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出境医 / 临床实验 / Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Malaria Glucose 6 Phosphate Dehydrogenase Deficiency | Drug: RPQ Drug: SPQ Drug: Primaquine Phosphate Drug: Placebo | Phase 1 |
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. 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.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 36 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Crossover Assignment |
| Intervention Model Description: | 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. |
| Masking: | Single (Participant) |
| Masking Description: | Participants will not be able to know the sequence of the drug adminstration |
| Primary Purpose: | Basic Science |
| Official Title: | Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen |
| Actual Study Start Date : | August 17, 2018 |
| Actual Primary Completion Date : | May 1, 2019 |
| Actual Study Completion Date : | May 1, 2019 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
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Experimental: RPQ (-) enantiomer
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
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Drug: RPQ
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
Other Name: R-(-) Enantiomer of Primaquine Phosphate
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Experimental: SPQ (+) enantiomer
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
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Drug: SPQ
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
Other Name: S-(+) Enantiomer of Primaquine Phosphate
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Active Comparator: Primaquine Phosphate
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
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Drug: Primaquine Phosphate
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
Other Name: Racemic Primaquine
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Placebo Comparator: Placebo
Cohort 1 will receive placebo (4A) capsules everyday for seven days Cohort 2 will receive placebo (4A) capsules everyday for seven days
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Drug: Placebo
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
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Outcome Measures
Primary Outcome Measures :
- Change in Methemoglobin concentration in blood from baseline [ Time Frame: Days 0, 3, 5, 7 ]Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
Secondary Outcome Measures :
- Primaquine Plasma concentration, ng/mL [ Time Frame: Days 0, 3, 5, 7 ]Plasma concentrations of parent drug
- Carboxy- Primaquine Plasma concentration, ng/mL [ Time Frame: Days 0, 3, 5, 7 ]Plasma concentrations of carboxy-primaquine metabolite
- Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL [ Time Frame: Days 0, 3, 5, 7 ]Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
- Primaquine Orthoquinone Plasma concentration, ng/mL [ Time Frame: Days 0, 3, 5, 7 ]Plasma concentrations of Primaquine Orthoquinone metabolite
- Change in Hematocrit (%) Compared to baseline [ Time Frame: Days 0, 3, 5, 7 ]Change in Hematocrit (%) Compared to baseline
- Change in Hemoglobin (g/dL) Compared to baseline [ Time Frame: Days 0, 3, 5, 7 ]Change in Hemoglobin (g/dL) Compared to baseline
- Change in AST (U/L) Compared to baseline [ Time Frame: Days 0, 3, 5, 7 ]Change in Aspartate aminotransferase (U/L) Compared to baseline; used to monitor liver function
- Change in ALT (U/L) Compared to baseline [ Time Frame: Days 0, 3, 5, 7 ]Change in Alanine aminotransferase (U/L) Compared to baseline; used to monitor liver function
- Change in Total Bilirubin (mg/dL) Compared to baseline [ Time Frame: Days 0, 3, 5, 7 ]Change in Total Bilirubin (mg/dL) Compared to baseline; used to monitor liver function and red cell integrity
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
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.
Contacts and Locations
Locations
| United States, Mississippi | |
| University of Mississippi | |
| University, Mississippi, United States, 38677 | |
Sponsors and Collaborators
University of Mississippi, Oxford
Investigators
| Principal Investigator: | Larry Walker, Phd | University of Mississippi Medical Center |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 14, 2018 | ||||
| First Posted Date ICMJE | May 1, 2019 | ||||
| Last Update Posted Date | May 14, 2019 | ||||
| Actual Study Start Date ICMJE | August 17, 2018 | ||||
| Actual Primary Completion Date | May 1, 2019 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Change in Methemoglobin concentration in blood from baseline [ Time Frame: Days 0, 3, 5, 7 ] Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen | ||||
| Official Title ICMJE | Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen | ||||
| 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. | ||||
| 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. 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. | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 1 | ||||
| Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Crossover Assignment Intervention Model Description: 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. Masking Description: Participants will not be able to know the sequence of the drug adminstration Primary Purpose: Basic Science
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| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Actual Enrollment ICMJE |
36 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Actual Study Completion Date ICMJE | May 1, 2019 | ||||
| Actual Primary Completion Date | May 1, 2019 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 65 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | Yes | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | United States | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03934450 | ||||
| Other Study ID Numbers ICMJE | PQ Study 2 | ||||
| Has Data Monitoring Committee | Yes | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | University of Mississippi, Oxford | ||||
| Study Sponsor ICMJE | University of Mississippi, Oxford | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | University of Mississippi, Oxford | ||||
| Verification Date | May 2019 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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