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OpenTrials
Completed

NCT Number: NCT03340220

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

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.

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Key information

Conditions

Healthy Volunteers

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Richmond Pharmacology Ltd.

London, SE1 1YR, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

XPF-008

Drug

Capsule filled with XEN1101

Microcrystalline Cellulose

Drug

Placebo capsule

XPF-010

Drug

Capsule filled with XEN1101

Itraconazole 400mg

Drug

Oral

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. 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)

  8. 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)

  9. 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

  10. 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

  11. 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

  12. 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)

  13. Part 5: Maximum Observed Plasma Concentration (Cmax) of XEN1101

    Time frame: Day 10 and Day 11

    To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole

  14. Part 5: Area under the plasma concentration-time curve (AUC) of XEN1101

    Time frame: Day 10 and Day 11

    To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole

  15. 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)

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

    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

  5. 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

    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.

Sponsors and collaborators

Lead sponsor

Xenon Pharmaceuticals Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Nov 13, 2017
Registry last updated
May 11, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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