A Phase I, blinded, randomized, single-centre, parallel-group, single-dose, dose-escalation, placebo-controlled study of the safety, tolerability, and pharmacokinetics of DNDI-6148 after oral dosing in healthy male subjects
Treatment of visceral and/or cutaneous leishmaniasis
Sixty-four (64) healthy male volunteers, aged 18 to 50 will be included in the study. Randomization is performed by block of 2 (1:1 for placebo:active) for the sentinel group, followed by block of 6 (1:5) for the main group of each dose cohort. A coding list was issued at the start of the trial, only available to unblinded personnel. Each cohort will include 8 participants (randomized in 6 active/2 placebo). A single dose of treatment will be administered as an oral suspension with increasing doses for each cohort of 8, such as 10 mg, 20 mg, 40 mg, 80 mg, 160 mg, 260 mg, 380 mg and 500 mg. The treatment will be administered as a single dose on Day 1. Last follow up visit is 72 h post-dosing.
1. Healthy Caucasian male volunteer aged 18 to 50 years inclusive 2. Non-smoker or light smoker of not more than 5 cigarettes a day. No smoking (or use of smoking substitute e.g. nicotine patch) is permitted from screening throughout the study 3. Body Mass Index (BMI) between 18 and 30.1 kg/m2 inclusive at screening 4. Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical and neurological examination) 5. Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position: 5.1. 95 mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg 5.2. 50 mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg 5.3. 45 bpm ≤ HR ≤ 90 bpm 5.4. Or considered NCS by investigators 6. Normal ECG recording on a 12-lead ECG at the screening visit: 6.1. 120 ms < PR < 210 ms 6.2. QRS < 120 ms 6.3. QTcf ≤ 430 ms for male 6.4. No sign of any relevant trouble of sinusal automatism 6.5. Or considered as non-clinically significant by investigators 7. Laboratory parameters within the normal range of the laboratory (hematological, hormonology, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged non-clinically significant by the Investigator; for example, isolated elevated bilirubin is acceptable if judged by the physician without clinical relevance (i.e. Gilbert's syndrome) 8. ALAT, ASAT and Creatinine values strictly within the normal range 9. A negative result for diagnostic test of SARS-CoV-2 at D-1 10. Normal dietary habits 11. Provision of written informed consent to participate as shown by a signature on the volunteer consent form, after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate 12. Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study 13. Covered by Health Insurance System and/or in compliance with th
1. Having previously received DNDI‐6148, or who participated in another clinical trial within 3 months prior and during the study, or 5‐times the half‐life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial) 2. Any history (direct questioning) or presence (physical examination) of cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic or infectious acute or chronic disease; including known or suspected HIV, HBV or HCV infection 3. With any clinically significant abnormality following review of pre‐study laboratory tests, vital signs, full physical examination and ECG 4. Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position 5. Who have a history of allergy, intolerance or photosensitivity to any drug 6. Who have a history of serious allergy, asthma, allergic skin rash or sensitivity to any drug 7. Who have a history of additional risk factors for “Torsades de Pointe” (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) 8. Current suicide risk or history of suicide risk (CSSRS baseline: “yes” answer to items 4 and/or 5); participants with a “yes” answer for current suicide risk should be referred for psychiatric evaluation 9. Participants with rare hereditary problems of fructose intolerance, glucose‐galactose malabsorption or sucrase‐isomaltase insufficiency 10. Who used a prescription medicine during the 28 days before the first dose of trial medication or use of an over‐the‐counter medicine (including antacid drug, with the exception of acetaminophen (paracetamol)), during the 7 days before the first dose of trial medication 11. History or presence of drug or alcohol abuse (more than 14 units of alcohol