PharmacokineticPhase 1/2ALAQPQNCT02696954
Study of Artemether-lumefantrine, Amodiaquine and Primaquine in Healthy Subjects
A Phase 1/2 study testing Artemether-lumefantrine, Amodiaquine and Artemether-lumefantrine + Amodiaquine in people with Pharmacokinetic and Drug Combination, run by University of Oxford at 1 site in Thailand.
Trial summary
Primary Objective To characterize the potential pharmacokinetic interactions of artemether -lumefantrine, amodiaquine and primaquine in healthy adult subjects. Secondary Objectives To characterize the pharmacokinetic properties of artemether-lumefantrine, amodiaquine and primaquine when given alone and in combination. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetic, Drug Combination, Healthy
- What is being tested?
- Artemether-lumefantrine, Amodiaquine and Artemether-lumefantrine + Amodiaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteThailand
- Study dates
- 18 Nov 2016to Mar 2019
- Phase
- Phase 1/2
- 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 or female non-smoker 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) during the study until completion of the follow-up procedures
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- A male is eligible to enter and participate in this study if he: agrees to abstain from 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.
- 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 pointes (heart failure, hypokalemia) or with a family history of sudden cardiac death.
- A creatinine clearance <70 mL/min as determined by Cockcroft-Gault equation:
- 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].
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- History of alcohol or substance abuse or dependence within 6 months of the study.
- 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 times the drug half-life (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 x half-life, 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.
- Lack of suitability for participation in this study, including but not limited to, unstable medical conditions, systemic disease manifested by tendency to granulocytopenia e.g. rheumatoid arthritis and lupus erythematosus that in the opinion of the investigator would compromise their participation in the trial.
- AST or ALT >1.5 upper limit of normal (ULN)
- Subjects with history of renal disease, hepatic disease, and/or cholecystectomy
- G6PD deficient
- Abnormal methemoglobin level (more than 3 mg/dL).
- History of antimalarial drugs use including but not limited to mefloquine, chloroquine, primaquine, artesunate, piperaquine and pyronaridine treatment within 6 months.
- Subject who received quinacrine in last 30 days.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Faculty of Tropical Medicine, Mahidol University
Bangkok, 10400
About this study
Official title: A Randomized, Open-Label Study to Evaluate Potential Pharmacokinetic Interactions of Orally Administered Artemether-lumefantrine, Amodiaquine and Primaquine in Healthy Adult Subjects
Primary Objective
- To characterize the potential pharmacokinetic interactions of artemether -lumefantrine, amodiaquine and primaquine in healthy adult subjects.
Secondary Objectives
- To characterize the pharmacokinetic properties of artemether-lumefantrine, amodiaquine and primaquine when given alone and in combination.
- To evaluate the safety and tolerability of co-administered artemether-lumefantrine, amodiaquine and primaquine.
- To investigate pharmacogenetic polymorphisms affecting drug levels of artemether-lumefantrine, amodiaquine and primaquine and their metabolites.
Read the detailed description
The study design is an open-label pharmacokinetic study in healthy G6PD normal Thai subjects. This study will enroll 16 healthy subjects. Participants who pass the screening process will have 6 admissions in the hospital to receive 6 drug regimens as below
First admission visit: The subject may be randomized to receive either Artemether-Lumefantrine or Amodiaquine with more than 6 weeks washout period before second admission visit.
Second admission visit: Subject who receives Artemether-Lumefantrine from previous visit will receive amodiaquine in this visit and vice versa. This visit will required more than 6 weeks washout period before third admission visit.
Third admission visit: Every subject will receive Artemether-lumefantrine and Amodiaquine with more than 6 weeks washout period before forth admission visit.
Forth admission visit: Every subject will receive Primaquine with more than 1 week washout period before fifth admission visit.
Fifth admission visit: Subject may randomize to receive either Artemether-Lumefantrine and Primaquine or Artemether-Lumefantrine and Amodiaquine and Primaquine in this visit with more than 6 weeks washout period before sixth admission visit.
Sixth admission visit: Subject who receives Artemether-Lumefantrine and Amodiaquine and primaquine from previous visit will receive Artemether-Lumefantrine and Primaquine in this visit and vice versa.
