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

Phase 1

Completed

• Conditions: Oncology
• Interventions: Drug: EXS21546 Granule in Capsule; Drug: EXS21546 Powder for Oral Suspension; Other: Midazolam; Other: Food Effect; Other: Placebo Powder for Oral Suspension

• Registration Number: NCT04727138
• Lead Sponsor: Exscientia AI Limited

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.

Study Timeline

• Study Start: 2020-12-08
• Study First Submitted: 2020-12-23
• Study First Submitted QC: 2021-01-26
• Study First Posted: 2021-01-27
• Primary Completion: 2022-04-16
• Status Verified: 2022-05
• Study Completion: 2022-05-12
• Last Update Submitted: 2022-05-12
• Last Update Posted: 2022-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
EXS21546 Powder for Oral Suspension	Midazolam	EXS21546 Powder for Oral Suspension
Placebo	Midazolam	Placebo Powder for Oral Suspension
EXS21546 Granule in Capsule	Food Effect	EXS21546 Granule in Capsule
EXS21546 Powder for Oral Suspension	Food Effect	EXS21546 Powder for Oral Suspension
EXS21546 Granule in Capsule	EXS21546 Granule in Capsule	EXS21546 Granule in Capsule
EXS21546 Powder for Oral Suspension	EXS21546 Powder for Oral Suspension	EXS21546 Powder for Oral Suspension
Placebo	Placebo Powder for Oral Suspension	Placebo Powder for Oral Suspension
Placebo	Food Effect	Placebo Powder for Oral Suspension

Primary Outcome Measures

Name	Time	Method
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)
Number of participants with treatment emergent Adverse Events	1 month	Number of participants with treatment emergent Adverse Events

Trial Locations

Locations (1)

Quotient Sciences; 🇬🇧 Nottingham, United Kingdom