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

NCT03487562 | Completed Phase 1

• 1 other identifier: DW_DWP14012003
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (16)

• 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)

Study Arms (7)

Sequence 1

EXPERIMENTAL

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; Drug: Clarithromycin; Drug: Amoxicillin

Sequence 2

EXPERIMENTAL

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; Drug: Clarithromycin; Drug: Amoxicillin

Sequence 3

EXPERIMENTAL

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; Drug: Clarithromycin; Drug: Amoxicillin

Sequence 4

EXPERIMENTAL

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; Drug: Clarithromycin; Drug: Amoxicillin

A

EXPERIMENTAL

Part II: (DWP14012 B mg + Clarithromycin 500 mg + Amoxicillin 1g) bid

Drug: DWP14012 Bmg; Drug: Clarithromycin; Drug: Amoxicillin

B

EXPERIMENTAL

Part II: (DWP14012 A mg + Clarithromycin 500 mg + Amoxicillin 1g) bid

Drug: DWP14012 Amg; Drug: Clarithromycin; Drug: Amoxicillin

C

EXPERIMENTAL

Part II: (Lansoprazole 30 mg + Clarithromycin 500 mg + Amoxicillin 1g) bid

Drug: Clarithromycin; Drug: Amoxicillin; Drug: Lansoprazole

Interventions

DWP14012 Amg DRUG

DWP14012 Amg

B; Sequence 1; Sequence 2; Sequence 3; Sequence 4

DWP14012 Bmg DRUG

DWP14012 Bmg

A

Clarithromycin DRUG

Clarithromycin 500 mg

A; B; C; Sequence 1; Sequence 2; Sequence 3; Sequence 4

Amoxicillin DRUG

Amoxicillin 1 g

A; B; C; Sequence 1; Sequence 2; Sequence 3; Sequence 4

Lansoprazole DRUG

Lansoprazole 30 mg

C

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daewoong Pharmaceutical Co. LTD.: lead

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Interventions

Clarithromycin; Amoxicillin; Lansoprazole

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2018
• First Posted: April 4, 2018
• Study Start: April 8, 2018
• Primary Completion: January 11, 2019
• Study Completion: January 11, 2019
• Last Updated: June 26, 2019

Record last verified: 2019-06

Locations

KR (1)