Study of first dosing of a new compound DNDi-6148 in healthy volunteers to assess safety and drug levels in blood and urine after escalating single dose
- Conditions
- Treatment of visceral and/or cutaneous leishmaniasisInfections and InfestationsLeishmaniasis
- Registration Number
- ISRCTN54981564
- Lead Sponsor
- Drugs for Neglected Diseases Initiative
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 64
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 the recommendations of National Law in force relating to biomedical research
14. Must agree to adhere to the contraception requirements defined in Section 4.3: use of condom by the male volunteer plus an effective method of contraception for the volunteer or their partner of childbearing potential from study drug administration until 90 days post-dosing OR use of a condom for 10 days post-dosing if the partner is known to be pregnant
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 per week, one unit = 8 g or about 10 mL of pure alcohol)
12. Excessive consumption of beverages with xanthine bases (more than one liter/day)
13. Who drink more than 8 cups daily of beverage containing caffeine
14. Who has regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco
15. Who use dietary supplements or herbal remedies (such as St John’s Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathways during the 28 days before the first dose of trial medication
16. Grapefruit should also be avoided during the 7 days before the first dose of trial medication
17. Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV 1 or 2) tests
18. Positive results of screening for drugs of abuse (opiates, cocaine, amphetamine, cannabis, benzodiazepines)
19. Blood donation (including in the frame of a clinical trial) within 12 weeks before administration
20. General anaesthesia within 3 months before trial medication administration
21. Inability to abstain from intensive muscular effort
22. Who have any clinical condition or prior therapy which, in the opinion, of the Investigator, made the participant unsuitable for the study
23. Who had surgery (e.g. stomach bypass) or medical condition that might affect absorption of study drug taken orally
24. Who had febrile illness within 1 week before the start of the study
25. Participant who, in t
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method