3-part Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EXS21546

Exscientia

Status and phase: Completed; Phase 1

Conditions: Oncology

Treatments: Drug: EXS21546 Granule in Capsule; Other: Placebo Powder for Oral Suspension; Other: Food Effect; Drug: EXS21546 Powder for Oral Suspension; Other: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT04727138

EXS21546-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 64 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

64 participants in 3 patient groups, including a placebo group

EXS21546 Powder for Oral Suspension

Experimental group

Description:

EXS21546 Powder for Oral Suspension

Treatment:

Drug: EXS21546 Powder for Oral Suspension

Other: Food Effect

Other: Midazolam

Placebo

Placebo Comparator group

Description:

Placebo Powder for Oral Suspension

Treatment:

Other: Placebo Powder for Oral Suspension

Other: Food Effect

Other: Midazolam

EXS21546 Granule in Capsule

Experimental group

Description:

EXS21546 Granule in Capsule

Treatment:

Drug: EXS21546 Granule in Capsule

Other: Food Effect