HealthyPhase 4NCT02192944
Comparison of the ECG Effects Related to Pharmacokinetic Profile of Chloroquine and Piperaquine
A Phase 4 study testing Chloroquine and Dihydroartemisinin-piperaquine in people with Healthy, run by University of Oxford at 1 site in Thailand.
Trial summary
Chloroquine and piperaquine are the two most widely used antimalarial drugs ever. Hundreds of millions of people have received these drugs. Both are structurally similar and have cardiovascular effect. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Chloroquine and Dihydroartemisinin-piperaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteThailand
- Study dates
- Jul 2014to Sep 2015
- Phase
- Phase 4
- 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
- Male and female subjects 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 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) until study completion.
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- 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, until study completion.
- Normal electrocardiogram (ECG) with QTc < 450 msec.
- Provide a signed and dated written informed consent prior to study participation.
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 hypertension, 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:
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- 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 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.
- 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.
- Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
- AST or ALT >1.5 upper limit of normal (ULN).
- Subjects with history of renal disease, hepatic disease, and/or cholecystectomy.
- Abnormal methaemoglobin level.
- Subjects who have anemia, Hb <12 for both male and female
- History of antimalarial drugs use within 12 months.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Faculty of Tropical Medicine, Mahidol University
Bangkok, 10400
About this study
Official title: Comparison of the Electrocardiographic Effects in Relation to Pharmacokinetic Profile of Chloroquine and Piperaquine in Healthy Thai Subjects
Chloroquine and piperaquine are the two most widely used antimalarial drugs ever. Hundreds of millions of people have received these drugs. Both are structurally similar and have cardiovascular effect. While there are no concerns over the use of chloroquine, regulatory authorities have suggested restrictions on the use of piperaquine.
We have recently completed a series of cross-over clinical and pharmacokinetic evaluations of chloroquine, piperaquine, pyronaridine and primaquine in healthy subjects. These studied were approved by the ethical committee of FTM. All drugs were well tolerated with no clinically significant ECG changes. Four subjects were in two studies. This offers a unique opportunity to compare the electrocardiographic effects of chloroquine and piperaquine in the same subjects and therefore characterize the concentration-effect relationships, and thus relative safety.
We propose to extend the previous subject study to recruit 16 subjects including those who have received either piperaquine or chloroquine in our previous studies so that 20 subjects received both drugs for a crossover comparison. The blood sampling schedule and electrocardiograms would be exactly the same as previously but would finish at 24 hours.
Read the detailed description
The investigator team has recently completed two cross-over clinical and pharmacokinetic evaluations chloroquine and piperaquine in healthy subjects i.e. Study A and Study B.
Study A: Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Chloroquine in Healthy Thai Adult Subjects
Study B: Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Dihydroartemisinin-Piperaquine in Healthy Adult Subjects
Four subjects were in both studies. The investigator proposes to extend the previous subject study to recruit 16 subjects including but not limited to those who have received either chloroquine from study A or piperaquine form study B in our previous studies so that 20 subjects received both drugs for a crossover comparison.
Subjects who were previously enrolled into study A that received a single dose of 600 mg chloroquine base will receive a single dose of piperaquine phosphate (in form of 120/960 mg dihydroartemisinin-piperaquine) in this study. The subjects who were previously enrolled into study B that received a single dose of piperaquine phosphate (in form of 120/960 mg dihydroartemisinin-piperaquine) will receive a single dose of 600 mg of chloroquine base in this study.
The investigator team may recruit naive subject in case, the team can't reach total number of 20 subjects.
The total duration for each subject's participation in the study is approximately 3 weeks for subject who challenges only one study drug or 11 weeks for subject who challenges both drugs.
- Conditions
- Healthy
- Being tested
- Chloroquine, Dihydroartemisinin-piperaquine
- Keywords
- ECG, Pharmacokinetic profile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChloroquineDrug
Chloroquine base 600 mg single dose. To monitor ECG 12 lead at 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours after dosing.
Dihydroartemisinin-piperaquineDrug
Dihydroartemisinin-piperaquine 120/960 mg single dose To monitor ECG 12 lead at: 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours after dosing.
| Study group | Role | What they receive |
|---|---|---|
| Chloroquine | Active comparator | Chloroquine base 600 mg single dose Receives: Drug: Dihydroartemisinin-piperaquine |
| Dihydroartemisinin-piperaquine | Active comparator | Dihydroartemisinin-piperaquine 120/960 mg single dose Receives: Drug: Chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of QTc within 24 hours after dosing
Measured: 24 hours after dosing
Area under the curve
Area under the curve within 24 hours after dosing
Measured: 24 hours after dosing
Secondary outcomes (1)
Number of participant with adverse event
Measured: 24 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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 4
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Borimas Hanboonkunupakarn, MD, Principal investigator, Faculty of Tropical Medicine, Mahidol University, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02192944
- Sponsor's protocol ID
- FTM1401
- Status last verified
- Nov 2015
- First submitted
- 1 Jul 2014
- Last updated
- 3 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Electrocardiographic Effects in Relation to Pharmacokinetic Profile of Chloroquine and Piperaquine in Healthy Thai Subjects
- ClinicalTrials.gov ID
- NCT02192944
- Acronym / sponsor ID
- FTM1401
- Conditions
- Healthy
- Keywords
- ECG, Pharmacokinetic profile
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 17 Jul 2014 (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.
