- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02605720
Cardiac Safety of Repeated Doses of Dihydroartemisinin-Piperaquine for the Use in Mass Treatment Campaigns (ECG-Lihir)
Electrocardiographic Safety Evaluation of Monthly Dihydroartemisinin-Piperaquine for the Use in Mass Treatment Campaigns to Block Malaria Transmission
Study Overview
Detailed Description
Given the absence of regulatory data related to the safety of repeated dosing, the European Medicines Agency has set a conservatively long 2-month "wash-out" period before administration of subsequent courses can be recommended. Unfortunately such a recommendation would make it impossible to implement effective mass drug administration with PPQ as this probably requires a maximum interval of one month between doses (in order to ensure that drug levels remain high enough to prevent infections occurring between doses). Therefore it is important that a formal evaluation is performed to regulatory standards that can conclusively document the safety of repeated monthly doses of PPQ. The extensive previous experience from monthly PPQ administration in China suggests that such a study would pose minimal risks to study participants.
Various studies have looked at the potential of DHA/PPQ to cause prolongation of corrected QT interval (QTc) intervals in humans. In a study of 62 adults and children, in Cambodia, electrocardiographic (ECG) findings after DHA/PPQ treatment showed a lengthening of the mean QTc by 11 ms. In two randomized controlled trials in Thailand, the mean QTc prolongation of 56 patients was 14 ms after the last dose of DHA/PPQ. The degree of QT prolongation observed in these studies was therefore similar to that seen with other anti-malarial drugs (including lumefantrine, and chloroquine) generally considered to have no cardiotoxicity in conventional dosing, and substantially less than with others such as halofantrine.and quinidine that have been associated with cardiotoxicity. Study-DM09-006 compared QTc data of healthy subjects that received DHA/PPQ with respective placebo groups and found maximum mean QT Fridericia's correction (QTcF) prolongation of 45.2 ms if co-administered with high fat, and 21.0 ms if fasting (EMEA/H/C/119). Of total of 96 participants given DHA/PPQ in the three studies mentioned above, no subjects showed QTc > 500ms post-treatment or prolongations (after- vs pre-dose) >60ms.
The proposed project is a pharmacovigilance study for electrocardiographic safety evaluation of monthly DHA/PPQ (administered as a conventional 3-day course repeated monthly for 3 months). The investigators aim to assess the safety of the drug to be used monthly in mass treatment campaigns.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New ireland province
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Londolovit, New ireland province, Papua New Guinea
- Lihir Medical Centre
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female ≥3 years to ≤50 years
- Good general health by medical history physical examination, baseline electrocardiographs and laboratory tests.
- No clinically relevant abnormalities in blood pressure and heart rate
No clinically relevant abnormalities in 12-lead ECG results*
*Patients with a QTcB or QTcF greater than 450 ms or clinically significant abnormalities of rhythm at Screening are not eligible. Patients with a pre-dose baseline value > 450 ms should be withdrawn from the study prior to dosing.
Exclusion Criteria:
- A history of additional risk factors for Torsades-des-Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
- The use of concomitant medications that prolong the QT/QTc interval;
- Any condition requiring regular concomitant medication, including herbal products and over-the-counter (OTC) medication or predicted need of any concomitant medication during the study;
- History of relevant clinical allergic reactions of any origin;
- Any other condition that in the opinion of the Investigator would interfere with the evaluation of the results or constitute a health risk for the subject;
- Patients who are not willing to give informed consent (patient and/or parent/legal representative), or who withdraw consent.
- Pregnant women in the 1st trimester of pregnancy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dihydroartemisinin-piperaquine
|
DHA/PPQ dose 2.1/17.1 mg/Kg daily for 3 days (PNG National Malaria Treatment Protocol) monthly for 3 months
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in QTcF interval (Fridericia's correction QT interval) after study drugs administration compared to baseline
Time Frame: Day 58
|
Day 58
|
Plasma piperaquine concentrations after study drugs
Time Frame: Day 58
|
Day 58
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in QTcF interval after study drugs administration compared to baseline
Time Frame: Day 3
|
Day 3
|
Change in QTcF interval after study drugs administration compared to baseline
Time Frame: Day 31
|
Day 31
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LihirMC
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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