Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of After Administrations of DWP14012 Alone and Combinations of DWP14012, Clarithromycin and Amoxicillin in Healthy Male Subjects
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT03487562
- Lead Sponsor
- Daewoong Pharmaceutical Co. LTD.
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 48
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sequence 1 Clarithromycin 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 B DWP14012 Amg Part II: (DWP14012 A mg + Clarithromycin 500 mg + Amoxicillin 1g) bid Sequence 1 DWP14012 Amg 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 Sequence 2 DWP14012 Amg 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 Sequence 3 DWP14012 Amg 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 A DWP14012 Bmg Part II: (DWP14012 B mg + Clarithromycin 500 mg + Amoxicillin 1g) bid Sequence 1 Amoxicillin 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 C Clarithromycin Part II: (Lansoprazole 30 mg + Clarithromycin 500 mg + Amoxicillin 1g) bid C Amoxicillin Part II: (Lansoprazole 30 mg + Clarithromycin 500 mg + Amoxicillin 1g) bid Sequence 3 Clarithromycin 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 Sequence 4 DWP14012 Amg 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 Sequence 4 Amoxicillin 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 C Lansoprazole Part II: (Lansoprazole 30 mg + Clarithromycin 500 mg + Amoxicillin 1g) bid Sequence 2 Clarithromycin 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 Sequence 2 Amoxicillin 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 Sequence 3 Amoxicillin 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 Sequence 4 Clarithromycin 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 A Amoxicillin Part II: (DWP14012 B mg + Clarithromycin 500 mg + Amoxicillin 1g) bid A Clarithromycin Part II: (DWP14012 B mg + Clarithromycin 500 mg + Amoxicillin 1g) bid B Clarithromycin Part II: (DWP14012 A mg + Clarithromycin 500 mg + Amoxicillin 1g) bid B Amoxicillin Part II: (DWP14012 A mg + Clarithromycin 500 mg + Amoxicillin 1g) bid
- Primary Outcome Measures
Name Time Method AUCt,ss: Area under the drug concentration-time curve within a dosing interval at steady states 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 Part I: each period (Group A, B, C, D) Part II: Group A, B
Cav,ss: Average concentration of DWP14012, clarithromycin and metabolite and amoxicillin at steady state 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 Part I: each period (Group A, B, C, D) Part II: Group A, B
T1/2: Elimination half-life 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 Part I: each period (Group A, B, C, D) Part II: Group A, B
Number of Participants With Clinically Significant Vital Sign findings Day -2 (Randomization) to Day 60 (Post-study visit of Part I) and Day 42 (Follow up visit of Part II) 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.
Cmin,ss: Minimum concentration of DWP14012, clarithromycin and metabolite and amoxicillin at steady state 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 Part I: each period (Group A, B, C, D) Part II: Group A, B
Number of Participants With Clinically Significant Laboratory results Day -2 (Randomization) to Day 60 (Post-study visit of Part I) and Day 42 (Follow up visit of Part II) Hematology, Blood chemistry, Coagulation and Urinalysis were tested. The Average, Median, Standard Deviation, Min, Max values will be calculated to assess the safety/tolerability.
Cmax,ss: Maximum concentration of DWP14012, clarithromycin and metabolite and amoxicillin at steady state 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 Part I: each period (Group A, B, C, D) Part II: Group A, B
Percentage of total time that the intragastric pH was above 6 Day -1, Day 1, Day 7 0~24 hours Part II
Serum gastrin concentration profile Day -1 pre-dose, 2, 4, 6, 8, 12 hours, Day 1 and 7 pre-dose, 2, 4, 6, 8, 12, 24, 48 hours Part II
Number of Participants With Clinically Significant Electrocardiogram(12-lead ECG) findings Day -2 (Randomization) to Day 54~60 (Post-study visit of Part I) and Day 36~42 (Follow up visit of Part II) 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).
Tmax,ss: Time of maximum concentration at steady state 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 Part I: each period (Group A, B, C, D) Part II: Group A, B
Percentage of total time that the intragastric pH was above 4 Day -1, Day 1, Day 7 0~24 hours Part II
Number of participants with Adverse Events (AE) Day -2 (Randomization) to Day 60 (Post-study visit of Part I) and Day 42 (Follow up visit of Part II) All AE standardized using MedDRA was assessed by investigator using the protocol defined grading system. Intensity was categorized as mild, moderate and severe
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of