Vivax MalariaPhase 1PQCQNCT01218932
Pharmacokinetic Study of Primaquine and Chloroquine in Healthy Subjects
A Phase 1 study testing A and B in people with Vivax Malaria, run by University of Oxford at 1 site in Thailand.
Trial summary
This is a standard pharmacokinetic interaction study. Subjects will be randomized to be either group A or B. Group A. Subjects will have 3 hospitalizations to complete. Each hospitalization will be about 12-24 hours depends on each regimen. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Vivax Malaria
- What is being tested?
- A and B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteThailand
- Study dates
- Oct 2010to Mar 2012
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
- Males and Females aged between 18 years to 60 years.
- A female is eligible to enter and participate in this study if she is: of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy or of childbearing potential, has a negative serum pregnancy test at screening and urine pregnancy test prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures
- A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
- Read, comprehend, and write at a sufficient level to complete study-related materials.
- Provide a signed and dated written informed consent prior to study participation.
- Normal electrocardiogram (ECG) with QTc <450 msec.
- Willingness and ability to comply with the study protocol for the duration of the trial.
Who cannot join
- Females who are pregnant, trying to get pregnant, or are lactating.
- The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.
- A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
- Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points (heart failure, hypokalemia).
- Subjects with a family history of sudden cardiac death.
- A creatinine clearance <70 mL/min as determined by Cockcroft-Gault equation:
Show all 22Show fewer
- CLcr (mL/min) = (140 - age) Wt / (72 Scr) (multiply answer by 0.85 for females) Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dL [Cockcroft, 1976].
- History of alcohol or substance abuse or dependence within 6 months of the study: History of regular alcohol consumption averaging >7 drinks/wk for women or >14 drinks/wk for men. One drink is equivalent to 12 g alcohol = 5 oz (150 mL) of wine or 12 oz (360 mL) of beer or 1.5 oz (45 mL) of 80 proof distilled spirits within 6 months of screening.
- Use of prescription or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise subject safety; the investigator will take advice from the manufacturer representative as necessary.
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
- The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample during each regimen.
- Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Note: This does not include plasma donation.
- Subjects who have a history of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- Subjects with unstable medical conditions that, in the opinion of the investigator would compromise their participation in the trial
- Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
- Lack of suitability for participation in this study, for any reason, in the opinion of the investigator.
- AST or ALT >1.5 upper limit of normal (ULN)
- Subjects with history of renal disease, hepatic disease, and/or cholecystectomy
- G6PD deficient.
- Abnormal methaemoglobin level.
- Subjects who have anemia, Hb <12 for both male and female
- History of malaria treatment with Primaquine and/or Chloroquine within 12 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Chloroquine in Healthy Thai Adult Subjects
This is a standard pharmacokinetic interaction study. Subjects will be randomized to be either group A or B. Group A. Subjects will have 3 hospitalizations to complete. Each hospitalization will be about 12-24 hours depends on each regimen. Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period.
Subjects in B group who receive regimen 1 of primaquine (PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission(visit 4) with 8 week wash out period in between.
Read the detailed description
Chloroquine and primaquine, has been first therapy for Plasmodium vivax and ovale malaria for over 50 years, and has been part of National policy in Thailand for decades. Primaquine is the only available hypnozoitocidal drug for P.vivax and gametocytocidal agent for Plasmodium falciparum malaria. Despite this enormous use knowledge about the mechanism of activity, pharmacokinetic properties, resistance and toxicity of primaquine are limited. Primaquine at the previously used dose for radical cure (15 mg base/day for 14 days) is also weakly effective against asexual stages of P. vivax malaria [4] The higher dose of 30 mg daily evaluated for malaria prophylaxis is now also generally recommended for radical cure. In the standard radical cure regimen, primaquine is usually given after the 3-day course of chloroquine, but there has been no study to inform timing of dosing so this decision is arbitrary. Despite the multistage specificity against the malaria parasite, and extensive recommendations, primaquine is currently underused because of uncertainties over safety, efficacy and dosage. Primaquine is an oxidant drug and causes haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Although several studies of the metabolites of the primaquine and chloroquine have been conducted over the past few years remarkably little is known about the interaction between these two commonly coadministered drugs.
This study is open-label pharmacokinetic study. Healthy 16 volunteers will be recruited to the established volunteer facility at single site at the Hospital for Tropical Diseases to determine the pharmacokinetic properties of primaquine and it's main active metabolites and evaluate any interaction with chloroquine.in order to provide clinical guidance for the optimum primaquine/chloroquine treatment regimens.
- Conditions
- Vivax Malaria
- Being tested
- A, B
- Keywords
- primaquine, chloroquine, pharmacokinetic, interactions
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADrug
Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period.
