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

• Sponsor: Daewoong Pharmaceutical Co. LTD. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03487562
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 7
• Actual Duration (Months): 9.1
• Patients Per Site Per Month: 5.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: DWP14012 Amg; Drug: DWP14012 Bmg; Drug: Clarithromycin; Drug: Amoxicillin; Drug: Lansoprazole	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: Apr 8, 2018
• Actual Primary Completion Date: Jan 11, 2019
• Actual Study Completion Date: Jan 11, 2019

Arms and Interventions

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: DWP14012 Bmg; DWP14012 Bmg; Drug: Clarithromycin; Clarithromycin 500 mg; Drug: Amoxicillin; Amoxicillin 1 g
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

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. Percentage of total time that the intragastric pH was above 4 [Period 1 Day -1 and Group A, C Day 7 0~24 hours]

   Part I

8. Percentage of total time that the intragastric pH was above 4 [Day -1, Day 1, Day 7 0~24 hours]

   Part II

9. Percentage of total time that the intragastric pH was above 6 [Period 1 day -1 and Group A, C Day 7 0~24 hours]

   Part I

10. Percentage of total time that the intragastric pH was above 6 [Day -1, Day 1, Day 7 0~24 hours]

    Part II

11. Serum gastrin concentration profile [Period 1 Day -1 and Group A, C Day 7 pre-dose, 2, 4, 6, 8, 12, 24, 48 hours]

    Part I

12. 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

13. 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

14. 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.

15. 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).

16. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Daewoong Pharmaceutical Co. LTD.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daewoong Pharmaceutical Co. LTD.
• ClinicalTrials.gov Identifier: NCT03487562
• Other Study ID Numbers: DW_DWP14012003
• First Posted: Apr 4, 2018
• Last Update Posted: Jun 26, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Amoxicillin; Clarithromycin; Lansoprazole; Dexlansoprazole

Study Results

No Results Posted as of Jun 26, 2019