- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03340220
Safety, Tolerability, and Pharmacokinetics (PK) of Single and Multiple Ascending Oral Doses of XEN1101.
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
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London, United Kingdom, SE1 1YR
- Richmond Pharmacology Ltd.
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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
|
Capsule filled with XEN1101
|
Placebo Comparator: 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 |
Placebo capsule
|
Experimental: 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 |
Capsule filled with XEN1101
|
Experimental: Drug: XEN1101 XPF-010 Formulation Oral
XEN1101 XPF-010 Formulation Oral Part 4 will explore multiple dose PK |
Capsule filled with XEN1101
|
Experimental: 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) |
Oral
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Parts 1 & 2: Number of Participants with Adverse Events (AEs)
Time Frame: From screening (28 days prior to Day 1) through to 30 days post-final dose
|
To assess AEs as a criteria of safety and tolerability
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From screening (28 days prior to Day 1) through to 30 days post-final dose
|
Parts 1 & 2: Resting electrocardiogram (ECG)
Time Frame: At screening (28 days prior to Day 1) through to 7 days post-final dose
|
To assess ECG as a criteria of safety and tolerability
|
At screening (28 days prior to Day 1) through to 7 days post-final dose
|
Parts 1 & 2: Vital signs
Time Frame: At screening (28 days prior to Day 1) through to 7 days post-final dose
|
To assess vital signs as a criteria of safety and tolerability
|
At screening (28 days prior to Day 1) through to 7 days post-final dose
|
Part 3a: Maximum Observed Plasma Concentration (Cmax) of XEN1101
Time Frame: At screening (27 days prior to Day -1) through to 31 days post dose
|
To characterize the PK profile of XEN1101 and M11 (a metabolite of XEN1101) in plasma of single ascending, oral doses of XPF-010
|
At screening (27 days prior to Day -1) through to 31 days post dose
|
Part 3a: Area under the plasma concentration-time curve (AUC) of XEN1101
Time Frame: At screening (27 days prior to Day -1) through to 31 days post dose
|
To characterize the PK profile of XEN1101 and M11 (a metabolite of XEN1101) in plasma of single ascending, oral doses of XPF-010
|
At screening (27 days prior to Day -1) through to 31 days post dose
|
Part 3a: Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations
Time Frame: At screening (27 days prior to Day -1) through to 31 days post dose
|
To evaluate the safety and tolerability of XEN1101 (XPF-010)
|
At screening (27 days prior to Day -1) through to 31 days post dose
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Part 3b: Maximum Observed Plasma Concentration (Cmax) of XEN1101
Time Frame: At screening (27 days prior to Day -1) through to 31 days post dose
|
To assess the Food Effect on PK (Cmax) and the relative bioavailability/comparability (Cmax) of XEN1101 following single oral doses of XPF-010 (fed), XPF-008 (fed) and XPF-010 (fasted)
|
At screening (27 days prior to Day -1) through to 31 days post dose
|
Part 3b: Area under the plasma concentration-time curve (AUC) of XEN1101
Time Frame: At screening (27 days prior to Day -1) through to 31 days post dose
|
To assess the Food Effect on PK (AUC0-240h) and the relative bioavailability/comparability (AUC0-240h) of XEN1101 following single oral doses of XPF-010 (fed), XPF-008 (fed) and XPF-010 (fasted)
|
At screening (27 days prior to Day -1) through to 31 days post dose
|
Part 3b: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
Time Frame: At screening (27 days prior to Day -1) through to 31 days post dose
|
To evaluate the safety and tolerability of XEN1101
|
At screening (27 days prior to Day -1) through to 31 days post dose
|
Part 4: Maximum Observed Plasma Concentration (Cmax) of XEN1101
Time Frame: At screening (27 days prior to Day -1) through to 51 days post dose
|
To characterize the PK profile of XEN1101 and M11 (metabolite of XEN1101) in plasma of multiple daily oral doses of XPF-010
|
At screening (27 days prior to Day -1) through to 51 days post dose
|
Part 4: Area under the plasma concentration-time curve (AUC) of XEN1101
Time Frame: At screening (27 days prior to Day -1) through to 51 days post dose
|
To characterize the PK profile of XEN1101 and M11 (metabolite of XEN1101) in plasma of multiple daily oral doses of XPF-010
|
At screening (27 days prior to Day -1) through to 51 days post dose
|
Part 4: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
Time Frame: At screening (27 days prior to Day -1) through to 51 days post dose
|
To evaluate the safety and tolerability of XEN1101 (XPF-010)
|
At screening (27 days prior to Day -1) through to 51 days post dose
|
Part 5: Maximum Observed Plasma Concentration (Cmax) of XEN1101
Time Frame: Day 10 and Day 11
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To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole
|
Day 10 and Day 11
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Part 5: Area under the plasma concentration-time curve (AUC) of XEN1101
Time Frame: Day 10 and Day 11
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To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole
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Day 10 and Day 11
|
Part 5: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
Time Frame: At screening (27 days prior to Day -1) through to 51 days post dose
|
To evaluate the safety and tolerability of XEN1101 (XPF-010)
|
At screening (27 days prior to Day -1) through to 51 days post dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Parts 1 & 2: Maximum Observed Plasma Concentration (Cmax)
Time Frame: Day 1 predose through to 7 days post-final dose
|
Cmax is the maximum observed plasma concentration in ng/mL
|
Day 1 predose through to 7 days post-final dose
|
Parts 1 & 2: Time to the Maximum Observed Plasma Concentration (Tmax)
Time Frame: Day 1 predose through to 7 days post-final dose
|
Tmax is the time in hours to reach Cmax following dosing
|
Day 1 predose through to 7 days post-final dose
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Parts 1 & 2: Terminal elimination half-life (t1/2)
Time Frame: Day 1 predose through to 7 days post-final dose
|
The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase
|
Day 1 predose through to 7 days post-final dose
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Parts 1 & 2: Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC0-last)
Time Frame: Day 1 predose through to 7 days post-final dose
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The area under the plasma concentration-time curve [in ng.h/mL] from time zero to the time corresponding to the last quantifiable plasma concentration
|
Day 1 predose through to 7 days post-final dose
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Parts 3 to 5: Cardiac Safety
Time Frame: 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
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To evaluate the cardiovascular safety profile of XEN1101 (XPF-010), assessing potential ECG interval changes from baseline following dosing, in particular any effects on the QTc interval.
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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
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Gregory N Beatch, PhD, Xenon Pharmaceuticals Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Itraconazole
Other Study ID Numbers
- XPF-008-101a
- 2017-003168-11 (EudraCT Number)
- C17030 (Other Identifier: Richmond Pharmacology Ltd)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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