Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DWP14012 After Oral Administration in Healthy Male Volunteers
- Registration Number
- NCT02757144
- Lead Sponsor
- Daewoong Pharmaceutical Co. LTD.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 120
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 9: DWP14012 Dmg DWP14012 DWP14012 Dmg, tablets, orally, repeated dose administration(for 7days) Cohort 4: DWP14012 Dmg Placebo DWP14012 Dmg, tablets, orally, single dose administration Cohort 6: DWP14012 Fmg DWP14012 DWP14012 Emg, tablets, orally, single dose administration Cohort 5: DWP14012 Emg Placebo DWP14012 Emg, tablets, orally, single dose administration Cohort 6: DWP14012 Fmg Placebo DWP14012 Emg, tablets, orally, single dose administration Cohort 7: DWP14012 Amg Placebo DWP14012 Amg, tablets, orally, repeated dose administration(for 7days) Cohort 8: DWP14012 Bmg DWP14012 DWP14012 Bmg, tablets, orally, repeated dose administration(for 7days) Cohort 1: DWP14012 Amg Placebo DWP14012 Amg, tablets, orally, single dose administration Cohort 2: DWP14012 Bmg Placebo DWP14012 Bmg, tablets, orally, single dose administration Cohort 9: DWP14012 Cmg Placebo DWP14012 Cmg, tablets, orally, repeated dose administration(for 7days) Cohort 7-10: Placebo Placebo DWP14012 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 7days) Cohort 7-10: Esomeprazole Placebo Nexium®, orally, repeated dose administration(for 7days) Cohort 9: DWP14012 Dmg Placebo DWP14012 Dmg, tablets, orally, repeated dose administration(for 7days) Cohort 1: DWP14012 Amg DWP14012 DWP14012 Amg, tablets, orally, single dose administration Cohort 2: DWP14012 Bmg DWP14012 DWP14012 Bmg, tablets, orally, single dose administration Cohort 3: DWP14012 Cmg Placebo DWP14012 Cmg, tablets, orally, single dose administration Cohort 5: DWP14012 Emg DWP14012 DWP14012 Emg, tablets, orally, single dose administration Cohort 1-6: Placebo Placebo DWP14012 placebo-matching tablets, Active-control placebo-matching tablets, orally, single dose administration Cohort 1-6: Esomeprazole Placebo Nexium® tablets, orally, single dose administration Cohort 8: DWP14012 Bmg Placebo DWP14012 Bmg, tablets, orally, repeated dose administration(for 7days) Cohort 9: DWP14012 Cmg DWP14012 DWP14012 Cmg, tablets, orally, repeated dose administration(for 7days) Cohort 7: DWP14012 Amg DWP14012 DWP14012 Amg, tablets, orally, repeated dose administration(for 7days) Cohort 3: DWP14012 Cmg DWP14012 DWP14012 Cmg, tablets, orally, single dose administration Cohort 4: DWP14012 Dmg DWP14012 DWP14012 Dmg, tablets, orally, single dose administration Cohort 1-6: Esomeprazole Esomeprazole Nexium® tablets, orally, single dose administration Cohort 7-10: Esomeprazole Esomeprazole Nexium®, orally, repeated dose administration(for 7days)
- Primary Outcome Measures
Name Time Method 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 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 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.
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.
- Secondary Outcome Measures
Name Time Method 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
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
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
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
Serum gastrin concentration profile Day -2(Randomization) to Day 11~18(Post-study visit) 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
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
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
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
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.
Trial Locations
- Locations (1)
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of