Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of After Administrations of DWP14012 Alone and Combinations of DWP14012, Clarithromycin and Amoxicillin in Healthy Male Subjects

A Randomized, Open-label, Multiple Dose, Two-part Phase I Clinical Trial to Compare the Pharmacokinetics, Pharmacodynamics and Safety/Tolerability of DWP14012 After Administrations of DWP14012 Alone and Combinations of DWP14012, Clarithromycin and Amoxicillin in Healthy Male Subjects

This is a randomized, open-label, multiple dose, two-part phase I clinical trial to compare the pharmacokinetics, pharmacodynamics and safety/tolerability of DWP14012 after administrations of DWP14012 alone and combinations of DWP14012, Clarithromycin and Amoxicillin in healthy male subjects

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: DWP14012 Amg; Drug: Clarithromycin; Drug: Amoxicillin; Drug: DWP14012 Bmg; Drug: Lansoprazole

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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
• Part I: Those who have been helicobacter pylori negative at screening Part II: Those who have been helicobacter pylori positive at screening
• 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 whose plasma AST (SGOT) and ALT (SGPT) exceed to the upper limit of the normal range
• Those who have anatomical disability in insertion and maintenance of pH meter catheter

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Part I: A-B-D-C A: DWP14012 A mg bid B: DWP14012 A mg bid + Clarithromycin 500 mg bid C: DWP14012 A mg bid + Clarithromycin 500 mg bid + Amoxicillin 1 g bid D: Clarithromycin 500 mg bid + Amoxicillin 1 g bid	Drug: DWP14012 Amg; DWP14012 Amg; Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g
Experimental: Sequence 2; Part I: B-C-A-D A: DWP14012 A mg bid B: DWP14012 A mg bid + Clarithromycin 500 mg bid C: DWP14012 A mg bid + Clarithromycin 500 mg bid + Amoxicillin 1 g bid D: Clarithromycin 500 mg bid + Amoxicillin 1 g bid	Drug: DWP14012 Amg; DWP14012 Amg; Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g
Experimental: Sequence 3; Part I: C-D-B-A A: DWP14012 A mg bid B: DWP14012 A mg bid + Clarithromycin 500 mg bid C: DWP14012 A mg bid + Clarithromycin 500 mg bid + Amoxicillin 1 g bid D: Clarithromycin 500 mg bid + Amoxicillin 1 g bid	Drug: DWP14012 Amg; DWP14012 Amg; Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g
Experimental: Sequence 4; Part I: D-A-C-B A: DWP14012 A mg bid B: DWP14012 A mg bid + Clarithromycin 500 mg bid C: DWP14012 A mg bid + Clarithromycin 500 mg bid + Amoxicillin 1 g bid D: Clarithromycin 500 mg bid + Amoxicillin 1 g bid	Drug: DWP14012 Amg; DWP14012 Amg; Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g
Experimental: A; Part II: (DWP14012 B mg + Clarithromycin 500 mg + Amoxicillin 1g) bid	Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g; Drug: DWP14012 Bmg; DWP14012 Bmg
Experimental: B; Part II: (DWP14012 A mg + Clarithromycin 500 mg + Amoxicillin 1g) bid	Drug: DWP14012 Amg; DWP14012 Amg; Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g
Experimental: C; Part II: (Lansoprazole 30 mg + Clarithromycin 500 mg + Amoxicillin 1g) bid	Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g; Drug: Lansoprazole; Lansoprazole 30 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax,ss: Maximum concentration of DWP14012, clarithromycin and metabolite and amoxicillin at steady state	Part I: each period (Group A, B, C, D) Part II: Group A, B	Day 1~7 pre-dose, Day 8 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours
Cmin,ss: Minimum concentration of DWP14012, clarithromycin and metabolite and amoxicillin at steady state	Part I: each period (Group A, B, C, D) Part II: Group A, B	Day 1~7 pre-dose, Day 8 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours
Cav,ss: Average concentration of DWP14012, clarithromycin and metabolite and amoxicillin at steady state	Part I: each period (Group A, B, C, D) Part II: Group A, B	Day 1~7 pre-dose, Day 8 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours
AUCt,ss: Area under the drug concentration-time curve within a dosing interval at steady states	Part I: each period (Group A, B, C, D) Part II: Group A, B	Day 1~7 pre-dose, Day 8 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours
Tmax,ss: Time of maximum concentration at steady state	Part I: each period (Group A, B, C, D) Part II: Group A, B	Day 1~7 pre-dose, Day 8 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours
T1/2: Elimination half-life	Part I: each period (Group A, B, C, D) Part II: Group A, B	Day 1~7 pre-dose, Day 8 pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours
Percentage of total time that the intragastric pH was above 4	Part I	Period 1 Day -1 and Group A, C Day 7 0~24 hours
Percentage of total time that the intragastric pH was above 4	Part II	Day -1, Day 1, Day 7 0~24 hours
Percentage of total time that the intragastric pH was above 6	Part I	Period 1 day -1 and Group A, C Day 7 0~24 hours
Percentage of total time that the intragastric pH was above 6	Part II	Day -1, Day 1, Day 7 0~24 hours
Serum gastrin concentration profile	Part I	Period 1 Day -1 and Group A, C Day 7 pre-dose, 2, 4, 6, 8, 12, 24, 48 hours
Serum gastrin concentration profile	Part II	Day -1 pre-dose, 2, 4, 6, 8, 12 hours, Day 1 and 7 pre-dose, 2, 4, 6, 8, 12, 24, 48 hours
Number 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 and severe	Day -2 (Randomization) to Day 60 (Post-study visit of Part I) and Day 42 (Follow up visit of Part II)
Number of Participants With Clinically Significant Vital Sign findings	Blood pressure(mmHg), pulse (beats/min) 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 60 (Post-study visit of Part I) and Day 42 (Follow up visit of Part II)
Number of Participants With Clinically Significant Electrocardiogram(12-lead ECG) findings	Ventricular rate(beats/min), RR, PR interval(msec), QRS duration(msec), 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 54~60 (Post-study visit of Part I) and Day 36~42 (Follow up visit of Part II)
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 60 (Post-study visit of Part I) and Day 42 (Follow up visit of Part II)

Collaborators and Investigators

• Sponsor: Daewoong Pharmaceutical Co. LTD.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2018
• Primary Completion (Actual): January 11, 2019
• Study Completion (Actual): January 11, 2019

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 4, 2018

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 25, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole; Amoxicillin; Clarithromycin
• Other Study ID Numbers: DW_DWP14012003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No