Safety, Tolerability, and Pharmacokinetics (PK) of Single and Multiple Ascending Oral Doses of XEN1101.

NCT ID: NCT03340220

Last Updated: 2023-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-13
• Study Completion Date: 2021-11-26

Brief Summary

The XEN1101 Phase 1 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety, tolerability and PK of both single ascending doses (SAD) and multiple ascending doses (MAD) of XEN1101 in healthy subjects. In addition to safety and PK data, the clinical trial has been designed to include a pharmacodynamic read-out by incorporating a pilot transcranial magnetic stimulation (TMS) sub-study. The TMS model sub-study is designed to demonstrate delivery of XEN1101 into the central nervous system and to observe a change in cortical excitability as measured by EEG and/or electromyographic (EMG) activity.

Part 3, 4 and 5: Phase 1, randomised, multi part study to evaluate the safety, tolerability, PK, relative bioavailability and food effect of single and multiple ascending doses of XEN1101 and Preliminary Drug-Drug Interaction Assessment with Itraconazole.

Detailed Description

Part 1 will study safety, tolerability, PK of single ascending doses (SAD) of XPF-008 as well as the impact and variability of single ascending doses of XPF-008 on TMS.

Part 2 will study the safety, tolerability and PK of multiple ascending doses (MAD) of XPF-008

Part 3 will explore dose proportionality of XPF-010 and confirm dosing for subsequent cohorts, and the food effect and relative bioavailability of XPF-010 compared to XPF-008.

Part 4 will explore multiple dose PK.

Part 5 will explore the drug-drug interaction of XPF-010, when given with itraconazole.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Drug: XEN1101 XPF-008 Formulation Oral

XEN1101 XPF-008 Formulation Part 1 - Single ascending dose: Single oral dose for each cohort Part 2 - Multiple ascending dose: 7 days of single oral dose daily for each cohort

Group Type: EXPERIMENTAL

XPF-008

Intervention Type: DRUG

Capsule filled with XEN1101

Placebo - Microcrystalline cellulose oral

Part 1- Single Ascending Dose: Single oral dose for each cohort

Part 2 - Multiple Ascending Dose: 7 days of single oral dose daily for each cohort

Group Type: PLACEBO_COMPARATOR

Microcrystalline Cellulose

Intervention Type: DRUG

Placebo capsule

Drug: XEN1101 XPF-008 Formulation Oral Drug: XEN1101 XPF-010 Formulation Oral

XEN1101 XPF-008 and XPF-010 Formulation Cross Over

Part 3 will explore dose proportionality of XPF-010 and confirm dosing for subsequent cohorts, and the food effect and relative bioavailability of XPF-010 compared to XPF-008

Group Type: EXPERIMENTAL

XPF-010

Intervention Type: DRUG

Capsule filled with XEN1101

Drug: XEN1101 XPF-010 Formulation Oral

XEN1101 XPF-010 Formulation Oral

Part 4 will explore multiple dose PK

Group Type: EXPERIMENTAL

XPF-010

Intervention Type: DRUG

Capsule filled with XEN1101

Drug: XEN1101 XPF-010 Formulation Oral Drug: Itraconazole 400mg Oral

XEN1101 XPF-010 Formulation + Itraconazole

Part 5 will explore the drug-drug interaction of XPF-010, when given with itraconazole (400mg, single dose, oral solution, fasted)

Group Type: EXPERIMENTAL

Itraconazole 400mg

Intervention Type: DRUG

Oral

Interventions

XPF-008

Capsule filled with XEN1101

Intervention Type: DRUG

Microcrystalline Cellulose

Placebo capsule

Intervention Type: DRUG

XPF-010

Capsule filled with XEN1101

Intervention Type: DRUG

Itraconazole 400mg

Oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male or females aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.50 and 30.00 kg/m2
• Must agree to use effective methods of contraception, if applicable
• Able to swallow capsules
• Able to provide written, personally signed and dated informed consent form (ICF)

Exclusion Criteria

• Any history of epileptic seizures
• Any current and relevant history of significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk, affect clinical or laboratory results, or the subject's ability to participate in the study
• Answering "yes" to any of the questions within the Columbia Suicide Severity Rating Scale
• Mental incapacity or lingual barriers precluding adequate understanding, cooperation, and compliance with the study
• No prescription or over-the-counter (OTC) medications (except hormonal contraception), herbal or dietary supplements OTC medications 14 days prior to dosing to study end
• No smoking 60 days prior to dosing to study end
• No soft drugs 3 months prior to Screening and hard drugs 2 years prior to Screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Xenon Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory N Beatch, PhD

Role: STUDY_DIRECTOR

Xenon Pharmaceuticals Inc.

Locations

Richmond Pharmacology Ltd.

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

2017-003168-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C17030

Identifier Type: OTHER

Identifier Source: secondary_id

XPF-008-101a

Identifier Type: -

Identifier Source: org_study_id