Chloroquine and piperaquine are the two most widely used antimalarial drugs ever. Hundreds of millions of people have received these drugs. Both are structurally similar and have cardiovascular effect. While there are no concerns over the use of chloroquine, regulatory authorities have suggested restrictions on the use of piperaquine.
We have recently completed a series of cross-over clinical and pharmacokinetic evaluations of chloroquine, piperaquine, pyronaridine and primaquine in healthy subjects. These studied were approved by the ethical committee of FTM. All drugs were well tolerated with no clinically significant ECG changes. Four subjects were in two studies. This offers a unique opportunity to compare the electrocardiographic effects of chloroquine and piperaquine in the same subjects and therefore characterize the concentration-effect relationships, and thus relative safety.
We propose to extend the previous subject study to recruit 16 subjects including those who have received either piperaquine or chloroquine in our previous studies so that 20 subjects received both drugs for a crossover comparison. The blood sampling schedule and electrocardiograms would be exactly the same as previously but would finish at 24 hours.
Detailed description
The investigator team has recently completed two cross-over clinical and pharmacokinetic evaluations chloroquine and piperaquine in healthy subjects i.e. Study A and Study B.
Study A: Phase 1, Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Chloroquine in Healthy Thai Adult Subjects
Study B: Open-Label Study to Evaluate Potential Pharmacokinetic Interaction of Orally Administered Primaquine and Dihydroartemisinin-Piperaquine in Healthy Adult Subjects
Four subjects were in both studies. The investigator proposes to extend the previous subject study to recruit 16 subjects including but not limited to those who have received either chloroquine from study A or piperaquine form study B in our previous studies so that 20 subjects received both drugs for a crossover comparison.
Subjects who were previously enrolled into study A that received a single dose of 600 mg chloroquine base will receive a single dose of piperaquine phosphate (in form of 120/960 mg dihydroartemisinin-piperaquine) in this study. The subjects who were previously enrolled into study B that received a single dose of piperaquine phosphate (in form of 120/960 mg dihydroartemisinin-piperaquine) will receive a single dose of 600 mg of chloroquine base in this study.
The investigator team may recruit naive subject in case, the team can't reach total number of 20 subjects.
The total duration for each subject's participation in the study is approximately 3 weeks for subject who challenges only one study drug or 11 weeks for subject who challenges both drugs.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chloroquine | Active comparator | Drug: Dihydroartemisinin-piperaquineChloroquine base 600 mg single dose |
| Dihydroartemisinin-piperaquine | Active comparator | Drug: ChloroquineDihydroartemisinin-piperaquine 120/960 mg single dose |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination
- Male and female subjects aged between 18 years to 60 years.
- A female is eligible to enter and participate in this study if she is:
- 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, until study completion.
- Normal electrocardiogram (ECG) with QTc < 450 msec.
Key exclusion criteria (19 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 hypertension, 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 |
|---|---|---|
| ChloroquineChloroquine base 600 mg single dose. To monitor ECG 12 lead at 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours after dosing. | Drug | Dihydroartemisinin-piperaquine |
| Dihydroartemisinin-piperaquineDihydroartemisinin-piperaquine 120/960 mg single dose To monitor ECG 12 lead at: 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours after dosing. | Drug | Chloroquine |
Primary outcome
Changes of QTc within 24 hours after dosing
Time frame: 24 hours after dosing
Area under the curve
Time frame: 24 hours after dosing
Area under the curve within 24 hours after dosing
1 secondary outcome
Number of participant with adverse event
Time frame: 24 hours after dosing
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 3 Nov 2015.
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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.
Borimas Hanboonkunupakarn, MD principal investigator
Faculty of Tropical Medicine, Mahidol University, Thailand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Chloroquine and Dihydroartemisinin-piperaquine in people with Healthy, 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 9 inclusion and 19 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 3 Nov 2015. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Changes of QTc within 24 hours after dosing (time frame: 24 hours after dosing). The study lists 2 primary outcomes in all. 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 3 Nov 2015.