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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- Number of Participants With Clinically Significant Vital Sign findings
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 19 Years to 50 Years (Adult)
- Sex
- 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
Arms & Interventions
Cohort 4: DWP14012 Dmg
DWP14012 Dmg, tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 1: DWP14012 Amg
DWP14012 Amg, tablets, orally, single dose administration
Intervention: DWP14012 (Drug)
Cohort 1: DWP14012 Amg
DWP14012 Amg, tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 2: DWP14012 Bmg
DWP14012 Bmg, tablets, orally, single dose administration
Intervention: DWP14012 (Drug)
Cohort 2: DWP14012 Bmg
DWP14012 Bmg, tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 3: DWP14012 Cmg
DWP14012 Cmg, tablets, orally, single dose administration
Intervention: DWP14012 (Drug)
Cohort 3: DWP14012 Cmg
DWP14012 Cmg, tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 4: DWP14012 Dmg
DWP14012 Dmg, tablets, orally, single dose administration
Intervention: DWP14012 (Drug)
Cohort 5: DWP14012 Emg
DWP14012 Emg, tablets, orally, single dose administration
Intervention: DWP14012 (Drug)
Cohort 5: DWP14012 Emg
DWP14012 Emg, tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 6: DWP14012 Fmg
DWP14012 Emg, tablets, orally, single dose administration
Intervention: DWP14012 (Drug)
Cohort 6: DWP14012 Fmg
DWP14012 Emg, tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 1-6: Placebo
DWP14012 placebo-matching tablets, Active-control placebo-matching tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 1-6: Esomeprazole
Nexium® tablets, orally, single dose administration
Intervention: Placebo (Drug)
Cohort 1-6: Esomeprazole
Nexium® tablets, orally, single dose administration
Intervention: Esomeprazole (Drug)
Cohort 7: DWP14012 Amg
DWP14012 Amg, tablets, orally, repeated dose administration(for 7days)
Intervention: DWP14012 (Drug)
Cohort 7: DWP14012 Amg
DWP14012 Amg, tablets, orally, repeated dose administration(for 7days)
Intervention: Placebo (Drug)
Cohort 8: DWP14012 Bmg
DWP14012 Bmg, tablets, orally, repeated dose administration(for 7days)
Intervention: DWP14012 (Drug)
Cohort 8: DWP14012 Bmg
DWP14012 Bmg, tablets, orally, repeated dose administration(for 7days)
Intervention: Placebo (Drug)
Cohort 9: DWP14012 Cmg
DWP14012 Cmg, tablets, orally, repeated dose administration(for 7days)
Intervention: DWP14012 (Drug)
Cohort 9: DWP14012 Cmg
DWP14012 Cmg, tablets, orally, repeated dose administration(for 7days)
Intervention: Placebo (Drug)
Cohort 7-10: Placebo
DWP14012 placebo-matching tablets, Active-control placebo-matching tablets, orally, repeated dose administration(for 7days)
Intervention: Placebo (Drug)
Cohort 7-10: Esomeprazole
Nexium®, orally, repeated dose administration(for 7days)
Intervention: Placebo (Drug)
Cohort 7-10: Esomeprazole
Nexium®, orally, repeated dose administration(for 7days)
Intervention: Esomeprazole (Drug)
Cohort 9: DWP14012 Dmg
DWP14012 Dmg, tablets, orally, repeated dose administration(for 7days)
Intervention: DWP14012 (Drug)
Cohort 9: DWP14012 Dmg
DWP14012 Dmg, tablets, orally, repeated dose administration(for 7days)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of Participants With Clinically Significant Vital Sign findings
Time Frame: 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 and percentage of Participants With Adverse Drug Reactions (ADR)
Time Frame: 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 Electrocardiogram(12-lead ECG) findings
Time Frame: 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
Time Frame: 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)
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Percentage of total time that the intragastric pH was above 4(Day 7)