Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DWP14012 After Oral Administration in Healthy Male Volunteers

Sponsor

Daewoong Pharmaceutical Co. LTD. (Industry)

Overall Status

Completed

CT.gov ID

NCT02757144

Collaborator

(none)

120

Enrollment

Location

Arms

11.1

Actual Duration (Months)

10.8

Patients Per Site Per Month

Study Details

Study Description

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 DWP14012 after oral administration in healthy male volunteers.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: DWP14012 Drug: Placebo Drug: Esomeprazole	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

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 DWP14012 After Oral Administration in Healthy Male Volunteers

Actual Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Feb 1, 2017

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: DWP14012 Amg DWP14012 Amg, tablets, orally, single dose administration	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 2: DWP14012 Bmg DWP14012 Bmg, tablets, orally, single dose administration	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 3: DWP14012 Cmg DWP14012 Cmg, tablets, orally, single dose administration	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 4: DWP14012 Dmg DWP14012 Dmg, tablets, orally, single dose administration	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 5: DWP14012 Emg DWP14012 Emg, tablets, orally, single dose administration	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 6: DWP14012 Fmg DWP14012 Emg, tablets, orally, single dose administration	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Placebo Comparator: Cohort 1-6: Placebo DWP14012 placebo-matching tablets, Active-control placebo-matching tablets, orally, single dose administration	Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Active Comparator: Cohort 1-6: Esomeprazole Nexium® tablets, orally, single dose administration	Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets Drug: Esomeprazole Nexium®
Experimental: Cohort 7: DWP14012 Amg DWP14012 Amg, tablets, orally, repeated dose administration(for 7days)	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 8: DWP14012 Bmg DWP14012 Bmg, tablets, orally, repeated dose administration(for 7days)	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Experimental: Cohort 9: DWP14012 Cmg DWP14012 Cmg, tablets, orally, repeated dose administration(for 7days)	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Placebo Comparator: Cohort 7-10: Placebo DWP14012 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 7days)	Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets
Active Comparator: Cohort 7-10: Esomeprazole Nexium®, orally, repeated dose administration(for 7days)	Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets Drug: Esomeprazole Nexium®
Experimental: Cohort 9: DWP14012 Dmg DWP14012 Dmg, tablets, orally, repeated dose administration(for 7days)	Drug: DWP14012 DWP14012 tablets Drug: Placebo DWP14012 placebo-matching tablets, Active control placebo-matching tablets

Outcome Measures

Primary Outcome Measures

Number and percentage of Participants With Adverse Events (AE) [Day -2(Randomization) to Day 11~18(Post-study visit)]
All AE standardized using MedDRA was assessed by investigator using the protocol defined grading system. Intensity was categorized as mild, moderate adn severe.
Number and percentage of Participants With Adverse Drug Reactions (ADR) [Day -2(Randomization) to Day 11~18(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 11~18(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 11~18(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 11~18(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 Outcome Measures

Cmax: Maximum concentration of DWP14012 [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in single ascending dose cohort
Cmax,ss: Maximum concentration of DWP14012 at steady state [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24h, Day 3-6 pre-dose, Day 7 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in multiple ascending dose cohort
Cmin,ss: Minimum concentration of DWP14012 at steady state [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24h, Day 3-6 pre-dose, Day 7 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in multiple ascending dose cohort
Tmax: Time of maximum concentration [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in single ascending dose cohort
Tmax,ss: Time of maximum concentration at steady state [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24h, Day 3-6 pre-dose, Day 7 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in multiple ascending dose cohort
AUClast: Area under the plasma concentration-time curve from time 0 to 48hours [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in single ascending dose cohort
AUCinf: Area under the plasma concentration-time curve from time 0 to infinity [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in single ascending dose cohort
AUCtau: Area under the plasma concentration-time curve from time 0 to tau(dosing interval) [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24h, Day 3-6 pre-dose, Day 7 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in multiple ascending dose cohort
T1/2: Elimination half-life [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in single ascending dose cohort
T1/2: Elimination half-life [0(pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24h, Day 3-6 pre-dose, Day 7 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours]
in multiple ascending dose cohort
Percentage of total time that the intragastric pH was above 4 [Day 1]
After single administration of the investigational products, 24hr gastric pH monitoring started.
Percentage of total time that the intragastric pH was above 4 [Day 7]
After multiple administration of the investigational products, 24hr gastric pH monitoring started.
Serum gastrin concentration profile [Day -2(Randomization) to Day 11~18(Post-study visit)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy adult males aged between 19 and 50 at screening
Those whose weight is between 55 and 90 kg and BMI is between 18.0 and 27.0
Those who are adequate to be subjects in this study upon judgment of the investigator after physical examination, clinical laboratory test, examination by interview, etc

Exclusion Criteria:

Those who have clinical significant liver, kidney, nervous system, respiratory, endocrine, hematology and oncology, cardiovascular, urinary, and mental diseases or past history
Those who have gastrointestinal diseases or past history of gastrointestinal diseases (gastrointestinal ulcer, gastritis, gastrospasm, gastroesophageal reflux, Crohn's disease etc.) that may affect safety and pharmacokinetic/pharmacodynamic evaluation of study drug, and those who have past history of gastrointestinal surgery (however, except simple appendectomy and herniotomy)
Those who have been Helicobacter pylori positive
Those whose plasma AST (SGOT) and ALT (SGPT) exceed 1.5 times to the upper limit of the normal range in screening including additional examinations prior to randomization
Those who have anatomical disability in insertion and maintenance of pH meter catheter

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

Daewoong Pharmaceutical Co. LTD.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Daewoong Pharmaceutical Co. LTD.

ClinicalTrials.gov Identifier:

NCT02757144

Other Study ID Numbers:

DW_DWP14012001

First Posted:

Apr 29, 2016

Last Update Posted:

Apr 25, 2017

Last Verified:

Apr 1, 2017

Additional relevant MeSH terms:

Esomeprazole

Study Results

No Results Posted as of Apr 25, 2017