BDrug
Subjects in B group who receive regimen 1 of primaquine ( PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission( visit 4) with 8 week wash out period in between.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Primaquine only, followed by chloroquine/primaquine, followed by chloroquine only Receives: Drug: A |
| B | Active comparator | Primaquine alone, followed by chloroquine, followed by chloroquine/primaquine Receives: Drug: B |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
Area under the plasma concentration time AUC 0-∞curve for primaquine and metabolites (mPQ) when given alone and together with chloroquine
Measured: 36 days
Secondary outcomes (4)
Cmax
Primaquine and metabolites maximum concentrations, chloroquine and metabolites maximum concentration and AUC
Measured: 36 days
Elimination rate
Primaquine and metabolites (mPQ) elimination rate constants (mPQ-λz), and elimination half life (mPQ-t1/2),chloroquine metabolite(s) elimination rate constant (mCQ-λz), and elimination half life (mCQ-t1/2)
Measured: 36 days
Adverse events
Safety and tolerability parameters, including adverse events, clinical laboratory, and vital signs assessments
Measured: 36 days
Pharmacogenetics
Pharmacogenetic polymorphisms in the case of unusually high or low drug levels
Measured: 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2011
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vivax MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University
- Responsible party
- Sponsor
- Investigators
- Podjanee Jittamala, MD, Principal investigator, Mahidol Oxford Tropical Medicine Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01218932
- Sponsor's protocol ID
- FTM1001
- Acronym
- PQCQ
- Status last verified
- Jun 2012
- First submitted
- 8 Oct 2010
- Last updated
- 14 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Pukrittayakamee S, Tarning J, Jittamala P, Charunwatthana P, Lawpoolsri S, Lee SJ, Hanpithakpong W, Hanboonkunupakarn B, Day NP, Ashley EA, White NJ. Pharmacokinetic interactions between primaquine and chloroquine. Antimicrob Agents Chemother. 2014 Jun;58(6):3354-9. doi: 10.1128/AAC.02794-13. Epub 2014 Mar 31.
PubMed 24687509
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Chloroquine in Healthy Thai Adult Subjects
- ClinicalTrials.gov ID
- NCT01218932
- Acronym / sponsor ID
- PQCQ / FTM1001
- Conditions
- Vivax Malaria
- Keywords
- primaquine, chloroquine, pharmacokinetic, interactions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol University
- Study start
- Oct 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 11 Oct 2010 (estimated)
- 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.
This is a standard pharmacokinetic interaction study. Subjects will be randomized to be either group A or B. Group A. Subjects will have 3 hospitalizations to complete. Each hospitalization will be about 12-24 hours depends on each regimen. Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period.
Subjects in B group who receive regimen 1 of primaquine (PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission(visit 4) with 8 week wash out period in between.
Detailed description
Chloroquine and primaquine, has been first therapy for Plasmodium vivax and ovale malaria for over 50 years, and has been part of National policy in Thailand for decades. Primaquine is the only available hypnozoitocidal drug for P.vivax and gametocytocidal agent for Plasmodium falciparum malaria. Despite this enormous use knowledge about the mechanism of activity, pharmacokinetic properties, resistance and toxicity of primaquine are limited. Primaquine at the previously used dose for radical cure (15 mg base/day for 14 days) is also weakly effective against asexual stages of P. vivax malaria [4] The higher dose of 30 mg daily evaluated for malaria prophylaxis is now also generally recommended for radical cure. In the standard radical cure regimen, primaquine is usually given after the 3-day course of chloroquine, but there has been no study to inform timing of dosing so this decision is arbitrary. Despite the multistage specificity against the malaria parasite, and extensive recommendations, primaquine is currently underused because of uncertainties over safety, efficacy and dosage. Primaquine is an oxidant drug and causes haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Although several studies of the metabolites of the primaquine and chloroquine have been conducted over the past few years remarkably little is known about the interaction between these two commonly coadministered drugs.
This study is open-label pharmacokinetic study. Healthy 16 volunteers will be recruited to the established volunteer facility at single site at the Hospital for Tropical Diseases to determine the pharmacokinetic properties of primaquine and it's main active metabolites and evaluate any interaction with chloroquine.in order to provide clinical guidance for the optimum primaquine/chloroquine treatment regimens.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: APrimaquine only, followed by chloroquine/primaquine, followed by chloroquine only |
| B | Active comparator | Drug: BPrimaquine alone, followed by chloroquine, followed by chloroquine/primaquine |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
- Males and Females aged between 18 years to 60 years.
- A female is eligible to enter and participate in this study if she is: of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy or of childbearing potential, has a negative serum pregnancy test at screening and urine pregnancy test prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures
- A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
- Read, comprehend, and write at a sufficient level to complete study-related materials.
Key exclusion criteria (22 listed)
- Females who are pregnant, trying to get pregnant, or are lactating.
- The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.
- A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
- Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points (heart failure, hypokalemia).
- Subjects with a family history of sudden cardiac death.
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 |
|---|---|---|
| ASubjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period. | Drug | A |
| BSubjects in B group who receive regimen 1 of primaquine ( PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission( visit 4) with 8 week wash out period in between. | Drug | B |
Primary outcome
AUC
Time frame: 36 days
Area under the plasma concentration time AUC 0-∞curve for primaquine and metabolites (mPQ) when given alone and together with chloroquine
4 secondary outcomes
Cmax
Time frame: 36 days
Elimination rate
Time frame: 36 days
Adverse events
Time frame: 36 days
Pharmacogenetics
Time frame: 36 days
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 Jun 2012.
- Derived from this study: PubMed 24687509Pukrittayakamee S, Tarning J, Jittamala P, Charunwatthana P, Lawpoolsri S, Lee SJ, Hanpithakpong W, Hanboonkunupakarn B, Day NP, Ashley EA, White NJ. Pharmacokinetic interactions between primaquine and chloroquine. Antimicrob Agents Chemother. 2014 Jun;58(6):3354-9. doi: 10.1128/AAC.02794-13. Epub 2014 Mar 31.
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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.
Podjanee Jittamala, MD principal investigator
Mahidol Oxford Tropical Medicine Research Unit
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 A and B in people with Vivax Malaria, run by University of Oxford at 1 site in Thailand.
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 8 inclusion and 22 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 Jun 2012. 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 Thailand. 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. 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?
AUC (time frame: 36 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01218932, which also lists 1 linked publication.
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 Jun 2012.