, 5
Secondary	Change in Hemoglobin (g/dL) compared to baseline	Change in Hemoglobin (g/dL) compared to baseline	Days 0, 3, 5
Secondary	Change is AST (U/L) compared to baseline	Change is AST (U/L) compared to baseline; used to monitor liver function	Days 0, 3, 5
Secondary	Change in ALT (U/L) compared to baseline	Change in ALT (U/L) compared to baseline; used to monitor liver function	Days 0, 3, 5
Secondary	Change in total Bilirubin (mg/dL) compared to baseline	Change in total Bilirubin (mg/dL) compared to baseline; used to monitor liver function and red cell integrity	Days 0, 3, 5