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

Xenon Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Itraconazole 400mg; Drug: XPF-008; Drug: Microcrystalline Cellulose; Drug: XPF-010

Study type: Interventional

Funder types: Industry

Identifiers

NCT03340220

C17030 (Other Identifier)

XPF-008-101a

2017-003168-11 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key 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)

Key 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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130 participants in 5 patient groups, including a placebo group

Drug: XEN1101 XPF-008 Formulation Oral

Experimental group

Description:

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

Treatment:

Drug: XPF-008

Placebo - Microcrystalline cellulose oral

Placebo Comparator group

Description:

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

Treatment:

Drug: Microcrystalline Cellulose

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

Experimental group

Description:

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

Treatment:

Drug: XPF-010

Drug: XEN1101 XPF-010 Formulation Oral

Experimental group

Description:

XEN1101 XPF-010 Formulation Oral Part 4 will explore multiple dose PK

Treatment:

Drug: XPF-010

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

Experimental group

Description:

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)

Treatment:

Drug: Itraconazole 400mg