- Conditions
- Pharmacokinetic, Drug Combination, Healthy
- Being tested
- Artemether-lumefantrine, Amodiaquine, Artemether-lumefantrine + Amodiaquine, Primaquine, Artemether-lumefantrine + Primaquine
- Keywords
- Artemether-lumefantrine, Amodiaquine, Primaquine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrineDrug
Artemether-lumefantrine on Day 0, 1 and 2 Washout period: more than 6 weeks
AmodiaquineDrug
Amodiaquine on Day 0, 1 and 2 Washout period: more than 6 weeks
Artemether-lumefantrineDrug
Artemether-lumefantrine on Day 0, 1 and 2 Washout period: more than 6 weeks
Artemether-lumefantrine + AmodiaquineDrug
Artemether-lumefantrine + Amodiaquine on Day 0, 1 and 2 Washout period: more than 6 weeks
PrimaquineDrug
Primaquine on Day 0 Washout period: more than 1 week
Artemether-lumefantrine + PrimaquineDrug
Artemether-lumefantrine on Day 0, 1 and 2 + Primaquine on Day 0 Washout period: more than 6 weeks
Artemether-lumefantrine + Amodiaquine + PrimaquineDrug
Artemether-lumefantrine Day 0, 1 and 2 + Amodiaquine on Day 0, 1 and 2 + Primaquine on Day 0 Washout period: more than 6 weeks
Artemether-lumefantrine + PrimaquineDrug
Artemether-lumefantrine on Day 0, 1 and 2 + Primaquine on Day 0
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Not described Receives: Drug: Artemether-lumefantrine; Drug: Amodiaquine; Drug: Artemether-lumefantrine + Amodiaquine; Drug: Primaquine; Drug: Artemether-lumefantrine + Primaquine; Drug: Artemether-lumefantrine + Amodiaquine + Primaquine |
| Group B | Experimental | Not described Receives: Drug: Amodiaquine; Drug: Artemether-lumefantrine; Drug: Artemether-lumefantrine + Amodiaquine; Drug: Primaquine; Drug: Artemether-lumefantrine + Amodiaquine + Primaquine; Drug: Artemether-lumefantrine + Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-time curve (AUC (0-∞)
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Measured: 1 year
Area under the concentration-time curve AUC (0-last)
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Measured: 1 year
Maximal concentration (Cmax)
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Measured: 1 year
Secondary outcomes (8)
Elimination clearance (CL/F)
of artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Measured: 1 year
Terminal elimination half-life (t1/2)
of artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Measured: 1 year
Apparent volume of distribution (Vd)
of artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Measured: 1 year
Number of adverse events
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Measured: 1 year
Number of event concerning of abnormal electrocardiographic
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Measured: 1 year
Number of event concerning of abnormal vital signs
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Measured: 1 year
Number of event concerning of abnormal laboratory values
Safety and tolerability parameters including adverse events, electrocardiographic changes, vital signs and biochemical assessments.
Measured: 1 year
Identify polymorphisms of cytochrome 450
To identify polymorphisms of cytochrome 450 related to drug metabolism from individual subject.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2016 (estimated)
- Study start18 Nov 2016
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University, Mahidol Oxford Tropical Medicine Research Unit
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02696954
- Sponsor's protocol ID
- ALAQPQ
- Acronym
- ALAQPQ
- Status last verified
- May 2019
- First submitted
- 18 Feb 2016
- Last updated
- 28 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label Study to Evaluate Potential Pharmacokinetic Interactions of Orally Administered Artemether-lumefantrine, Amodiaquine and Primaquine in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02696954
- Acronym / sponsor ID
- ALAQPQ / ALAQPQ
- Conditions
- Pharmacokinetic, Drug Combination, Healthy
- Keywords
- Artemether-lumefantrine, Amodiaquine, Primaquine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol University, Mahidol Oxford Tropical Medicine Research Unit
- Study start
- 18 Nov 2016 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 2 Mar 2016 (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.
Primary Objective
- To characterize the potential pharmacokinetic interactions of artemether -lumefantrine, amodiaquine and primaquine in healthy adult subjects.
Secondary Objectives
- To characterize the pharmacokinetic properties of artemether-lumefantrine, amodiaquine and primaquine when given alone and in combination.
- To evaluate the safety and tolerability of co-administered artemether-lumefantrine, amodiaquine and primaquine.
- To investigate pharmacogenetic polymorphisms affecting drug levels of artemether-lumefantrine, amodiaquine and primaquine and their metabolites.
Detailed description
The study design is an open-label pharmacokinetic study in healthy G6PD normal Thai subjects. This study will enroll 16 healthy subjects. Participants who pass the screening process will have 6 admissions in the hospital to receive 6 drug regimens as below
First admission visit: The subject may be randomized to receive either Artemether-Lumefantrine or Amodiaquine with more than 6 weeks washout period before second admission visit.
