Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DWP14012 After Oral Administration in Healthy Male Volunteers
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
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
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.- DW_DWP14012001