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

Study Overview
=================
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.

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

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: DWP14012
* Drug: Placebo
* Drug: Esomeprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 adn severe. | Day -2(Randomization) to Day 11 18(Post-study visit) | 
| 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 11 18(Post-study visit) | 
| 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 11 18(Post-study visit) | 
| 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 11 18(Post-study visit) | 
| 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 11 18(Post-study visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum concentration of DWP14012 | in single ascending dose cohort | 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 | 
| Cmax,ss: Maximum concentration of DWP14012 at steady state | in multiple ascending dose cohort | 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 | 
| Cmin,ss: Minimum concentration of DWP14012 at steady state | in multiple ascending dose cohort | 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 | 
| Tmax: Time of maximum concentration | in single ascending dose cohort | 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 | 
| Tmax,ss: Time of maximum concentration at steady state | in multiple ascending dose cohort | 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 | 
| AUClast: Area under the plasma concentration-time curve from time 0 to 48hours | in single ascending dose cohort | 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 | 
| AUCinf: Area under the plasma concentration-time curve from time 0 to infinity | in single ascending dose cohort | 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 | 
| AUCtau: Area under the plasma concentration-time curve from time 0 to tau(dosing interval) | in multiple ascending dose cohort | 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 | 
| T1/2: Elimination half-life | in single ascending dose cohort | 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 | 
| T1/2: Elimination half-life | in multiple ascending dose cohort | 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 | 
| Percentage of total time that the intragastric pH was above 4 | After single administration of the investigational products, 24hr gastric pH monitoring started. | Day 1 | 
| Percentage of total time that the intragastric pH was above 4 | After multiple administration of the investigational products, 24hr gastric pH monitoring started. | Day 7 | 
| Serum gastrin concentration profile |  | Day -2(Randomization) to Day 11 18(Post-study visit) |