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

Study Overview
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Brief Summary
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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

Official Title
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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
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Healthy

Intervention / Treatment
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* Drug: DWP14012 Amg
* Drug: DWP14012 Bmg
* Drug: Clarithromycin
* Drug: Amoxicillin
* Drug: Lansoprazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |