Fed-Fasted, Single and Multiple Ascending Dose Trial of XEN-D0103

Study Overview
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Brief Summary
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This study is an evaluation of the safety and tolerability of XEN-D0103 in healthy subjects. Part 1 assesses the safety, tolerability and blood levels of the ascending single doses of XEN-D0103. Blood levels of XEN-D0103 will be assessed when administered with food and also without food in Part 2. The safety, tolerability and blood levels of XEN-D0103 will be assessed following dosing for 10 days in Part 3.

Official Title
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A Single Centre, Randomised, Double-blind, Placebo-controlled, Fed-fasted, Single and Multiple Ascending Dose Trial of XEN-D0103 in Healthy Subjects

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: 10mg XEN-D0103
* Drug: Placebo
* Drug: 30mg XEN-D0103
* Drug: 60mg XEN-D0103
* Drug: 120mg XEN-D0103
* Drug: 200mg XEN-D0103
* Drug: 150mg XEN-D0103


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Parts 1 and 3 healthy, male subjects aged 18 to 45 years, inclusive. For Part 2 healthy, male and female subjects aged 45 to 65 years, inclusive. Females must be of non-childbearing potential Exclusion Criteria: Subject has a known heart disease. Subject has any of QTcF > 450 msec, PR ≥ 210 msec or QRS ≥ 120 msec at screening (determined from median of three readings). For Part 1 only: subject has resting heart rate outside of the range 45 to 80 beats per minute (bpm) at screening (determined from median of three readings). Subject has any other condition which, in the investigator's opinion will interfere with the trial. Subject has a systolic blood pressure (BP) <80 or >160 mmHg at screening or a diastolic BP >90 or <45 mmHg at screening. Subject has a clinically significant abnormal laboratory test result at screening. Female subject who is pregnant or breast feeding and female subjects of childbearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Single Ascending Dose - Cohort 1<br>8 subjects (6 receiving 10mg XEN-D0103, 2 receiving placebo) | Drug: 10mg XEN-D0103<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part 1: Single Ascending Dose - Cohort 2<br>8 subjects (6 receiving 30mg XEN-D0103, 2 receiving placebo) | Drug: Placebo<br> <br> Drug: 30mg XEN-D0103<br> <br> |
| Experimental: Part 1: Single Ascending Dose - Cohort 3<br>8 subjects (6 receiving 60mg XEN-D0103, 2 receiving placebo) | Drug: Placebo<br> <br> Drug: 60mg XEN-D0103<br> <br> |
| Experimental: Part 1: Single Ascending Dose - Cohort 4<br>8 subjects (6 receiving 120mg XEN-D0103, 2 receiving placebo) | Drug: Placebo<br> <br> Drug: 120mg XEN-D0103<br> <br> |
| Experimental: Part 1: Single Ascending Dose - Cohort 5<br>8 subjects (6 receiving 200mg XEN-D0103, 2 receiving placebo) | Drug: Placebo<br> <br> Drug: 200mg XEN-D0103<br> <br> |
| Experimental: Part 2: Fed-Fasted<br>17 subjects receiving 200mg XEN-D0103 with either a high fat meal or following an overnight fast. | Drug: 200mg XEN-D0103<br> <br> |
| Experimental: Part 3: Multiple Ascending Dose - Cohort 1<br>10 subjects (8 receiving 30mg XEN-D0103 twice daily, 2 receiving placebo twice daily) | Drug: Placebo<br> <br> Drug: 30mg XEN-D0103<br> <br> |
| Experimental: Part 3: Multiple Ascending Dose - Cohort 2<br>10 subjects (8 receiving 60mg XEN-D0103 twice daily, 2 receiving placebo twice daily) | Drug: Placebo<br> <br> Drug: 60mg XEN-D0103<br> <br> |
| Experimental: Part 3: Multiple Ascending Dose - Cohort 3<br>10 subjects (8 receiving 150mg XEN-D0103 once daily, 2 receiving placebo once daily) | Drug: Placebo<br> <br> Drug: 150mg XEN-D0103<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events |  | Part 1: 13 days; Part 2: 13 days; Part 3: 22 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve (AUC) of XEN-D0103 following single and multiple dose administration |  | Part 1: 13 days; Part 3: 22 days | 
| Food effect on AUC of XEN-D0103 |  | 13 days | 
| Change in QTcF with XEN-D0103 and with placebo |  | 2 days |