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

NCT05525780 | Completed Phase 1

• 1 other identifier: G2GBio
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (5)

• Key PK parameters for single dose IM and Oral cohorts

  Day 64

• Key PK parameters for single dose IM and Oral cohorts

  Day 64

• Key PK parameters for single dose IM and Oral cohorts

  Day 64

• Key PK parameters for single dose IM and Oral cohorts

  Day 64

• Key PK parameters for single dose IM and Oral cohorts

  Day 64

Study Arms (3)

GB-5001

EXPERIMENTAL

GB-5001 Suspension for intramuscular (IM) injection at three doses

Drug: GB-5001

Placebo

PLACEBO COMPARATOR

Placebo Suspension for intramuscular (IM) injection, Volume to be matched with the active drug in the respective cohort

Drug: Placebo

Oral cohort

ACTIVE COMPARATOR

Aricept® tablet

Drug: Oral cohort

Interventions

GB-5001 DRUG

Depending on the cohort, volume will be varied to administer.

GB-5001

Placebo DRUG

A matched volume of placebo product will be administered to each subject in each cohort.

Placebo

Oral cohort DRUG

Single dose of Aricept tablet

Oral cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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".

You may not qualify if:

• 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.

Sponsors & Collaborators

• G2GBio, Inc.: lead

Study Sites (1)

Syneos Health

Québec, Canada

Location

Related Publications (1)

• Khwarg J, Lee H, Yu KS, Seol E, Chung JY. Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants. Neurol Ther. 2024 Oct;13(5):1453-1466. doi: 10.1007/s40120-024-00643-4. Epub 2024 Aug 10.

  PMID: 39126603 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Cohort Studies

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Epidemiologic Studies; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: September 2, 2022
• Study Start: August 26, 2022
• Primary Completion: June 2, 2023
• Study Completion: June 2, 2023
• Last Updated: July 13, 2023

Record last verified: 2023-07

Locations

CA (1)