Visceral leishmaniasis, cutaneous leishmaniasis Infections and Infestations
Conditions
Interventions
This is a single centre, double-blind, randomised, placebo-controlled, parallel-group, single oral dose, dose-escalation study in healthy male and women of non-childbearing potential (WONCBP) subjects
Sponsors
Drugs for Neglected Diseases Initiative
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy males (Cohorts 1 to 7) or healthy WONCBP (Cohort 8) 2. 18 to 55 years (Cohorts 1 to 7) or 18 to 60 years (Cohort 8) of age at the time of signing informed consent 3. Body mass index (BMI) of 18.0 to 30.1 kg/m² as measured at screening 4. General good physical health determined by medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory tests 5. Normal blood pressure: Systolic blood pressure between =90 and =140 mmHg, Diastolic blood pressure =90 mmHg, measured after 10 min rest in supine position at screening, admission and pre-dose 6. A resting HR between =40 and =90 bpm measured after 10 min rest in supine position at screening, admission and pre-dose 7. ECG recording without clinically significant abnormality, including QTcF measure of =450 msec (male) or =470 msec (female) at screening, admission and pre-dose 8. Having had no febrile seizures or infectious illness for at least 7 days prior to administration of the IMP (Day 1) 9. Must be willing and able to communicate and participate in the whole study 10. Must provide written informed consent 11. Must agree to adhere to the contraception requirements
Exclusion criteria
Exclusion criteria: 1. Subjects who have received any IMP in a clinical research study within the 3 months or 90 days prior to Day 1 2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee 3. Subjects who have previously been enrolled in this study and/or have received DNDI 0690 previously 4. History of any drug or alcohol abuse in the past 2 years 5. Demonstrating excess in caffeine/xanthine consumption (more than 6 cups of coffee or equivalent a day) 6. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type). As confirmed by a positive alcohol breath test at screening or admission 7. Current smokers and those who have smoked within the last 12 months. As confirmed by a breath carbon monoxide reading of greater than 10 ppm at screening or admission 8. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 9. Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral tubal ligation, bilateral tubal occlusion and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone [FSH] concentration =40 IU/L) 10. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 11. Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis (especially AST, ALT, gamma glutamyl transpeptidase [GGT], ALP, creatinine, and BUN) as judged by the investigator (laboratory parameters are listed in Appendix 1). Subjects with Gilbert’s syndrome are allowed 12. Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1) 13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results 14. Evidence of renal impairment at screening or admission, as indicated by an estimated CLcr of <80 mL/min using the Cockcroft-Gault equation 15. History of clinically significant cardiovascular, renal, hepatic, neurological (especially seizures), immunological, psychiatric, myopathies, bleeding tendency, respiratory and particularly GI disease, especially peptic ulceration and chronic gastritis, GI bleeding, ulcerative colitis, Crohn’s Disease or Irritable Bowel Syndrome, as judged by the investigator 16. History of additional risk factors for Torsades des Pointe (eg heart failure, hypokalaemia, family history of long QT syndrome) 17. Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency 18. Any relevant GI complaints within 7 days of dosing 19. Subjects with a history of cholecystectomy or gall stones (Cohort 7 only) 20. Serious adverse reaction or clinically relevant hypersensitivity to any drug or the formulation excipients (Hypromellose [HPMC], sodium lauryl sulphate [SLS], sucrose, croscarmellose sodium and magnesium stearate) 21. Presence or history of clinically significant allergy requiring treatment (including asthma, urticaria,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Treatment-emergent adverse events (TEAEs) from baseline up to 7-10 days post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured by blood test: 1. Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity (AUC0-inf) from pre-dose up to 72 hours post-dose 2. Observed Maximum Concentration (Cmax) from pre-dose up to 72 hours post-dose 3. Time to Maximum Observed Plasma Concentration (Tmax) from pre-dose up to 72 hours post-dose 4. Apparent elimination half-life (T1/2) from pre-dose up to 72 hours post-dose | — |
Countries
England, United Kingdom
Outcome results
None listed