Healthy
Conditions
Brief summary
This is a dose block-randomized, double-blind, placebo- and active-controlled, single and multiple dosing, dose-escalation clinical phase 1 trial to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of DWP16001 after oral administration in healthy male volunteers.
Interventions
DRUGDWP16001
DWP16001 tablets
DRUGPlacebo
DWP16001 placebo-matching tablets, Active control placebo-matching tablets
DRUGDapagliflozin
Forxiga®
Sponsors
Daewoong Pharmaceutical Co. LTD.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
19 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male adults aged 19 to 50 at the time of screening test. 2. Body weight between 50.0 kg and 90.0 kg and Body Mass Index (BMI) between 18.0 and 27.0. 3. Written consent on voluntary decision of participation prior to the screening procedure after being fully informed of and completely understanding this study. 4. Eligible to participate in the study by discretion of the investigator following medical examination by interview, physical examination, and clinical examination.
Exclusion criteria
1. Presence of a clinically significant hepatic, renal, nervous, respiratory, endocrine, blood•tumor, cardiovascular, urogenital, psychiatric disorder or prior history. 2. Presence or prior history of a gastrointestinal disorder (e.g., gastrointestinal ulcers, gastritis, stomach cramps, gastroesophageal reflux disease, Crohn's disease, etc.), or prior history of surgery (except for simple appendectomy or hernia surgery) that may affect safety and PK/PD assessment. 3. Hypersensitivity to a drug containing an ingredient of the investigational product (DWP16001), Dapagliflozin or similar ingredient or other drugs (e.g., aspirin, antibiotics, etc.) or medical history of clinically significant hypersensitivity. 4. Following laboratory abnormalities identified during the screening test: * AST (SGOT), ALT (SGPT) \>1.5 upper limit of normal range * Creatinine clearance calculated by the MDRD equation \< 90 mL/min * Repeatedly confirmed QTc interval \> 450 ms * Fasting serum glucose \> 110mg/dL or \< 70mg/dL * Serum HbA1c \> 6.5 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and percentage of Participants With Adverse Events (AE) | Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit) | All AE standardized using MedDRA was assessed by investigator using the protocol defined grading system. Intensity was categorized as mild, moderate and severe |
| Number and percentage of Participants With Adverse Drug Reactions (ADR) | Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit) | An adverse drug reaction (ADR) is an injury caused by taking an investigational product |
| Number of Participants With Clinically Significant Vital Sign findings | Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit) | Blood pressure, pulse and body temperature were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability |
| Number of Participants With Clinically Significant Electrocardiogram(12-lead ECG) findings | Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit) | Ventricular rate, RR interval, PR interval, QRS duration, QTcB and QTcF were recorded. The results of 12-lead ECG will be categorized Normal/Abnormal NCS(No clinically significant)/Abnormal CS(clinically significant). |
| Number of Participants With Clinically Significant Laboratory results | Day -2(Randomization) to Day 8~12(Post-study visit) in single ascending dose or Day-3d to Day 22~ (Post-study visit) | Hematology, Blood chemistry, Coagulation and Urinalysis were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUClast: Area under the plasma concentration-time curve from time 0 to 72hours | 0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour | in single ascending dose cohort |
| AUCinf: Area under the plasma concentration-time curve from time 0 to infinity | 0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour | in single ascending dose cohort |
| AUCtau: Area under the plasma concentration-time curve from time 0 to tau(dosing interval) | Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | in multiple ascending dose cohort |
| T1/2: Elimination half-life | 0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour | in single ascending dose cohort |
| Cmax: Maximum concentration of DWP16001 | 0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour | in single ascending dose cohort |
| concentration of insulin | Day -1 pre dose, 0.5, 1, 1.5, 2, 3, 4 hour, Day 15 pre dose, 0.5, 1, 1.5, 2, 3, 4 hour | in multiple ascending dose cohort |
| Changes from baseline for Body weight in kilograms | Day -1 0 hour, Day 15 0 hour | in multiple ascending dose cohort |
| Changes from baseline for HbA1C in percent | Day -1 0 hour, Day 15 0 hour | in multiple ascending dose cohort |
| concentration of Urine glucose excretion | 0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | in single ascending dose cohort |
| concentration of serum glucose | 0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | in single ascending dose cohort |
| Cmax,ss: Maximum concentration of DWP16001 at steady state | Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | in multiple ascending dose cohort |
| Cmin,ss: Minimum concentration of DWP16001 at steady state | Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | in multiple ascending dose cohort |
| Time of maximum concentration | 0 hour (pre-dose), 0.25 hour, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12hour, 24 hour, 36 hour, 48 hour, 72 hour | in single ascending dose cohort |
| Tmax,ss: Time of maximum concentration at steady state | Day1 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour, Day 4, 7, 10, 13 0 hour (pre dose), Day 15 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | in multiple ascending dose cohort |
Countries
South Korea
Outcome results
None listed