Single Ascending Dose Study to Investigate the Safety and Pharmacokinetics of XC101-D13H in Healthy Adult Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-group single ascending dose (SAD) study. There are 4 cohorts of 8 subjects (8 active and 2 placebo) planned for evaluation under fasting conditions. One of the planned dose levels will cross over after a washout period to receive the same single dose of XC101-D13H or placebo under fed conditions.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, parallel-group single ascending dose (SAD) study. There are 4 cohorts of 8 subjects (8 active and 2 placebo) planned for evaluation under fasting conditions. One of the planned dose levels will cross over after a washout period to receive the same single dose of XC101-D13H or placebo under fed conditions. Dose escalation will be supervised by a Safety Monitoring Board (SMB). Dose escalation to the next dose level will not take place until the SMB has determined that adequate safety, tolerability, PK, and core-lab analyzed ECGs from the previous cohort and all previous cohorts have been demonstrated to permit proceeding to the next cohort. PK data from all available cohorts will be used to guide the dose-escalation decisions.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of XC101-D13H in Healthy Adult Subjects

Conditions
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Migraine

Intervention / Treatment
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* Drug: XC101-D13H
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Healthy, adult, male or female of non childbearing potential only, 18-55 years of age, inclusive, at screening. Body mass index (BMI) ≥ 18 and ≤ 30.0 kg/m2 at screening. Medically healthy with no clinically significant finding in medical history, physical examination, laboratory profiles, vital signs, or ECGs, as judged by the PI or designee. Creatinine must be within the upper limit of normal at screening. Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol. Major Exclusion Criteria: Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. History or presence of clinically significant medical, surgical, clinical laboratory, or psychiatric condition or disease. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study. History of clinically significant hypotension. History of lightheadedness, dizziness or syncope in the 12 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XC101-D13H<br>single dose | Drug: XC101-D13H<br>* XC101-D13H supplied as 0.4, 0.8, 1.6 or 3.2 mg dose, administered in capsules<br>|
| Placebo Comparator: Placebo<br>single dose | Drug: Placebo<br>* Placebo supplied as matching capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events | Adverse Events will be monitored throughout confinement in the clinic and through the 14-day follow-up visit. | pre-dose through 14 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration [Cmax] of XC101-D13H | Blood samples will be collected pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours post-dose and the maximum observed concentration for XC101-D13H will be calculated. | 48 hours | 
| Area under the curve [AUC] of XC101-D13H | Blood samples will be collected pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours post-dose and the area under the concentration-time curve, from time 0 to the last observed non-zero concentration will be calculated for XC101-D13H. | 48 hours | 
| Time to reach maximum plasma concentration [Tmax] of XC101-D13H | Blood samples will be collected pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours post-dose and the time to reach the maximum plasma concentration of XC101-D13H will be calculated. | 48 hours |