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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003168-11 | EudraCT Number | ||
| C17030 | Other Identifier | Richmond Pharmacology Ltd |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Drug: XEN1101 XPF-008 Formulation Oral | Experimental | 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 |
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| Placebo - Microcrystalline cellulose oral | Placebo Comparator | 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 |
|
| Drug: XEN1101 XPF-008 Formulation Oral Drug: XEN1101 XPF-010 Formulation Oral | Experimental | 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 |
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| Drug: XEN1101 XPF-010 Formulation Oral | Experimental | XEN1101 XPF-010 Formulation Oral Part 4 will explore multiple dose PK |
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| Drug: XEN1101 XPF-010 Formulation Oral Drug: Itraconazole 400mg Oral | Experimental | 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) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XPF-008 | Drug | Capsule filled with XEN1101 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 & 2: Number of Participants with Adverse Events (AEs) | To assess AEs as a criteria of safety and tolerability | From screening (28 days prior to Day 1) through to 30 days post-final dose |
| Parts 1 & 2: Resting electrocardiogram (ECG) | 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 | 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 | 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 | 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 | To evaluate the safety and tolerability of XEN1101 (XPF-010) | At screening (27 days prior to Day -1) through to 31 days post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 & 2: Maximum Observed Plasma Concentration (Cmax) | 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) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gregory N Beatch, PhD | Xenon Pharmaceuticals Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Richmond Pharmacology Ltd. | London | SE1 1YR | United Kingdom |
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| ID | Term |
|---|---|
| C109691 | microcrystalline cellulose |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Microcrystalline Cellulose |
| Drug |
Placebo capsule |
|
| XPF-010 | Drug | Capsule filled with XEN1101 |
|
| Itraconazole 400mg | Drug | Oral |
|
| Part 3b: Maximum Observed Plasma Concentration (Cmax) of XEN1101 | 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 | 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 | 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 | 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 | 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 | 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 | To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole | Day 10 and Day 11 |
| Part 5: Area under the plasma concentration-time curve (AUC) of XEN1101 | To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole | Day 10 and Day 11 |
| Part 5: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations | To evaluate the safety and tolerability of XEN1101 (XPF-010) | At screening (27 days prior to Day -1) through to 51 days post dose |
Tmax is the time in hours to reach Cmax following dosing
| Day 1 predose through to 7 days post-final dose |
| Parts 1 & 2: Terminal elimination half-life (t1/2) | 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 |
| Parts 1 & 2: Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC0-last) | 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 |
| Parts 3 to 5: Cardiac Safety | 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. | 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 |
| D010879 |
| Piperazines |