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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03364985
• Other study ID #: DW_DWP16001001
• Status: Completed
• Phase: Phase 1
• Start date: December 3, 2017
• Est. completion date: July 30, 2019

Study information

• Verified date: August 2019
• Source: Daewoong Pharmaceutical Co. LTD.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: July 30, 2019
• Est. primary completion date: May 21, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• DWP16001
DWP16001 tablets
• Placebo
DWP16001 placebo-matching tablets, Active control placebo-matching tablets
• Dapagliflozin
Forxiga®

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Daewoong Pharmaceutical Co. LTD.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes from baseline for Body weight in kilograms	in multiple ascending dose cohort	Day -1 0 hour, Day 15 0 hour
Secondary	Changes from baseline for HbA1C in percent	in multiple ascending dose cohort	Day -1 0 hour, Day 15 0 hour
Secondary	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
Secondary	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