Primaquine Enantiomers in G6PD Deficient Human Volunteers

NCT04073953 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PQ Study 3
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

G6PD Deficiency

Keywords

G6PD; Hemolysis; Primaquine; Pharmacokinetics; Malaria

Outcome Measures

Primary Outcomes (1)

• Change in Methemoglobin concentration in blood from baseline

  Change in Methemoglobin concentration in blood from baseline (% hemoglobin)

  Days 0, 3, 5

Secondary Outcomes (9)

• Primaquine Plasma Concentration, ng/mL

  Days 0, 3, 5

• Carboxy-Primaquine Plasma Contration, ng/mL

  Days 0, 3, 5

• Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL

  Days 0, 3, 5

• Primaquine Orthoquinone Plasma concentration, ng/mL

  Days 0, 3, 5

• Change in Hematocrit (%) compared to baseline

  Days 0, 3, 5

Study Arms (3)

RPQ (-) enantiomer

EXPERIMENTAL

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.

Drug: RPQ

SPQ (+) enantiomer

EXPERIMENTAL

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.

Drug: SPQ

Placebo

PLACEBO COMPARATOR

Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days.

Drug: Placebo

Interventions

RPQ DRUG

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

Also known as: R-(-) Enantiomer of Primiquine Phosphate

RPQ (-) enantiomer

SPQ DRUG

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

Also known as: S-(+) Enantiomer of Primaquine Phosphate

SPQ (+) enantiomer

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Mississippi, Oxford: lead
• University of Colorado, Denver: collaborator

Study Sites (1)

University of Mississippi

University, Mississippi, 38677, United States

Location

MeSH Terms

Conditions

Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Malaria

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Larry Walker, Ph.D.

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: August 29, 2019
• Study Start: September 1, 2020
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)