Ignite Creation Date:
2025-12-25 @ 4:27 AM
Ignite Modification Date:
2026-03-06 @ 9:17 AM
Study NCT ID:
NCT03340220
Status:
COMPLETED
Last Update Posted:
2023-05-11
First Post:
2017-10-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety, Tolerability, and Pharmacokinetics (PK) of Single and Multiple Ascending Oral Doses of XEN1101.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C109691', 'term': 'microcrystalline cellulose'}, {'id': 'D017964', 'term': 'Itraconazole'}], 'ancestors': [{'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D010879', 'term': 'Piperazines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 130}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-11-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-05', 'completionDateStruct': {'date': '2021-11-26', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-05-08', 'studyFirstSubmitDate': '2017-10-31', 'studyFirstSubmitQcDate': '2017-11-07', 'lastUpdatePostDateStruct': {'date': '2023-05-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-11-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-11-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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', 'description': 'To assess AEs as a criteria of safety and tolerability'}, {'measure': 'Parts 1 & 2: Resting electrocardiogram (ECG)', 'timeFrame': 'At screening (28 days prior to Day 1) through to 7 days post-final dose', 'description': 'To assess ECG as a criteria of safety and tolerability'}, {'measure': 'Parts 1 & 2: Vital signs', 'timeFrame': 'At screening (28 days prior to Day 1) through to 7 days post-final dose', 'description': 'To assess vital signs as a criteria of safety and tolerability'}, {'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', 'description': 'To characterize the PK profile of XEN1101 and M11 (a metabolite of XEN1101) in plasma of single ascending, oral doses of XPF-010'}, {'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', 'description': 'To characterize the PK profile of XEN1101 and M11 (a metabolite of XEN1101) in plasma of single ascending, oral doses of XPF-010'}, {'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', 'description': 'To evaluate the safety and tolerability of XEN1101 (XPF-010)'}, {'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', 'description': '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)'}, {'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', 'description': '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)'}, {'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', 'description': 'To evaluate the safety and tolerability of XEN1101'}, {'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', 'description': 'To characterize the PK profile of XEN1101 and M11 (metabolite of XEN1101) in plasma of multiple daily oral doses of XPF-010'}, {'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', 'description': 'To characterize the PK profile of XEN1101 and M11 (metabolite of XEN1101) in plasma of multiple daily oral doses of XPF-010'}, {'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', 'description': 'To evaluate the safety and tolerability of XEN1101 (XPF-010)'}, {'measure': 'Part 5: Maximum Observed Plasma Concentration (Cmax) of XEN1101', 'timeFrame': 'Day 10 and Day 11', 'description': 'To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole'}, {'measure': 'Part 5: Area under the plasma concentration-time curve (AUC) of XEN1101', 'timeFrame': 'Day 10 and Day 11', 'description': 'To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole'}, {'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', 'description': 'To evaluate the safety and tolerability of XEN1101 (XPF-010)'}], 'secondaryOutcomes': [{'measure': 'Parts 1 & 2: Maximum Observed Plasma Concentration (Cmax)', 'timeFrame': 'Day 1 predose through to 7 days post-final dose', 'description': 'Cmax is the maximum observed plasma concentration in ng/mL'}, {'measure': 'Parts 1 & 2: Time to the Maximum Observed Plasma Concentration (Tmax)', 'timeFrame': 'Day 1 predose through to 7 days post-final dose', 'description': 'Tmax is the time in hours to reach Cmax following dosing'}, {'measure': 'Parts 1 & 2: Terminal elimination half-life (t1/2)', 'timeFrame': 'Day 1 predose through to 7 days post-final dose', 'description': 'The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase'}, {'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', 'description': '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'}, {'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', 'description': '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.