| Eligibility |
Inclusion Criteria:
- Healthy males (Cohorts 1 to 7) or healthy WONCBP (Cohort 8)
- 18 to 55 years (Cohorts 1 to 7) or 18 to 60 years (Cohort 8)of age at the time of
signing informed consent
- Body mass index (BMI) of 18.0 to 30.1 kg/m2 as measured at screening
- General good physical health determined by medical and surgical history, physical
examination, 12-lead ECG, vital signs and clinical laboratory tests
- 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
- A resting Heart Rate (HR) between =40 and =90 bpm measured after 10 min rest in supine
position at screening, admission and pre-dose
- ECG recording without clinically significant abnormality, including QTcF measure of
=450 msec (male) or =470 msec (female) at screening, admission and pre-dose
- Having had no febrile seizures or infectious illness for at least 7 days prior to
administration of the Investigational Medicinal Product (IMP)
- Must be willing and able to communicate and participate in the whole study
- Must provide written informed consent
- Must agree to adhere to the contraception requirements and life-style restrictions
defined in the protocol
Exclusion Criteria:
- Subjects who have received any IMP in a clinical research study within the 3 months or
90 days prior to Day 1
- Subjects who are study site employees, or immediate family members of a study site or
sponsor employee
- Subjects who have previously been enrolled in this study and/or have received
DNDI-0690 previously
- History of any drug or alcohol abuse in the past 2 years
- Demonstrating excess in caffeine/xanthine consumption (more than 6 cups of coffee or
equivalent a day)
- 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
- 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
- Current users of e-cigarettes and nicotine replacement products and those who have
used these products within the last 12 months
- 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)
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as
assessed by the investigator or delegate at screening
- Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis
(especially aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma
glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), creatinine, and blood urea
nitrogen (BUN)) as judged by the investigator (laboratory parameters are listed in
Appendix 1). Subjects with Gilbert's syndrome are allowed
- Confirmed positive drugs of abuse test result
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or
human immunodeficiency virus (HIV) results
- Evidence of renal impairment at screening or admission, as indicated by an estimated
creatinine clearance (CLcr) of <80 mL/min using the Cockcroft-Gault equation
- History of clinically significant cardiovascular, renal, hepatic, neurological
(especially seizures), immunological, psychiatric, myopathies, bleeding tendency,
respiratory and particularly gastrointestinal (GI) disease, especially peptic
ulceration and chronic gastritis, GI bleeding, ulcerative colitis, Crohn's Disease or
Irritable Bowel Syndrome, as judged by the investigator
- History of additional risk factors for Torsades des Pointe (eg heart failure,
hypokalaemia, family history of long QT syndrome)
- Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or
sucrose-isomaltase insufficiency
- Any relevant GI complaints within 7 days of dosing
- Subjects with a history of cholecystectomy or gall stones (Cohort 7 only)
- 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)
- Presence or history of clinically significant allergy requiring treatment (including
asthma, urticaria, clinically significant allergic rash or other severe allergic
diathesis), as judged by the investigator. Hay fever is allowed unless it is active
- Donation or loss of greater than 500 mL of blood within the previous 3 months or more
than 100 mL within 30 days before signing Informed Consent Form (ICF) to this trial
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug
(including anti-acid drugs) or vitamins/herbal remedies (eg St. John's Wort and others
which are known to interfere with the Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein
(P-gp) metabolic pathways) or HRT in the 21 days before IMP administration.
Administration of up to 4 g of paracetamol per day within 7 days of IMP administration
is allowed
- Surgery within 12 weeks prior to screening, with the exception of appendectomy
- Any surgery (eg gastric bypass) or medical condition that may affect absorption of
orally administered drugs
- Failure to satisfy the investigator of fitness to participate for any other reason
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