Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics From Single Dose of Intramuscular (IM) and Subcutaneous (SC) Donepezil (GB-5001) Injections Versus Donepezil Oral Tablet (Aricept®) in Healthy Male Volunteers

An Open-label, Active-controlled, Parallel and Dose-escalation, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Intramuscular (IM) and Subcutaneous (SC) Donepezil (GB-5001) Injections Versus Donepezil Oral Tablet (Aricept®) in Healthy Male Volunteers

This study is to evaluate the safety and tolerability of single dose of GB-5001 (donepezil) IM and SC depot in healthy male Adults. And, It is to evaluate pharmacokinetic characteristics of GB-5001 (donepezil) IM and SC single dose injection vs. active comparator.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: GB-5001A; Drug: GB-5001D; Drug: Oral cohort

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jimin Hwang; Phone Number: 82-2-400-2681; Email: clinicalstudy@g2gbio.com
• Study Contact Backup: Name: Sangsub Lee; Phone Number: 82-2-400-2694; Email: clinicalstudy@g2gbio.com

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of
    • Recruiting
    • Chungnam national university hospital
    • Contact: Hong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adult males,19 to 55 years of age, inclusive at the time of screening visit
• Subject with a body weight of 55 kg or more and a body mass index (BMI) equal to or greater than 18.5 kg/m² but less than 30 kg/m²
• Subject without congenital or chronic conditions, and with no pathological symptoms or findings on internal medical examination
• Subject who has been deemed suitable based on screening test results assessed by the principal investigator
• Subject who can understand this clinical trial, provide informed written consent prior to the clinical trial procedures

Exclusion Criteria:

• Subjects with the following medical history or symptoms, as determined by the Principal Investigator to pose a risk to the trial.

  • Renal/Genitourinary, Gastrointestinal, Cardiovascular, Cerebrovascular, Pulmonary, Endocrine, Immune, Musculoskeletal, Neurological, Psychiatric, Dermatological, and Hematological conditions.
  • Rhabdomyolysis
  • Seizure, Epilepsy, Fainting
  • peptic ulcer or gastrointestinal hemorrhage
  • Gastrointestinal pathology, uncontrollable gastrointestinal symptoms or a history of disturbing absorption, distribution, metabolism or excretion
  • Severe physical/organ abnormalities
  • Human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus

• Subjects with a history of, or currently receiving, the following medications, as determined by the Principal Investigator regarded as a risk to the trial.

  • Medications, including antidepressants, that can induce Rhabdomyolysis
  • Medications with a risk of ulcer development.
  • Potent inhibitors of cytochrome P450 (CYP) enzymes
  • Anticholinergic drugs, cholinomimetics, and other cholinesterase inhibitors
• Subjects who have difficulty with venipuncture or injection procedures via catheter or intravenous access
• Subjects who have been consistently engaging in excessive smoking or consuming caffeine or alcohol within the last 3 months prior to screening, or Subjects who cannot abstain from smoking, caffeine, and alcohol consumption for at least 2 days before the scheduled administration of the investigational product or during the inpatient period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GB-5001A; GB-5001 Suspension for IM/SC injection at three doses(low, intermediate, high) The cohort is determined through random allocation.	Drug: GB-5001A; Depending on the cohort, volume will be varied to administer, and the dosage and route of administration may be varied.
Experimental: GB-5001D; GB-5001 Suspension for SC injection at three doses(low, intermediate, high) The cohort is determined through random allocation.	Drug: GB-5001D; Depending on the cohort, volume will be varied to administer.
Active Comparator: Oral cohort; Aricept® tablet. The cohort is determined through random allocation.	Drug: Oral cohort; Single dose of Aricept tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of participants with adverse events	Part A: Cohort A, B : Upto Day 106 / Cohort C : Upto Day 71 / Cohort D : Upto Day 18, Part B: Cohort E, F, M : Upto Day 18 or Day 106
Clinical Laboratory tests	Incidence of abnormal clinically significant clinical laboratory test results. (Hematology, Blood Chemistry Test, Urine Test, Blood Coagulation Test, Serum Test and Urine Drug Screening Test.) /Day 1 to Day	Part A: Cohort A, B : Upto Day 99 / Cohort C : Upto Day 64 / Cohort D : Upto Day 11, Part B: Cohort E, F, M : Upto Day 64 or Day 99
Vital Signs	Incidence of abnormal clinically significant vital signs.(Systolic and Diastolic Blood Pressure, Pulse Rate, Body Temperature)	Part A: Cohort A, B : Upto Day 99 / Cohort C : Upto Day 64 / Cohort D : Upto Day 11, Part B: Cohort E, F, M : Upto Day 64 or Day 99
Physical examination	Incidence of abnormal clinically significant Physical examination. (This includes an evaluation of the overall appearance and a review of the physical organ systems through questioning, visual inspection, and palpation.)	Part A: Cohort A, B : Upto Day 99 / Cohort C : Upto Day 64 / Cohort D : Upto Day 11, Part B: Cohort E, F, M : Upto Day 64 or Day 99
Electrocardiograms	Incidence of abnormal clinically significant ECG results (Ventricular rate (beats/min), PR interval (msec), QRS (msec), QT (msec), QTc (msec)	Part A: Cohort A, B : Upto Day 99 / Cohort C : Upto Day 64 / Cohort D : Upto Day 11, Part B: Cohort E, F, M : Upto Day 64 or Day 99

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (Cmax)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (Tmax)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (Tlag)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (AUCinf)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (AUClast)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (AUC 0-762)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (CL/F)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (Vd/F)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99
Pharmacokinetics (t1/2)	Part A: Cohort A, B : upto Day 99 / Cohort C : upto Day 64 / Cohort D : Upto Day 11 , Part B: Cohort E, F, M : upto Day 11 or Day 99

Collaborators and Investigators

• Sponsor: G2GBio, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): January 3, 2024
• Primary Completion (Estimated): September 17, 2024
• Study Completion (Estimated): January 14, 2025

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 9, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: November 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: GB5001A101

Drug and device information, study documents

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