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Healthy Volunteers']}, 'descriptionModule': {'briefSummary': '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.\n\nPart 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.', 'detailedDescription': '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.\n\nPart 2 will study the safety, tolerability and PK of multiple ascending doses (MAD) of XPF-008\n\nPart 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.\n\nPart 4 will explore multiple dose PK.\n\nPart 5 will explore the drug-drug interaction of XPF-010, when given with itraconazole.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Key Inclusion Criteria:\n\n* 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\n* Must agree to use effective methods of contraception, if applicable\n* Able to swallow capsules\n* Able to provide written, personally signed and dated informed consent form (ICF)\n\nKey Exclusion Criteria:\n\n* Any history of epileptic seizures\n* 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\n* Answering "yes" to any of the questions within the Columbia Suicide Severity Rating Scale\n* Mental incapacity or lingual barriers precluding adequate understanding, cooperation, and compliance with the study\n* 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\n* No smoking 60 days prior to dosing to study end\n* No soft drugs 3 months prior to Screening and hard drugs 2 years prior to Screening'}, 'identificationModule': {'nctId': 'NCT03340220', 'briefTitle': 'Safety, Tolerability, and Pharmacokinetics (PK) of Single and Multiple Ascending Oral Doses of XEN1101.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Xenon Pharmaceuticals Inc.'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'XPF-008-101a'}, 'secondaryIdInfos': [{'id': '2017-003168-11', 'type': 'EUDRACT_NUMBER'}, {'id': 'C17030', 'type': 'OTHER', 'domain': 'Richmond Pharmacology Ltd'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Drug: XEN1101 XPF-008 Formulation Oral', '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', 'interventionNames': ['Drug: XPF-008']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo - Microcrystalline cellulose oral', 'description': 'Part 1- Single Ascending Dose: Single oral dose for each cohort\n\nPart 2 - Multiple Ascending Dose: 7 days of single oral dose daily for each cohort', 'interventionNames': ['Drug: Microcrystalline Cellulose']}, {'type': 'EXPERIMENTAL', 'label': 'Drug: XEN1101 XPF-008 Formulation Oral Drug: XEN1101 XPF-010 Formulation Oral', 'description': 'XEN1101 XPF-008 and XPF-010 Formulation Cross Over\n\nPart 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', 'interventionNames': ['Drug: XPF-010']}, {'type': 'EXPERIMENTAL', 'label': 'Drug: XEN1101 XPF-010 Formulation Oral', 'description': 'XEN1101 XPF-010 Formulation Oral\n\nPart 4 will explore multiple dose PK', 'interventionNames': ['Drug: XPF-010']}, {'type': 'EXPERIMENTAL', 'label': 'Drug: XEN1101 XPF-010 Formulation Oral Drug: Itraconazole 400mg Oral', 'description': 'XEN1101 XPF-010 Formulation + Itraconazole\n\nPart 5 will explore the drug-drug interaction of XPF-010, when given with itraconazole (400mg, single dose, oral solution, fasted)', 'interventionNames': ['Drug: Itraconazole 400mg']}], 'interventions': [{'name': 'XPF-008', 'type': 'DRUG', 'description': 'Capsule filled with XEN1101', 'armGroupLabels': ['Drug: XEN1101 XPF-008 Formulation Oral']}, {'name': 'Microcrystalline Cellulose', 'type': 'DRUG', 'description': 'Placebo capsule', 'armGroupLabels': ['Placebo - Microcrystalline cellulose oral']}, {'name': 'XPF-010', 'type': 'DRUG', 'description': 'Capsule filled with XEN1101', 'armGroupLabels': ['Drug: XEN1101 XPF-008 Formulation Oral Drug: XEN1101 XPF-010 Formulation Oral', 'Drug: XEN1101 XPF-010 Formulation Oral']}, {'name': 'Itraconazole 400mg', 'type': 'DRUG', 'description': 'Oral', 'armGroupLabels': ['Drug: XEN1101 XPF-010 Formulation Oral Drug: Itraconazole 400mg Oral']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'SE1 1YR', 'city': 'London', 'country': 'United Kingdom', 'facility': 'Richmond Pharmacology Ltd.', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Gregory N Beatch, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Xenon Pharmaceuticals Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Xenon Pharmaceuticals Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}