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

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

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.

Study Overview

• Status: Completed
• Conditions: Oncology
• Intervention / Treatment: Drug: EXS21546 Powder for Oral Suspension; Other: Midazolam; Other: Food Effect; Other: Placebo Powder for Oral Suspension; Drug: EXS21546 Granule in Capsule

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 Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXS21546 Powder for Oral Suspension	Drug: EXS21546 Powder for Oral Suspension; EXS21546 Powder for Oral Suspension; Other: Midazolam; Interaction; Other: Food Effect; Fed/Fasted
Placebo Comparator: Placebo; Placebo Powder for Oral Suspension	Other: Midazolam; Interaction; Other: Food Effect; Fed/Fasted; Other: Placebo Powder for Oral Suspension; Placebo Powder for Oral Suspension
Experimental: EXS21546 Granule in Capsule	Other: Food Effect; Fed/Fasted; Drug: EXS21546 Granule in Capsule; EXS21546 Granule in Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment emergent Adverse Events	Number of participants with treatment emergent Adverse Events	1 month
EXS21546 and Metabolite Area under the plasma concentration versus time curve (AUC)	EXS21546 and Metabolite Area under the plasma concentration versus time curve (AUC)	17 days
EXS21546 and Metabolite Peak Plasma Concentration (Cmax)	EXS21546 and Metabolite Peak Plasma Concentration (Cmax)	17 days

Collaborators and Investigators

• Sponsor: Exscientia Limited
• Collaborators: Quotient Sciences
• Investigators: Principal Investigator: Phillip Evans, Quotient Sciences Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): April 16, 2022
• Study Completion (Actual): May 12, 2022

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: EXS21546-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No