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

August 19, 2019 updated by: Daewoong Pharmaceutical Co. LTD.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

123

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and percentage of Participants With Adverse Events (AE)
Time Frame: 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
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)
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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).
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
Time Frame: 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.
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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)
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: Day -1 0 hour, Day 15 0 hour
in multiple ascending dose cohort
Day -1 0 hour, Day 15 0 hour
Changes from baseline for HbA1C in percent
Time Frame: Day -1 0 hour, Day 15 0 hour
in multiple ascending dose cohort
Day -1 0 hour, Day 15 0 hour
concentration of Urine glucose excretion
Time Frame: 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
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
Time Frame: 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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daewoong Pharmaceutical Co. LTD.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 3, 2017

Primary Completion (ACTUAL)

May 21, 2019

Study Completion (ACTUAL)

July 30, 2019

Study Registration Dates

First Submitted

November 29, 2017

First Submitted That Met QC Criteria

December 6, 2017

First Posted (ACTUAL)

December 7, 2017

Study Record Updates

Last Update Posted (ACTUAL)

August 21, 2019

Last Update Submitted That Met QC Criteria

August 19, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DW_DWP16001001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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