Oncology
Conditions
Brief summary
A 3-part Study to Assess Safety, Tolerability, PK and PD of Single (Part 1) and Multiple (Part 2) Ascending Doses of EXS21546, and to Evaluate the Relative Bioavailability of a Solid Dose Formulation Compared to a Powder for Oral Suspension (Part 3), in Healthy Male Subjects.
Detailed description
Part 1 is a randomised, double-blind, placebo-controlled, SAD study with a food effect assessment. Part 2 is a randomised, double-blind, placebo controlled, MAD study over 14 days. In order to explore the potential CYP3A4 inducer effect, midazolam will also be administered in one cohort. Part 3 is a 3-period, open label, randomised, sequential study. Each subject will receive solid dose formulation and powder for oral suspension in a randomised manner.
Interventions
DRUGEXS21546 Powder for Oral Suspension
EXS21546 Powder for Oral Suspension
DRUGEXS21546 Granule in Capsule
EXS21546 Granule in Capsule
OTHERMidazolam
Interaction
OTHERFood Effect
Fed/Fasted
OTHERPlacebo Powder for Oral Suspension
Placebo Powder for Oral Suspension
Sponsors
Quotient Sciences
Exscientia AI Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1 and Part 2 are double blind. Part 3 is open label.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 18.0 to 30.0 kg/m2 * Weight ≥60 kg * Must adhere to contraception requirements
Exclusion criteria
* Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1 * Subjects who have previously been administered IMP in this study. * Evidence of current SARS-CoV-2 infection * History of any drug or alcohol abuse in the past 2 years * Regular alcohol consumption in males \>21 units per week * A confirmed positive alcohol breath test at screening or admission * Current smokers and those who have smoked within the last 12 months. A confirmed 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 * Subjects with pregnant or lactating partners * Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results * Regimen L only: History of sleep apnea * Subjects with a history of cholecystectomy or gall stones * Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients * Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active * Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment emergent Adverse Events | 1 month | Number of participants with treatment emergent Adverse Events |
| EXS21546 and Metabolite Area under the plasma concentration versus time curve (AUC) | 17 days | EXS21546 and Metabolite Area under the plasma concentration versus time curve (AUC) |
| EXS21546 and Metabolite Peak Plasma Concentration (Cmax) | 17 days | EXS21546 and Metabolite Peak Plasma Concentration (Cmax) |
Countries
United Kingdom
Outcome results
None listed