Procedures
malaria, acoziborole
MALARIA, ADVERSE EVENT, ADVERSE EVENTS
Oral acoziborole was administered as a single 960 mg dose (3 × 320 mg tablets) to fasted patients (for at least 2 h before dosing). The study started with a pretreatment period of up to 15 days with baseline assessments, malaria testing, antimalarials (as needed), and anthelmintics given at least 3 days before acoziborole. Patients were observed in hospital until day 15 after treatment administration then for 18 months as outpatients with visits at approximately 3, 6, 12, and 18 months. During hospital admission, signs and symptoms of HAT were evaluated; neurological and physical examinations were performed; vital signs were recorded; and blood samples for haematology (haemoglobin, complete WBC count, and platelets), biochemistry (albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, chloride, creatinine, glucose, potassium, sodium, calcium, total bilirubin, bicarbonate, and total protein), and thyroid function were taken at baseline, day 5 and 11, and at each follow-up visit. Electrocardiograms (ECGs) and blood sampling for pharmacokinetic analysis were performed at baseline and at 4, 9, 24, 48, 72, 96, and 240 h after dosing. A concentration–response analysis was performed to assess the relationship between pharmacokinetics and QT interval with Fredericia (QTcFri) of acoziborole in patients with valid ECG that matched pharmacokinetic sampling. Pregnancy tests were done at baseline, day 11, and at each visit. Adverse events and concomitant medications were recorded during hospital stay until 6 months and serious adverse events were monitored until 18 months. Assessments including blood, lymph, and CSF sampling for the detection of trypanosomes and CSF WBC count (lumbar puncture) were performed at baseline, day 11, and follow-up visits (6, 12, and 18 months; 