Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Donepezil From Single Dose of GB-5001 IM Depot and Aricept® Oral Tablets in Healthy Male Volunteers

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of single dose of GB-5001 (donepezil) IM depot in healthy male volunteers. And, it is to predict the multiple-dose pharmacokinetics based on the single-dose pharmacokinetics of GB-5001 IM depot and the oral Aricept® (donepezil hydrochloride) tablet by PK modeling.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Donepezil From Single Dose of GB-5001 Intramuscular Depot and Aricept® Oral Tablets (Pfizer Canada Inc.) in Healthy Male Volunteers

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: GB-5001
* Drug: Placebo
* Drug: Oral cohort


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, non-smoking male volunteers, 18-55 years of age, inclusive at the time of informed consent. Body mass index (BMI) that is within 18.5 - 30.0 kg/m2, inclusive, and weight at least 55 kg and above. Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator. Systolic blood pressure between 95-140 mmHg, inclusive, and diastolic blood pressure between 55-90 mmHg, inclusive, and heart rate between 60-100 bpm, inclusive, unless deemed otherwise by the PI/Sub-Investigator. Clinical laboratory values within the clinical site's most recent acceptable laboratory test range, and/or values are deemed by the PI/Sub-Investigator as Not Clinically Significant. Exclusion Criteria: Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator. Known history or presence of seizure or convulsion, unless determined as not clinically significant by the PI/Sub-Investigator. Known history or presence of peptic ulcer or gastrointestinal bleeding within 3 months prior to study drug administration, unless determined as not clinically significant by the PI/Sub-Investigator. Known risk of developing ulcers (for example, if you are taking non-steroidal anti-inflammatory drugs [NSAIDS] or high doses of acetylsalicylic acid [ASA] [Aspirin®]), unless determined as not clinically significant by the PI/Sub-Investigator. Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug experienced within 7 days prior to study drug administration, as determined by the PI/Sub-Investigator. Presence of any clinically significant illness within 30 days prior to dosing, as determined by the PI/Sub-Investigator Presence of any clinically significant illness within 30 days prior to dosing, as determined by the PI/Sub-Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: GB-5001<br>GB-5001 Suspension for intramuscular (IM) injection at three doses | Drug: GB-5001<br>* Depending on the cohort, volume will be varied to administer.<br>|
| Placebo Comparator: Placebo<br>Placebo Suspension for intramuscular (IM) injection, Volume to be matched with the active drug in the respective cohort | Drug: Placebo<br>* A matched volume of placebo product will be administered to each subject in each cohort.<br>|
| Active Comparator: Oral cohort<br>Aricept® tablet | Drug: Oral cohort<br>* Single dose of Aricept tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity, and dose-relationship of AEs |  | Day 64 | 
| Vital signs | blood pressure [BP], respiratory rate [RR], heart rate [HR], and temperature | Day 64 | 
| Electrocardiograms |  | Day 64 | 
| Physical examination | Height, weight, and BMI will be recorded | Day 64 | 
| Injection site assessments |  | Day 64 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key PK parameters for single dose IM and Oral cohorts | AUCt: area under the plasma concentration vs time curve from time 0 to the time of the last measurable concentration | Day 64 | 
| Key PK parameters for single dose IM and Oral cohorts | Cmax: maximum observed plasma concentration | Day 64 | 
| Key PK parameters for single dose IM and Oral cohorts | tmax: time to maximum observed plasma concentration | Day 64 | 
| Key PK parameters for single dose IM and Oral cohorts | λz: terminal elimination rate constant | Day 64 | 
| Key PK parameters for single dose IM and Oral cohorts | t½: terminal elimination half-life | Day 64 |