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

Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03934450
• Other study ID #: PQ Study 2
• Status: Completed
• Phase: Phase 1
• Start date: August 17, 2018
• Est. completion date: May 1, 2019

Study information

• Verified date: May 2019
• Source: University of Mississippi, Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. Based on the results of this study, if one enantiomer seems to show a better safety profile (in terms of hematological effects), an analogous study will be carried out in G6PD deficient individuals (under a separate protocol). The studies are primarily aimed at understanding the tolerability and safety of the enantiomers in G6PD deficiency. If one shows a better safety profile, ultimately the evaluation of its efficacy will be required.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 1, 2019
• Est. primary completion date: May 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Normal, healthy adults aged 18 to 65 years

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Glucose 6 Phosphate Dehydrogenase Deficiency
• Glucosephosphate Dehydrogenase Deficiency
• Malaria

Intervention

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

Locations

Country	Name	City	State
United States	University of Mississippi	University	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
University of Mississippi, Oxford

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, 7
Secondary	Primaquine Plasma concentration, ng/mL	Plasma concentrations of parent drug	Days 0, 3, 5, 7
Secondary	Carboxy- Primaquine Plasma concentration, ng/mL	Plasma concentrations of carboxy-primaquine metabolite	Days 0, 3, 5, 7
Secondary	Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL	Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite	Days 0, 3, 5, 7
Secondary	Primaquine Orthoquinone Plasma concentration, ng/mL	Plasma concentrations of Primaquine Orthoquinone metabolite	Days 0, 3, 5, 7
Secondary	Change in Hematocrit (%) Compared to baseline	Change in Hematocrit (%) Compared to baseline	Days 0, 3, 5, 7
Secondary	Change in Hemoglobin (g/dL) Compared to baseline	Change in Hemoglobin (g/dL) Compared to baseline	Days 0, 3, 5, 7
Secondary	Change in AST (U/L) Compared to baseline	Change in Aspartate aminotransferase (U/L) Compared to baseline; used to monitor liver function	Days 0, 3, 5, 7
Secondary	Change in ALT (U/L) Compared to baseline	Change in Alanine aminotransferase (U/L) Compared to baseline; used to monitor liver function	Days 0, 3, 5, 7
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, 7