A Study to Compare the Pharmacokinetics of BR4002 and BR4002-1 in Healthy Volunteers

NCT04462029 | Completed Early Phase 1

• 1 other identifier: BR-DPZ-CT-102
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed as a randomized, open-label, single-dose, 6x3 crossover study.

Conditions

Dementia Alzheimers

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic variables -Area Under the concentration-time Curve from time 0 to t after single dosing(AUCt) of BR4002 and BR4002-1

  PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.

  0~240 hours after medication

• Pharmacokinetic variables - maximum observed plasma concentration(Cmax) of BR4002 and BR4002-1

  PK data of subjects who complete all of the scheduled blood collections without any major protocol deviations considered to affect the PK results after administration of the IP and have quantifiable drug concentrations for PK assessment will be analyzed.

  0~240 hours after medication

Secondary Outcomes (2)

• Pharmacokinetic variables - Area Under the concentration-time Curve from time 0 to infinite after single dosing(AUCinf) of BR4002 and BR4002-1

  0~240 hours after medication

• Pharmacokinetic variables - Time of occurrence of Cmax(Tmax) of BR4002 and BR4002-1

  0~240 hours after medication

Study Arms (6)

sequence 1

OTHER

A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated. * R(Reference): BR4002-1 (oral intake) 5mg single-dose * T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator) * T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator) sequence 1: R - T1 - T2

Drug: BR4002; Drug: BR4002-1

sequence 2

OTHER

A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated. * R(Reference): BR4002-1 (oral intake) 5mg single-dose * T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator) * T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator) sequence 2: R - T2 - T1

Drug: BR4002; Drug: BR4002-1

sequence 3

OTHER

A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated. * R(Reference): BR4002-1 (oral intake) 5mg single-dose * T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator) * T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator) sequence 3: T1 - R - T2

Drug: BR4002; Drug: BR4002-1

sequence 4

OTHER

A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated. * R(Reference): BR4002-1 (oral intake) 5mg single-dose * T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator) * T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator) sequence 4: T1 - T2 - R

Drug: BR4002; Drug: BR4002-1

sequence 5

OTHER

A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated. * R(Reference): BR4002-1 (oral intake) 5mg single-dose * T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator) * T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator) sequence 5: T2 - R - T1

Drug: BR4002; Drug: BR4002-1

sequence 6

OTHER

A total of 18 subjects will be randomized into 6 sequence groups. The investigational products (IPs) will be administered according to the treatment groups (R, T1, and T2) assigned to each sequence group in Period 1, Period 2, and Period 3. In between each period, there will be a washout period (28 days) long enough for the administered IP to be metabolized and eliminated. * R(Reference): BR4002-1 (oral intake) 5mg single-dose * T1(Test1): BR4002 (patch) 5mg single-dose (using the applicator) * T2(Test2): BR4002 (patch) 5mg single-dose (not using the applicator) sequence 6: T2 - T1 - R

Drug: BR4002; Drug: BR4002-1

Interventions

BR4002 DRUG

* Administration to the T1 group: 5 mg of BR4002 (patch) will be attached using an applicator for 24 hours * Administration to the T2 group: 5 mg of BR4002 (patch) will be attached without using an applicator for 24 hours

sequence 1; sequence 2; sequence 3; sequence 4; sequence 5; sequence 6

BR4002-1 DRUG

Administration to the R group: 5 mg of BR4002-1 (oral formulation) will be administered with 150 mL of water

sequence 1; sequence 2; sequence 3; sequence 4; sequence 5; sequence 6

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged ≥ 19 and ≤ 55 years at screening
• Body weight of ≥ 50 kg with calculated body mass index (BMI) of ≥ 18.0 to ≤ 29.0 kg/m2
• Determined eligible based on the results of physical examination and investigator questioning conducted according to this protocol. That is, absence of congenital or chronic disease, and absence of pathological symptoms or findings based on medical examination in the last 3 years.
• Determined eligible based on the results of the laboratory tests and electrocardiogram (ECG) conducted according to this protocol
• Voluntarily decided to participate in the study and provided written consent to follow precautions after receiving a detailed explanation on this study and fully understanding the information

You may not qualify if:

• Hypersensitivity to, or history of clinically significant hypersensitivity to donepezil hydrochloride, piperidine derivatives or any ingredients of piperidine derivatives, or other drugs (aspirin, antibiotics, etc.)
• Hereditary disorders including galactose intolerance, Lapp lactase deficiency, and glucose-galactose malabsorption
• History of heart disease such as sinus node syndrome, intra-atrial conduction disturbance or atrioventricular junctional conduction disturbance
• Ongoing administration of non-steroidal anti-inflammatory drugs or history of peptic ulcer
• History of asthma or obstructive pulmonary disease
• Extrapyramidal disorder
• Psychotic disorders or drug addiction
• Presence or prior history of a gastrointestinal disorder or prior history of gastrointestinal surgery or skin graft that may affect the absorption of the IP
• Presence or prior history of clinically significant cardiovascular, respiratory, hepatic, renal, neurological, endocrine, hematological and oncological, psychotic, or urinary disease
• Clinically significant hypotension (systolic blood pressure \< 90 mmHg) or hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 95 mmHg) at screening
• Any of the following results from screening tests:
• AST or ALT \> 2 times the upper limit of normal
• Total bilirubin \> 2.0 mg/dL
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2
• QTc \> 450 ms or any clinically significant abnormal finding from an ECG result at screening

Sponsors & Collaborators

• Boryung Pharmaceutical Co., Ltd: lead

Study Sites (1)

Inha University Hospital

Incheon, South Korea

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Sang-Heon Cho

  Inha University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 8, 2020
• Study Start: June 5, 2020
• Primary Completion: October 7, 2020
• Study Completion: October 7, 2020
• Last Updated: October 28, 2020

Record last verified: 2020-10

Locations

KR (1)