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Primaquine Enantiomers in G6PD Deficient Human Volunteers

Primary Purpose

G6PD Deficiency

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RPQ
SPQ
Placebo
Sponsored by
University of Mississippi, Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for G6PD Deficiency focused on measuring G6PD, Hemolysis, Primaquine, Pharmacokinetics, Malaria

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of MississippiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

RPQ (-) enantiomer

SPQ (+) enantiomer

Placebo

Arm Description

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.

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Primaquine Plasma Concentration, ng/mL
Plasma concentrations of parent drug
Carboxy-Primaquine Plasma Contration, ng/mL
Plasma concentrations of carboxy-primaquine metabolite
Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL
Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
Primaquine Orthoquinone Plasma concentration, ng/mL
Plasma concentrations of Primaquine Orthoquinone metabolite
Change in Hematocrit (%) compared to baseline
Change in Hematocrit (%) compared to baseline
Change in Hemoglobin (g/dL) compared to baseline
Change in Hemoglobin (g/dL) compared to baseline
Change is AST (U/L) compared to baseline
Change is AST (U/L) compared to baseline; used to monitor liver function
Change in ALT (U/L) compared to baseline
Change in ALT (U/L) compared to baseline; used to monitor liver function
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

Full Information

First Posted
August 27, 2019
Last Updated
October 14, 2020
Sponsor
University of Mississippi, Oxford
Collaborators
University of Colorado, Denver, Southern Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04073953
Brief Title
Primaquine Enantiomers in G6PD Deficient Human Volunteers
Official Title
Metabolism and Pharmacokinetics of Primaquine Enantiomers in G6PD Deficient Human Volunteers Receiving a Five Day Dose Regimen
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
September 1, 2021 (Anticipated)
Study Completion Date
September 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Mississippi, Oxford
Collaborators
University of Colorado, Denver, Southern Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
G6PD Deficiency
Keywords
G6PD, Hemolysis, Primaquine, Pharmacokinetics, Malaria

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RPQ (-) enantiomer
Arm Type
Experimental
Arm Description
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.
Arm Title
SPQ (+) enantiomer
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Cohort 1 will receive placebo capsules every day for 5 days. Cohort 2 will receive placebo capsules every day for five days.
Intervention Type
Drug
Intervention Name(s)
RPQ
Other Intervention Name(s)
R-(-) Enantiomer of Primiquine Phosphate
Intervention Description
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
Intervention Type
Drug
Intervention Name(s)
SPQ
Other Intervention Name(s)
S-(+) Enantiomer of Primaquine Phosphate
Intervention Description
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The study will compare the individual enantiomers of Primaquine -R-(-)-PQ, S-(+)-PQ, and Placebo.
Primary Outcome Measure Information:
Title
Change in Methemoglobin concentration in blood from baseline
Description
Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
Time Frame
Days 0, 3, 5
Secondary Outcome Measure Information:
Title
Primaquine Plasma Concentration, ng/mL
Description
Plasma concentrations of parent drug
Time Frame
Days 0, 3, 5
Title
Carboxy-Primaquine Plasma Contration, ng/mL
Description
Plasma concentrations of carboxy-primaquine metabolite
Time Frame
Days 0, 3, 5
Title
Primaquine N-carbamoyl-glucuronide Plasma contration, ng/mL
Description
Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
Time Frame
Days 0, 3, 5
Title
Primaquine Orthoquinone Plasma concentration, ng/mL
Description
Plasma concentrations of Primaquine Orthoquinone metabolite
Time Frame
Days 0, 3, 5
Title
Change in Hematocrit (%) compared to baseline
Description
Change in Hematocrit (%) compared to baseline
Time Frame
Days 0, 3, 5
Title
Change in Hemoglobin (g/dL) compared to baseline
Description
Change in Hemoglobin (g/dL) compared to baseline
Time Frame
Days 0, 3, 5
Title
Change is AST (U/L) compared to baseline
Description
Change is AST (U/L) compared to baseline; used to monitor liver function
Time Frame
Days 0, 3, 5
Title
Change in ALT (U/L) compared to baseline
Description
Change in ALT (U/L) compared to baseline; used to monitor liver function
Time Frame
Days 0, 3, 5
Title
Change in total Bilirubin (mg/dL) compared to baseline
Description
Change in total Bilirubin (mg/dL) compared to baseline; used to monitor liver function and red cell integrity
Time Frame
Days 0, 3, 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Larry Walker, Ph.D.
Phone
662-915-1005
Email
lwalker@olemiss.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kerri Harrison, RN
Phone
662-915-2103
Email
laharri6@olemiss.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Larry Walker, Ph.D.
Organizational Affiliation
University of Mississippi Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Mississippi
City
University
State/Province
Mississippi
ZIP/Postal Code
38677
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kerri Harrison, RN
Phone
662-915-2103
Email
kaharri6@olemiss.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Primaquine Enantiomers in G6PD Deficient Human Volunteers

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