Second admission visit: Subject who receives Artemether-Lumefantrine from previous visit will receive amodiaquine in this visit and vice versa. This visit will required more than 6 weeks washout period before third admission visit.
Third admission visit: Every subject will receive Artemether-lumefantrine and Amodiaquine with more than 6 weeks washout period before forth admission visit.
Forth admission visit: Every subject will receive Primaquine with more than 1 week washout period before fifth admission visit.
Fifth admission visit: Subject may randomize to receive either Artemether-Lumefantrine and Primaquine or Artemether-Lumefantrine and Amodiaquine and Primaquine in this visit with more than 6 weeks washout period before sixth admission visit.
Sixth admission visit: Subject who receives Artemether-Lumefantrine and Amodiaquine and primaquine from previous visit will receive Artemether-Lumefantrine and Primaquine in this visit and vice versa.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Artemether-lumefantrine, Drug: Amodiaquine, Drug: Artemether-lumefantrine + Amodiaquine, Drug: Primaquine, Drug: Artemether-lumefantrine + Primaquine, Drug: Artemether-lumefantrine + Amodiaquine + Primaquine |
| Group B | Experimental | Drug: Amodiaquine, Drug: Artemether-lumefantrine, Drug: Artemether-lumefantrine + Amodiaquine, Drug: Primaquine, Drug: Artemether-lumefantrine + Amodiaquine + Primaquine, Drug: Artemether-lumefantrine + Primaquine |
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 or female non-smoker 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 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.
- 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 cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes (heart failure, hypokalemia) or with a family history of sudden cardiac death.
- A creatinine clearance <70 mL/min as determined by Cockcroft-Gault equation:
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 |
|---|---|---|
| Artemether-lumefantrineArtemether-lumefantrine on Day 0, 1 and 2 Washout period: more than 6 weeks | Drug | Group A |
| AmodiaquineAmodiaquine on Day 0, 1 and 2 Washout period: more than 6 weeks | Drug | Group A, Group B |
| Artemether-lumefantrineArtemether-lumefantrine on Day 0, 1 and 2 Washout period: more than 6 weeks | Drug | Group B |
| Artemether-lumefantrine + AmodiaquineArtemether-lumefantrine + Amodiaquine on Day 0, 1 and 2 Washout period: more than 6 weeks | Drug | Group A, Group B |
| PrimaquinePrimaquine on Day 0 Washout period: more than 1 week | Drug | Group A, Group B |
| Artemether-lumefantrine + PrimaquineArtemether-lumefantrine on Day 0, 1 and 2 + Primaquine on Day 0 Washout period: more than 6 weeks | Drug | Group A |
| Artemether-lumefantrine + Amodiaquine + PrimaquineArtemether-lumefantrine Day 0, 1 and 2 + Amodiaquine on Day 0, 1 and 2 + Primaquine on Day 0 Washout period: more than 6 weeks | Drug | Group A, Group B |
| Artemether-lumefantrine + PrimaquineArtemether-lumefantrine on Day 0, 1 and 2 + Primaquine on Day 0 | Drug | Group B |
Primary outcome
Area under the concentration-time curve (AUC (0-∞)
Time frame: 1 year
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Area under the concentration-time curve AUC (0-last)
Time frame: 1 year
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
Maximal concentration (Cmax)
Time frame: 1 year
for artemether, lumefantrine, amodiaquine and primaquine and their metabolites when given alone and in combination.
8 secondary outcomes
Elimination clearance (CL/F)
Time frame: 1 year
Terminal elimination half-life (t1/2)
Time frame: 1 year
Apparent volume of distribution (Vd)
Time frame: 1 year
Number of adverse events
Time frame: 1 year
Number of event concerning of abnormal electrocardiographic
Time frame: 1 year
Number of event concerning of abnormal vital signs
Time frame: 1 year
Number of event concerning of abnormal laboratory values
Time frame: 1 year
Identify polymorphisms of cytochrome 450
Time frame: 1 year
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2019.
- Individual participant dataSharing planned: Yes
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Healthy Participants
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Artemether-lumefantrine, Amodiaquine and Artemether-lumefantrine + Amodiaquine in people with Pharmacokinetic and Drug Combination, 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: stopped early, as of the sponsor's last update on 28 Jun 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 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early. Results are not available in the source record.
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?
Area under the concentration-time curve (AUC (0-∞) (time frame: 1 year). The study lists 3 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 28 Jun 2019.