Table 4 Major amendments
Amendment version | Basis/rationale of amendment | Amendment |
|---|---|---|
Amendment 1 | The information provided by the ASAQ manufacturer of some transitory increase of ALAT at day 28 post-treatment. | ALAT measurement at day 28 was introduced |
Amendment 2 | The reproductive toxicity of DHAPQ and mefloquine was made available by the manufacturer and showed in the animal model prolonged length of gestation and dystocic pup expulsion in animals treated close to delivery. | Modification of the original inclusion criterion of gestation ≥16 weeks to gestation ≥16 weeks and <37 weeks |
Amendment 3 | paragraph on placenta biopsy is added to the ICF (was omitted by mistake in the previous versions) | |
Amendment 4 | Amendment was done on the basis of the modification of blood piperaquine concentrations by food intake which could result in a QTc prolongation, a risk factor for serious cardiac arrhythmia. | • DHA/PQP tablets should be administered with water only and at least 3 hours apart from meal, mainly for the second and third administration. |
• correction of dosage of DHA/PQP, should be 3 tablets for 3 consecutive days instead of 2 tablets for 3 consecutive days as erroneously stated in the previous versions of the protocol. | ||
• notification of change in sites in Malawi. | ||
• % of SDV reduced to 10% | ||
Amendment 5 | Need for baseline drug plasma concentrations | PK sample at day 0 before study drug administration for the patients participating in the population PK study |
Amendment 6 | one additional site |