MalariaPhase 1NCT03934450
Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
A Phase 1 study testing RPQ, SPQ and Primaquine Phosphate in people with Malaria and Glucose 6 Phosphate Dehydrogenase Deficiency, run by University of Mississippi, Oxford at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Glucose 6 Phosphate Dehydrogenase Deficiency
- What is being tested?
- RPQ, SPQ and Primaquine Phosphate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Aug 2018to 1 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Normal, healthy adults aged 18 to 65 years
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Mississippi
University, Mississippi, 38677
About this study
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.
Read the 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.
- Being tested
- RPQ, SPQ, Primaquine Phosphate, Placebo
- Keywords
- Hemolysis, Primaquine, Pharmacokinetics
- Medical subject headings
- Malaria, Glucosephosphate Dehydrogenase Deficiency, Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPQDrug
Also called R-(-) Enantiomer of Primaquine Phosphate
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
SPQDrug
Also called S-(+) Enantiomer of Primaquine Phosphate
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
Primaquine PhosphateDrug
Also called Racemic Primaquine
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
PlaceboDrug
The study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version.
| Study group | Role | What they receive |
|---|---|---|
| RPQ (-) enantiomer | Experimental | 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 Receives: Drug: RPQ |
| SPQ (+) enantiomer | Experimental | 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 Receives: Drug: SPQ |
| Primaquine Phosphate | Active comparator | 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 Receives: Drug: Primaquine Phosphate |
| Placebo | Placebo comparator | Cohort 1 will receive placebo (4A) capsules everyday for seven days Cohort 2 will receive placebo (4A) capsules everyday for seven days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Methemoglobin concentration in blood from baseline
Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
Measured: Days 0, 3, 5, 7
Secondary outcomes (9)
Primaquine Plasma concentration, ng/mL
Plasma concentrations of parent drug
Measured: Days 0, 3, 5, 7
Carboxy- Primaquine Plasma concentration, ng/mL
Plasma concentrations of carboxy-primaquine metabolite
Measured: Days 0, 3, 5, 7
Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL
Plasma concentrations of Primaquine N-carbamoyl-glucuronide metabolite
Measured: Days 0, 3, 5, 7
Primaquine Orthoquinone Plasma concentration, ng/mL
Plasma concentrations of Primaquine Orthoquinone metabolite
Measured: Days 0, 3, 5, 7
Change in Hematocrit (%) Compared to baseline
Change in Hematocrit (%) Compared to baseline
Measured: Days 0, 3, 5, 7
Change in Hemoglobin (g/dL) Compared to baseline
Change in Hemoglobin (g/dL) Compared to baseline
Measured: Days 0, 3, 5, 7
Change in AST (U/L) Compared to baseline
Change in Aspartate aminotransferase (U/L) Compared to baseline; used to monitor liver function
Measured: Days 0, 3, 5, 7
Change in ALT (U/L) Compared to baseline
Change in Alanine aminotransferase (U/L) Compared to baseline; used to monitor liver function
Measured: Days 0, 3, 5, 7
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
Measured: Days 0, 3, 5, 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start17 Aug 2018
- Primary completion1 May 2019
- Study completion1 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Mississippi, Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Larry Walker, Phd, Principal investigator, University of Mississippi Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03934450
- Sponsor's protocol ID
- PQ Study 2
- Status last verified
- May 2019
- First submitted
- 14 May 2018
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers Receiving a Seven Day Dose Regimen
- ClinicalTrials.gov ID
- NCT03934450
- Acronym / sponsor ID
- PQ Study 2
- Keywords
- Hemolysis, Primaquine, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of Mississippi, OxfordUniversity, hospital or other
- Study start
- 17 Aug 2018 (actual)
- Primary completion
- 1 May 2019 (actual)
- Study completion
- 1 May 2019 (actual)
- First posted
- 1 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| RPQ (-) enantiomer | Experimental | Drug: RPQCohort 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 |
| SPQ (+) enantiomer | Experimental | Drug: SPQCohort 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 |
| Primaquine Phosphate | Active comparator | Drug: Primaquine PhosphateCohort 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 |
| Placebo | Placebo comparator | Drug: PlaceboCohort 1 will receive placebo (4A) capsules everyday for seven days Cohort 2 will receive placebo (4A) capsules everyday for seven days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Normal, healthy adults aged 18 to 65 years
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RPQAlso: R-(-) Enantiomer of Primaquine PhosphateThe study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. | Drug | RPQ (-) enantiomer |
| SPQAlso: S-(+) Enantiomer of Primaquine PhosphateThe study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. | Drug | SPQ (+) enantiomer |
| Primaquine PhosphateAlso: Racemic PrimaquineThe study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. | Drug | Primaquine Phosphate |
| PlaceboThe study will compare the individual enantiomers of primaquine - R- (-)-PQ, S-(+)-PQ, and Placebo along with the racemic version. | Drug | Placebo |
Primary outcome
Change in Methemoglobin concentration in blood from baseline
Time frame: Days 0, 3, 5, 7
Change in Methemoglobin concentration in blood from baseline (% hemoglobin)
9 secondary outcomes
Primaquine Plasma concentration, ng/mL
Time frame: Days 0, 3, 5, 7
Carboxy- Primaquine Plasma concentration, ng/mL
Time frame: Days 0, 3, 5, 7
Primaquine N-carbamoyl-glucuronide Plasma concentration, ng/mL
Time frame: Days 0, 3, 5, 7
Primaquine Orthoquinone Plasma concentration, ng/mL
Time frame: Days 0, 3, 5, 7
Change in Hematocrit (%) Compared to baseline
Time frame: Days 0, 3, 5, 7
Change in Hemoglobin (g/dL) Compared to baseline
Time frame: Days 0, 3, 5, 7
Change in AST (U/L) Compared to baseline
Time frame: Days 0, 3, 5, 7
Change in ALT (U/L) Compared to baseline
Time frame: Days 0, 3, 5, 7
Change in Total Bilirubin (mg/dL) Compared to baseline
Time frame: Days 0, 3, 5, 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Larry Walker, Phd principal investigator
University of Mississippi Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RPQ, SPQ and Primaquine Phosphate in people with Malaria and Glucose 6 Phosphate Dehydrogenase Deficiency, run by University of Mississippi, Oxford at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Methemoglobin concentration in blood from baseline (time frame: Days 0, 3, 5, 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019.