Ignite Creation Date:
2025-12-25 @ 12:35 AM
Ignite Modification Date:
2026-02-20 @ 8:08 PM
Study NCT ID:
NCT02535767
Status:
COMPLETED
Last Update Posted:
2017-02-06
First Post:
2015-08-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Determining a Tolerable Dose of Primaquine in G6PD-deficient Persons Without Malaria in Mali
Sponsor:
University of California, San Francisco
Organization:
Study Overview
Official Title:
Determining a Tolerable Dose of Primaquine in G6PD-deficient Persons Without Malaria in Mali
Status:
COMPLETED
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PQSAFETY
Brief Summary:
The purpose of this study is to determine the highest tolerable dose of primaquine within 0.75 mg/kg. A tolerable dose is defined as one in which:
* Two or fewer participants (\< 30%) experience hemolysis;
* No participant experiences a drug-related serious adverse event; and
* No participant requires a blood transfusion.
* Two or fewer participants (\< 30%) experience hemolysis;
* No participant experiences a drug-related serious adverse event; and
* No participant requires a blood transfusion.
Detailed Description:
Purpose: The purpose of this study is to determine the highest tolerable dose of primaquine within 0.75 mg/kg. A tolerable dose is defined as one in which:
* Two or fewer participants (\< 30%) experience hemolysis;
* No participant experiences a drug-related serious adverse event; and
* No participant requires a blood transfusion.
Design:
* This is an open-label, phase 2, dose-adjustment study.
* The initial primaquine dose will be 0.40 mg/kg. Subsequent dose groups will be selected depending on the occurrence of adverse events in the previous dose group. Once the highest tolerable dose in G6PD-deficient (G6PDd) individuals is established, a control group of G6PD normal malaria-free men will be enrolled and evaluated under the highest tolerable dose of primaquine.
Study Population:
* Malian men aged 18-50 years without malaria infection.
* The majority of study participants will be G6PDd.
Study Size: This study will enroll 7 participants per dose group. If all dose groups are tested, this study will enroll approximately 28 participants.
Study visit and duration:
* Each participant will be followed for 28 days.
* Participants will be evaluated for hemolysis and adverse events on Days 1-10, 14, and 28 following their assigned primaquine dose.
Primary objective:
To measure the change in hemoglobin among G6PD deficient west-African men following a single low-dose of primaquine not to exceed 0.75 mg/kg.
Secondary objectives:
1. To measure the occurrence of adverse events, graded by severity, at each primaquine dose among G6PD deficient men
2. To measure the occurrence of markers of acute hemolytic anemia (AHA), at each primaquine dose among G6PD deficient men. AHA markers will include:
* Absolute and fractional change in hemoglobin on day 7 vs. baseline
* Urine color
* Reticulocyte count
* Bilirubin (both total and direct)
* Methemoglobin concentration
* Development of physical signs or symptoms of hemolytic anemia
3. To compare the change in hemoglobin, frequency and severity of adverse events, and occurrence of markers of AHA between G6PD deficient and non-deficient participants receiving the highest tolerable primaquine dose
4. To measure G6PD enzyme activity (semiquantitative testing, U / gHb)
5. To measure the pharmacokinetics of primaquine, carboxyprimaquine, and other metabolites according to plasma concentrations.
6. To genotype participant blood samples for cytochrome P450 2D6 (CYP2D6) single nucleotide polymorphisms (SNPs), to determine if potential hemolysis in G6PDd individuals is affected by CYP2D6 metabolizer status (e.g. weak metabolizers and/or intermediate metabolizers)
* Two or fewer participants (\< 30%) experience hemolysis;
* No participant experiences a drug-related serious adverse event; and
* No participant requires a blood transfusion.
Design:
* This is an open-label, phase 2, dose-adjustment study.
* The initial primaquine dose will be 0.40 mg/kg. Subsequent dose groups will be selected depending on the occurrence of adverse events in the previous dose group. Once the highest tolerable dose in G6PD-deficient (G6PDd) individuals is established, a control group of G6PD normal malaria-free men will be enrolled and evaluated under the highest tolerable dose of primaquine.
Study Population:
* Malian men aged 18-50 years without malaria infection.
* The majority of study participants will be G6PDd.
Study Size: This study will enroll 7 participants per dose group. If all dose groups are tested, this study will enroll approximately 28 participants.
Study visit and duration:
* Each participant will be followed for 28 days.
* Participants will be evaluated for hemolysis and adverse events on Days 1-10, 14, and 28 following their assigned primaquine dose.
Primary objective:
To measure the change in hemoglobin among G6PD deficient west-African men following a single low-dose of primaquine not to exceed 0.75 mg/kg.
Secondary objectives:
1. To measure the occurrence of adverse events, graded by severity, at each primaquine dose among G6PD deficient men
2. To measure the occurrence of markers of acute hemolytic anemia (AHA), at each primaquine dose among G6PD deficient men. AHA markers will include:
* Absolute and fractional change in hemoglobin on day 7 vs. baseline
* Urine color
* Reticulocyte count
* Bilirubin (both total and direct)
* Methemoglobin concentration
* Development of physical signs or symptoms of hemolytic anemia
3. To compare the change in hemoglobin, frequency and severity of adverse events, and occurrence of markers of AHA between G6PD deficient and non-deficient participants receiving the highest tolerable primaquine dose
4. To measure G6PD enzyme activity (semiquantitative testing, U / gHb)
5. To measure the pharmacokinetics of primaquine, carboxyprimaquine, and other metabolites according to plasma concentrations.
6. To genotype participant blood samples for cytochrome P450 2D6 (CYP2D6) single nucleotide polymorphisms (SNPs), to determine if potential hemolysis in G6PDd individuals is affected by CYP2D6 metabolizer status (e.g. weak metabolizers and/or intermediate metabolizers)
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: