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

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 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.

Official Title
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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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: GB-5001A
* Drug: GB-5001D
* Drug: Oral cohort


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 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: Parallel Assignment
Interventional Model Description: sequential
Masking: None (Open Label)


Arms and Interventions

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