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

Daewoong Pharmaceutical Co. LTD.120 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

120

Conditions

Healthy

Interventions

DWP14012DRUG

DWP14012 tablets

PlaceboDRUG

DWP14012 placebo-matching tablets, Active control placebo-matching tablets

EsomeprazoleDRUG

Nexium®

Eligibility

Sex: MALEMin age: 19 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Seoul National University Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: Day -2(Randomization) to Day 11~18(Post-study visit)

Secondary Outcomes

Cmax: Maximum concentration of DWP14012

in single ascending dose cohort

Data from ClinicalTrials.gov

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Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: Day 7

Serum gastrin concentration profile

Time frame: Day -2(Randomization) to Day 11~18(Post-study visit)