Clinical trial NCT03340220: Safety, Tolerability, and Pharmacokinetics (PK) of Single and Multiple Ascending Oral Doses of XEN1101.
Official title: Phase 1, First-in-human, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and PK of Single and Multiple Ascending Oral Doses of XEN1101 and Preliminary Open-label Pharmacodynamic Assessment in Healthy Subjects Addendum: Phase 1, Randomised, Multi Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Relative Bioavailability and Food Effect of Single and Multiple Ascending Doses of XEN1101 and Preliminary Drug-Drug Interaction Assessment With Itraconazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Xenon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-13
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Parts 1 & 2: Number of Participants with Adverse Events (AEs)
timeFrame: From screening (28 days prior to Day 1) through to 30 days post-final dose
measure: Parts 1 & 2: Resting electrocardiogram (ECG)
timeFrame: At screening (28 days prior to Day 1) through to 7 days post-final dose
measure: Parts 1 & 2: Vital signs
timeFrame: At screening (28 days prior to Day 1) through to 7 days post-final dose
measure: Part 3a: Maximum Observed Plasma Concentration (Cmax) of XEN1101
timeFrame: At screening (27 days prior to Day -1) through to 31 days post dose
measure: Part 3a: Area under the plasma concentration-time curve (AUC) of XEN1101
timeFrame: At screening (27 days prior to Day -1) through to 31 days post dose
measure: Part 3a: Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations
timeFrame: At screening (27 days prior to Day -1) through to 31 days post dose
measure: Part 3b: Maximum Observed Plasma Concentration (Cmax) of XEN1101
timeFrame: At screening (27 days prior to Day -1) through to 31 days post dose
measure: Part 3b: Area under the plasma concentration-time curve (AUC) of XEN1101
timeFrame: At screening (27 days prior to Day -1) through to 31 days post dose
measure: Part 3b: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
timeFrame: At screening (27 days prior to Day -1) through to 31 days post dose
measure: Part 4: Maximum Observed Plasma Concentration (Cmax) of XEN1101
timeFrame: At screening (27 days prior to Day -1) through to 51 days post dose
measure: Part 4: Area under the plasma concentration-time curve (AUC) of XEN1101
timeFrame: At screening (27 days prior to Day -1) through to 51 days post dose
measure: Part 4: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
timeFrame: At screening (27 days prior to Day -1) through to 51 days post dose
measure: Part 5: Maximum Observed Plasma Concentration (Cmax) of XEN1101
timeFrame: Day 10 and Day 11
measure: Part 5: Area under the plasma concentration-time curve (AUC) of XEN1101
timeFrame: Day 10 and Day 11
measure: Part 5: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
timeFrame: At screening (27 days prior to Day -1) through to 51 days post dose
Secondary outcomes:
measure: Parts 1 & 2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1 predose through to 7 days post-final dose
measure: Parts 1 & 2: Time to the Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 1 predose through to 7 days post-final dose
measure: Parts 1 & 2: Terminal elimination half-life (t1/2)
timeFrame: Day 1 predose through to 7 days post-final dose
measure: Parts 1 & 2: Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC0-last)
timeFrame: Day 1 predose through to 7 days post-final dose
measure: Parts 3 to 5: Cardiac Safety
timeFrame: At screening (27 days prior to Day -1) through to 11 days post dose for Parts 3a and 3b and at screening (27days prior to Day -1) through to Day 21
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Richmond Pharmacology Ltd.
Study officials:
affiliation: Xenon Pharmaceuticals Inc.
name: Gregory N Beatch, PhD
role: STUDY_DIRECTOR
References: