Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers, Study 1

May 14, 2018 updated by: University of Mississippi, Oxford

Development of Safer Drugs for Malaria in U.S. Troops, Civilian Personnel, and Travelers: Clinical Evaluation of Primaquine Enantiomer

To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers. The specific aim is the comparative evaluation of the metabolism, pharmacokinetic behavior, and tolerability of the isomers of PQ (RPQ and SPQ and the racemic mixture RSPQ) in normal healthy human volunteers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

The overall approach is as follows: in 36 healthy volunteers with documented normal G6PD activity, we will administer a single oral dose of RPQ, SPQ, or RSPQ. At various times after dosing, we will draw blood samples, in which we will record the plasma levels of the parent drugs, along with plasma and urinary metabolites. The comparative pharmacokinetics, tolerability and hematological effects of these two enantiomers and the racemate will be assessed.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Mississippi
      • Oxford, Mississippi, United States, 38677
        • University of Mississippi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults (18-60 years of age)
  • Informed consent
  • Healthy

Exclusion Criteria:

  • Known history of liver, kidney or hematological disease;
  • known history of cardiac disease, arrhythmia, QT prolongation;
  • Autoimmune disorder;
  • Report of an active infection;
  • Evidence of G6PD deficiency

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 ( Primaquine Low Dose)

Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers.

Cohort 1 (Low Dose Level)- single dose of 15 mg of S-Primaquine and 15 mg of R-Primaquine compared to 30 mg RS-Primaquine over 24 hours. Participants will cross-over after a one week wash-out period.
Drug: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine

Cohort 1: Eighteen individuals (6 per group) Cohort 2: Eighteen individuals (6 per group)

Group 1-15 mg of S-Primaquine followed by one-week washout, 15 mg of R-Primaquine followed by one week washout, and 30 mg of RS-Primaquine.

Group 2- 15 mg of R-Primaquine followed by one-week washout, 30 mg of RSPQ followed by one week washout, and 15 mg of SPQ.

Group 3- 30 mg of RS-Primaquine followed by one week washout,15 mg of SPQ followed by a one week washout, and 15 mg of RPQ.

Other Names:
  • Primaquine
Experimental: Cohort 2 (Primaquine High Dose)

Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers.

Cohort 2 (High Dose Level)-single dose of 22.5 mg of S-Primaquine and 22.5 mg of R-Primaquine compared to 45 mg RS-Primaquine over 24 hours. Participants will cross-over among the treatment arms following a one week wash-out period between each.
Drug: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine

Cohort 1: Eighteen individuals (6 per group) Cohort 2: Eighteen individuals (6 per group)

Group 1-15 mg of S-Primaquine followed by one-week washout, 15 mg of R-Primaquine followed by one week washout, and 30 mg of RS-Primaquine.

Group 2- 15 mg of R-Primaquine followed by one-week washout, 30 mg of RSPQ followed by one week washout, and 15 mg of SPQ.

Group 3- 30 mg of RS-Primaquine followed by one week washout,15 mg of SPQ followed by a one week washout, and 15 mg of RPQ.

Other Names:
  • Primaquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg
Time Frame: between 0-24 Hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
between 0-24 Hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under Curve (AUC) for primaquine up to 24 hours after the primaquine administration
Time Frame: between 0-24 hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
between 0-24 hours
Maximum concentration (Cmax) for primaquine up to 24 hours after the primaquine administration
Time Frame: between 0-24 hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
between 0-24 hours
Area Under Curve (AUC) for carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
Time Frame: between 0-24 hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
between 0-24 hours
Maximum concentration of carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
Time Frame: between 0-24 hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
between 0-24 hours
Maximum concentration of selected metabolites primaquine (other than carboxyprimaquine) up to 24 hours after primaquine administration
Time Frame: between 0-24 hours
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers. The exact nature of these metabolites will be determined from previous animal and human studies
between 0-24 hours
hemoglobin and methemoglobin levels in the blood after administration of primaquine
Time Frame: 0-72 hours
To monitor hemoglobin and methemoglobin levels in normal human volunteers treated with single dose of primaquine not to exceed 45 mg
0-72 hours
Genotyping of Cytochrome P-450 (CYP)
Time Frame: day 0
To determine correlation between metabolism of primaquine and CYP 2D6 genotype
day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Mississippi, Oxford

Investigators

  • Principal Investigator: Babu L Tekwani, Ph.D, University of Mississippi Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2017

Primary Completion (Actual)

March 1, 2018

Study Completion (Actual)

March 1, 2018

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

September 7, 2016

First Posted (Estimate)

September 13, 2016

Study Record Updates

Last Update Posted (Actual)

May 15, 2018

Last Update Submitted That Met QC Criteria

May 14, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PQ Study 1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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