Clinical trial NCT04727138: 3-part Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EXS21546
Official title: 3-part Study to Assess Safety, Tolerability, PK and PD of Single and Multiple Ascending Doses of EXS21546, and to Evaluate the Relative Bioavailability of 2 Formulations, in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Oncology
Lead sponsor: Exscientia AI Limited
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2021-01-27
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment emergent Adverse Events
timeFrame: 1 month
measure: EXS21546 and Metabolite Area under the plasma concentration versus time curve (AUC)
timeFrame: 17 days
measure: EXS21546 and Metabolite Peak Plasma Concentration (Cmax)
timeFrame: 17 days
Secondary outcomes:
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
Study officials:
affiliation: Quotient Sciences Principal Investigator
name: Phillip Evans
role: PRINCIPAL_INVESTIGATOR
References: