Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DWP16001 After Oral Administration in Healthy Male Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Randomized, Double-blind, Placebo- and Active-controlled, Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of DWP16001 Following Oral Administration in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: DWP16001
* Drug: Placebo
* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male adults aged 19 to 50 at the time of screening test. Body weight between 50.0 kg and 90.0 kg and Body Mass Index (BMI) between 18.0 and 27.0. Written consent on voluntary decision of participation prior to the screening procedure after being fully informed of and completely understanding this study. Eligible to participate in the study by discretion of the investigator following medical examination by interview, physical examination, and clinical examination. Exclusion Criteria: Presence of a clinically significant hepatic, renal, nervous, respiratory, endocrine, blood•tumor, cardiovascular, urogenital, psychiatric disorder or prior history. 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. 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. 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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: DWP16001 Amg<br>DWP16001 Amg, tablets, orally, single dose administration | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 2: DWP16001 Bmg<br>DWP16001 Bmg, tablets, orally, single dose administration | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 3: DWP16001 Cmg<br>DWP16001 Cmg, tablets, orally, single dose administration | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 4: DWP16001 Dmg<br>DWP16001 Dmg, tablets, orally, single dose administration | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 5: DWP16001 Emg<br>DWP16001 Emg, tablets, orally, single dose administration | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 6: DWP16001 Fmg<br>DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days) | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 7: DWP16001 Gmg<br>DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days) | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 8: DWP16001 Hmg<br>DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days) | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 9: DWP16001 Img<br>DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days) | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|
| Experimental: Cohort 10: DWP16001 Jmg<br>DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days) | Drug: DWP16001<br>* DWP16001 tablets<br>Drug: Placebo<br>* DWP16001 placebo-matching tablets, Active control placebo-matching tablets<br>Drug: Dapagliflozin<br>* Forxiga®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of Participants With Adverse Events (AE) | All AE standardized using MedDRA was assessed by investigator using the protocol defined grading system. Intensity was categorized as mild, moderate and severe | Day -2(Randomization) to Day 8 12(Post-study visit) in single ascending dose or Day-3d to Day 22  (Post-study visit) | 
| Number and percentage of Participants With Adverse Drug Reactions (ADR) | An adverse drug reaction (ADR) is an injury caused by taking an investigational product | Day -2(Randomization) to Day 8 12(Post-study visit) in single ascending dose or Day-3d to Day 22  (Post-study visit) | 
| Number of Participants With Clinically Significant Vital Sign findings | Blood pressure, pulse and body temperature were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability | Day -2(Randomization) to Day 8 12(Post-study visit) in single ascending dose or Day-3d to Day 22  (Post-study visit) | 
| Number of Participants With Clinically Significant Electrocardiogram(12-lead ECG) findings | 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). | Day -2(Randomization) to Day 8 12(Post-study visit) in single ascending dose or Day-3d to Day 22  (Post-study visit) | 
| Number of Participants With Clinically Significant Laboratory results | Hematology, Blood chemistry, Coagulation and Urinalysis were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability. | Day -2(Randomization) to Day 8 12(Post-study visit) in single ascending dose or Day-3d to Day 22  (Post-study visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum concentration of DWP16001 | in single ascending dose cohort | 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 | 
| Cmax,ss: Maximum concentration of DWP16001 at steady state | in multiple ascending dose cohort | 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 | 
| Cmin,ss: Minimum concentration of DWP16001 at steady state | in multiple ascending dose cohort | 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 | 
| Time of maximum concentration | in single ascending dose cohort | 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 | 
| Tmax,ss: Time of maximum concentration at steady state | in multiple ascending dose cohort | 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 | 
| AUClast: Area under the plasma concentration-time curve from time 0 to 72hours | in single ascending dose cohort | 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 | 
| AUCinf: Area under the plasma concentration-time curve from time 0 to infinity | in single ascending dose cohort | 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 | 
| AUCtau: Area under the plasma concentration-time curve from time 0 to tau(dosing interval) | in multiple ascending dose cohort | 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 | 
| T1/2: Elimination half-life | in single ascending dose cohort | 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 | 
| T1/2: Elimination half-life | in multiple ascending dose cohort | 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 | 
| concentration of serum glucose | in single ascending dose cohort | 0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | 
| concentration of serum glucose | in multiple ascending dose cohort | Day 1 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 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 | 
| concentration of insulin | in multiple ascending dose cohort | 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 | 
| Changes from baseline for Body weight in kilograms | in multiple ascending dose cohort | Day -1 0 hour, Day 15 0 hour | 
| Changes from baseline for HbA1C in percent | in multiple ascending dose cohort | Day -1 0 hour, Day 15 0 hour | 
| concentration of Urine glucose excretion | in single ascending dose cohort | 0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hour | 
| concentration of Urine glucose excretion | in multiple ascending dose cohort | Day 1 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 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 |