Cardiac Safety of Repeated Doses of Dihydroartemisinin-Piperaquine for the Use in Mass Treatment Campaigns (ECG-Lihir)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02605720|
Recruitment Status : Completed
First Posted : November 16, 2015
Last Update Posted : March 3, 2016
|Condition or disease||Intervention/treatment||Phase|
|Malaria||Drug: Dihydroartemisinin-piperaquine||Phase 3|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||78 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Electrocardiographic Safety Evaluation of Monthly Dihydroartemisinin-Piperaquine for the Use in Mass Treatment Campaigns to Block Malaria Transmission|
|Study Start Date :||September 2015|
|Actual Primary Completion Date :||January 2016|
|Actual Study Completion Date :||February 2016|
DHA/PPQ dose 2.1/17.1 mg/Kg daily for 3 days (PNG National Malaria Treatment Protocol) monthly for 3 months
Other Name: Eurartesim
- Change in QTcF interval (Fridericia's correction QT interval) after study drugs administration compared to baseline [ Time Frame: Day 58 ]
- Plasma piperaquine concentrations after study drugs [ Time Frame: Day 58 ]
- Change in QTcF interval after study drugs administration compared to baseline [ Time Frame: Day 3 ]
- Change in QTcF interval after study drugs administration compared to baseline [ Time Frame: Day 31 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02605720
|Papua New Guinea|
|Lihir medical Centre|
|Londolovit, New ireland province, Papua New Guinea|