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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: GB-5001; Drug: Placebo; Drug: Oral cohort

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Syneos Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GB-5001; GB-5001 Suspension for intramuscular (IM) injection at three doses	Drug: GB-5001; Depending on the cohort, volume will be varied to administer.
Placebo Comparator: Placebo; Placebo Suspension for intramuscular (IM) injection, Volume to be matched with the active drug in the respective cohort	Drug: Placebo; A matched volume of placebo product will be administered to each subject in each cohort.
Active Comparator: Oral cohort; Aricept® tablet	Drug: Oral cohort; Single dose of Aricept tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: G2GBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): June 2, 2023

Study Registration Dates

• First Submitted: August 23, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: G2GBio

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No