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
1
14
11.1
10.8

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
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

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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:

Study Results

No Results Posted as of Apr 25, 2017