Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen

NCT03934450 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PQ Study 2
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria; Glucose 6 Phosphate Dehydrogenase Deficiency

Keywords

Hemolysis; Primaquine; Pharmacokinetics

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, 7

Secondary Outcomes (9)

• Primaquine Plasma concentration, ng/mL

  Days 0, 3, 5, 7

• Carboxy- Primaquine Plasma concentration, ng/mL

  Days 0, 3, 5, 7

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

  Days 0, 3, 5, 7

• Primaquine Orthoquinone Plasma concentration, ng/mL

  Days 0, 3, 5, 7

• Change in Hematocrit (%) Compared to baseline

  Days 0, 3, 5, 7

Study Arms (4)

RPQ (-) enantiomer

EXPERIMENTAL

Cohort 1 will receive 15 mg of RPQ (3A) every day for 7 days Cohort 2 will receive 22.5 mg of RPQ (3A) every day for 7 days

Drug: RPQ

SPQ (+) enantiomer

EXPERIMENTAL

Cohort 1 will receive 15 mg of SPQ (2A) every day for 7 days Cohort 2 will receive 22.5 mg of SPQ (2A) every day for 7 days

Drug: SPQ

Primaquine Phosphate

ACTIVE COMPARATOR

Cohort 1 will receive 30 mg of RSPQ (1A) every day for 7 days Cohort 2 will receive 45 mg of RSPQ (1A) every day for 7 days

Drug: Primaquine Phosphate

Placebo

PLACEBO COMPARATOR

Cohort 1 will receive placebo (4A) capsules everyday for seven days Cohort 2 will receive placebo (4A) capsules everyday for seven days

Drug: Placebo

Interventions

RPQ DRUG

The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.

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

RPQ (-) enantiomer

SPQ DRUG

The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.

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

SPQ (+) enantiomer

Primaquine Phosphate DRUG

The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.

Also known as: Racemic Primaquine

Primaquine Phosphate

Placebo DRUG

The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.

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:

• Normal, healthy adults aged 18 to 65 years

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Mississippi, Oxford: lead

Study Sites (1)

University of Mississippi

University, Mississippi, 38677, United States

Location

MeSH Terms

Conditions

Malaria; Glucosephosphate Dehydrogenase Deficiency; Hemolysis

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; 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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Larry Walker, Phd

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will not be able to know the sequence of the drug adminstration
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: May 1, 2019
• Study Start: August 17, 2018
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: May 14, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)