A Study to Evaluate Safety, Tolerability and Pharmacokinetics of DA-8010 in Healthy Subjects

Study Overview
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Brief Summary
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This study is a Phase I, Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate Safety, Tolerability and Pharmacokinetics After Single and Multiple Oral Administration of DA-8010 in Healthy Subjects.

Detailed Description
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This study will be a randomised, double-blind, placebo-controlled, dose-escalation, single and multiple oral dose study conducted in 2 parts. In Part A, each subject will participate in 1 treatment period only and reside at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 3 (48 hours postdose), except for Group A4, where each subject will participate in 2 treatment periods separated by a minimum of 13 days to evaluate the effect of food. In Part B, each subject will participate in 1 treatment period only and reside at the CRU from Day -1 (1 day before dosing) until the morning of Day 9 (48 hours after the final dose on Day 7).

Official Title
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A Phase I, Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate Safety, Tolerability and Pharmacokinetics After Single and Multiple Oral Administration of DA-8010 in Healthy Subjects

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: DA-8010
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 18.0 and 32.0 kg/m2 Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions Exclusion Criteria: Subjects who do not agree to use a method of acceptable contraception Female subjects of child-bearing potential who do not agree to use a highly effective method of birth control Consume more than 28 or 21 units of alcohol per week if male or female, respective Subjects who have used nicotine-containing products (including cigarettes), within 3 months prior to the first dose administration Subjects who have used, or intend to use the product like non-prescribed systemic or topical medication, herbal remedy, vitamin/mineral supplement, within 7 days of the first dose administration Systolic blood pressure < 90 mmHg or > 140 mmHg Diastolic blood pressure < 50 mmHg or > 90 mmHg Pulse rate < 45 bpm or > 100 bpm Positive urine drugs of abuse screen at screening or first admission Positive alcohol breath test at screening or first admission Positive cotinine test at screening or first admission Abnormality in the 12-lead ECG at screening, admission or predose on Day 1 Subjects who are pregnant, breastfeeding, or lactating Subjects who are still participating in another clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of any investigational drug in the past 3 months prior to the first dose administration Subjects who have a significant history of drug allergy, as determined by the Investigator Aspartate aminotransferase and/or Alanine aminotransferase ≥ 1.5 × upper limit of normal (ULN) or total bilirubin > ULN at screening or admission Subjects who are carriers of HBsAg or hepatitis C antibody, have serum hepatitis or positive result for the test for HIV antibodies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active in Group A1 A7<br>In each of Groups A1 to A7, 8 subjects will receive DA-8010. | Drug: DA-8010<br>* Part A will comprise a single-dose, sequential-group study incorporating a food effect evaluation. Total 70 subjects will be studied in 7 groups (Groups A1 to A7); 60 male and 10 female. Each group will consist of 10 subjects of the same sex and 8 subject for DA-8010. Part B will comprise a multiple-dose, sequential-group study. Total forty subjects (30 male and 10 female) will be studied in 4 groups (Groups B1 to B4), with each group consisting of 10 subjects of the same sex and 8 subject for DA-8010.<br>|
| Placebo Comparator: Placebo in Group A1 A7<br>In each of Groups A1 to A7, 2 subjects will receive placebo. | Drug: Placebo<br>* Part A will comprise a single-dose, sequential-group study incorporating a food effect evaluation. Total 70 subjects will be studied in 7 groups (Groups A1 to A7); 60 male and 10 female. Each group will consist of 10 subjects of the same sex and 2 subject for DA-8010. Part B will comprise a multiple-dose, sequential-group study. Total forty subjects (30 male and 10 female) will be studied in 4 groups (Groups B1 to B4), with each group consisting of 10 subjects of the same sex and 2 subject for DA-8010.<br>|
| Active Comparator: Active in Group B1 B4<br>In each of Groups B1 to B4, 8 subjects will receive DA-8010. | Drug: DA-8010<br>* Part A will comprise a single-dose, sequential-group study incorporating a food effect evaluation. Total 70 subjects will be studied in 7 groups (Groups A1 to A7); 60 male and 10 female. Each group will consist of 10 subjects of the same sex and 8 subject for DA-8010. Part B will comprise a multiple-dose, sequential-group study. Total forty subjects (30 male and 10 female) will be studied in 4 groups (Groups B1 to B4), with each group consisting of 10 subjects of the same sex and 8 subject for DA-8010.<br>|
| Placebo Comparator: Placebo in Group B1 B4<br>In each of Groups B1 to B4, 2 subjects will receive placebo. | Drug: Placebo<br>* Part A will comprise a single-dose, sequential-group study incorporating a food effect evaluation. Total 70 subjects will be studied in 7 groups (Groups A1 to A7); 60 male and 10 female. Each group will consist of 10 subjects of the same sex and 2 subject for DA-8010. Part B will comprise a multiple-dose, sequential-group study. Total forty subjects (30 male and 10 female) will be studied in 4 groups (Groups B1 to B4), with each group consisting of 10 subjects of the same sex and 2 subject for DA-8010.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Safety outcome will be assessed by incidence and severity of several items (adverse events, vital signs, electrocardiography, clinical laboratory evaluations, physical examination). | during 10 days in Part A | 
| Safety and Tolerability | Safety outcome will be assessed by incidence and severity of several items (adverse events, vital signs, electrocardiography, clinical laboratory evaluations, physical examination). | during 16 days in Part B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) |  | 48 hours | 
| Maximum observed plasma concentration (Cmax) |  | 48 hours | 
| Time of the maximum observed plasma concentration (tmax) |  | 48 hours |