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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: DWP16001; Drug: Placebo; Drug: Dapagliflozin

• Registration Number: NCT03364985
• Lead Sponsor: Daewoong Pharmaceutical Co. LTD.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-29
• Study Start: 2017-12-03
• Study First Submitted QC: 2017-12-06
• Study First Posted: 2017-12-07
• Primary Completion: 2019-05-21
• Study Completion: 2019-07-30
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-19
• Last Update Posted: 2019-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 123

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: DWP16001 Amg	DWP16001	DWP16001 Amg, tablets, orally, single dose administration
Cohort 1: DWP16001 Amg	Placebo	DWP16001 Amg, tablets, orally, single dose administration
Cohort 2: DWP16001 Bmg	DWP16001	DWP16001 Bmg, tablets, orally, single dose administration
Cohort 2: DWP16001 Bmg	Placebo	DWP16001 Bmg, tablets, orally, single dose administration
Cohort 2: DWP16001 Bmg	Dapagliflozin	DWP16001 Bmg, tablets, orally, single dose administration
Cohort 3: DWP16001 Cmg	DWP16001	DWP16001 Cmg, tablets, orally, single dose administration
Cohort 3: DWP16001 Cmg	Placebo	DWP16001 Cmg, tablets, orally, single dose administration
Cohort 4: DWP16001 Dmg	DWP16001	DWP16001 Dmg, tablets, orally, single dose administration
Cohort 4: DWP16001 Dmg	Placebo	DWP16001 Dmg, tablets, orally, single dose administration
Cohort 5: DWP16001 Emg	DWP16001	DWP16001 Emg, tablets, orally, single dose administration
Cohort 5: DWP16001 Emg	Placebo	DWP16001 Emg, tablets, orally, single dose administration
Cohort 6: DWP16001 Fmg	DWP16001	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 6: DWP16001 Fmg	Placebo	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 7: DWP16001 Gmg	DWP16001	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 7: DWP16001 Gmg	Placebo	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 8: DWP16001 Hmg	DWP16001	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 8: DWP16001 Hmg	Placebo	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 9: DWP16001 Img	DWP16001	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 9: DWP16001 Img	Placebo	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 10: DWP16001 Jmg	DWP16001	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 10: DWP16001 Jmg	Placebo	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 1: DWP16001 Amg	Dapagliflozin	DWP16001 Amg, tablets, orally, single dose administration
Cohort 3: DWP16001 Cmg	Dapagliflozin	DWP16001 Cmg, tablets, orally, single dose administration
Cohort 4: DWP16001 Dmg	Dapagliflozin	DWP16001 Dmg, tablets, orally, single dose administration
Cohort 5: DWP16001 Emg	Dapagliflozin	DWP16001 Emg, tablets, orally, single dose administration
Cohort 6: DWP16001 Fmg	Dapagliflozin	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 9: DWP16001 Img	Dapagliflozin	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 7: DWP16001 Gmg	Dapagliflozin	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 8: DWP16001 Hmg	Dapagliflozin	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)
Cohort 10: DWP16001 Jmg	Dapagliflozin	DWP16001 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 15days)

Primary Outcome Measures

Name	Time	Method
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 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.
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 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).

Secondary Outcome Measures

Name	Time	Method
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
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
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	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
concentration of serum glucose	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	in multiple 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	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	in multiple ascending dose cohort

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of