To Investigate PK and PD of CJ-12420, Clarithromycin, Amoxicillin After Multiple Dose Administration

An Open-label, Randomized Study to Evaluate Pharmacokinetic Interaction, Pharmacodynamics and Safety After Multiple Oral Dosing of CJ-12420 and Amoxicillin/Clarithromycin in Healthy Subjects

Cohort 1

To evaluate the pharmacokinetic interactions of CJ-12420 after multiple oral doses of CJ-12420 given alone or in combination with amoxicillin/clarithromycin in healthy subjects.

Cohort 2

To evaluate the pharmacodynamic profiles of CJ-12420 after multiple oral doses of CJ-12420 in combination with amoxicillin/clarithromycin in healthy subjects as compared to an active control group, i.e., pantoprazole in combination with amoxicillin/clarithromycin.

Study Overview

• Status: Completed
• Conditions: Drug Interaction; Pharmacokinetic; Pharmacodynamic
• Intervention / Treatment: Drug: CJ-12420 100mg; Drug: CLR 500mg; Drug: CJ-12420 50mg; Drug: AMX 1g; Drug: Pantoprazole 40mg

Detailed Description

To evaluate the pharmacokinetic the drug-drug interaction of CJ-12420 and amoxicillin/clarithromycin and investigate the pharmacodynamic of co-administration of CJ-12420 and amoxicillin and clarithromycin.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Inje University Busan Baik Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male volunteers aged ≥19 and ≤45 years at screening;
2. No congenital or chronic disease, and no morbid symptoms or findings on screening tests;
3. Body mass index (BMI) ≥18.5 and ≤28 kg/m2;
4. Considered eligible based on medical examinations (including interview, vital signs, 12-lead ECG, physical exam and laboratory tests) which are set and performed in accordance with the nature of investigational product by the investigator;
5. Voluntary consent to participate in the study after being fully informed of purpose and procedures of the study, and profiles of investigational product prior to the participation;
6. For Cohort 2, positive on 13C urea breath test.

Exclusion Criteria:

1. Medical history

   1. History or current evidence for diseases considered clinically relevant by the investigator including hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrine, neurologic, hemato-oncological, urinary, or cardiovascular (including cardiac arrhythmia) diseases;
   2. History of gastrointestinal diseases (such as gastritis, gastrodynia, gastroesophageal reflux disease, Crohn's disease and ulcer) or abdominal surgery (except for simple appendectomy or herniotomy) which are considered to have potential effect on drug absorption by the investigator;
   3. For Cohort 2, previous treatment failure for H. pylori eradication.

2. Laboratory tests and ECG

   1. AST or ALT ≥ 1.25 x upper limit of normal (ULN);
   2. Total bilirubin ≥ 1.5 x ULN;
   3. eGFR calculated by CKD-EPI formula < 80 mL/min;
   4. Any clinically relevant ECG abnormalities.

3. Allergy and drug abuse

   1. History of hypersensitivity to drugs containing investigational products (penicillins, cephems, macrolides, pantoprazole and benzimidazole) and other drugs (including aspirin and antibiotics);
   2. History of drug abuse or positive on drug screening test.

4. Drug/dietary restrictions

   1. Medications (including herbal supplements) or abnormal diet (e.g., grapefruit juice > 1 L/day, excessive garlic, broccoli, kale, etc.) which may have effect on absorption, distribution, metabolism and excretion of investigational products within 28 days prior to the first study dose;
   2. Use of prescription drugs, over-the-counter drugs (OTCs) or vitamins within 10 days prior to the first study dose;
   3. Participating in other study and receive investigational product within 3 months prior to the first study dose.

5. Blood donation and transfusion

   1. Whole blood donation within 60 days prior to the first study dose;
   2. Donation of blood components or transfusion within 30 days prior to the first study dose.

6. Pregnancy and contraception

   1. Pregnant or breast-feeding;
   2. Subject or his partner's inability to use of medically qualifying dual-contraceptive methods or medically acceptable contraception (including intrauterine device with established pregnancy failure rate, barrier methods with spermicide, vasectomy, tubectomy, tubal ligation and hysterectomy) from screening to 30 days of the last dose of investigational product.

7. Others

   1. Heavy use of alcohol (average alcohol intake ≥30 g/day) or positive on alcohol test;
   2. Heavy smoker (>10 cigarettes/day);
   3. Caffeine intake > 400 mg/day;
   4. Any clinically relevant findings considered inappropriate for study participation at the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CJ-12420 100mg; CJ-12420 100mg BID for 5 days	Drug: CJ-12420 100mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days
Experimental: CJ-12420 50mg + CLR 500mg + AMX 1g; coadministration of CJ-12420 50mg and CLR 500mg/AMX 1g BID for 7 days	Drug: CLR 500mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Clarithromycin 500mg; Drug: CJ-12420 50mg; Cohort 2: bid for 7 days; Drug: AMX 1g; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Amoxicillin 1g
Active Comparator: Pantoprazole 40mg + CLR 500mg + AMX 1g; coadministration of Pantoprazole 40mg and CLR 500mg/AMX 1g BID for 7 days	Drug: CLR 500mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Clarithromycin 500mg; Drug: AMX 1g; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Amoxicillin 1g; Drug: Pantoprazole 40mg; Cohort 2: bid for 7 days
Experimental: CJ-12420 100mg + CLR 500mg + AMX 1g; coadministration of CJ-12420 100mg, CLR 500mg/AMX 1g BID for 7 days	Drug: CJ-12420 100mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Drug: CLR 500mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Clarithromycin 500mg; Drug: AMX 1g; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Amoxicillin 1g
Experimental: CLR 500mg/AMX 1g; CLR 500mg/AMX 1g BID for 5 days	Drug: CLR 500mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Clarithromycin 500mg; Drug: AMX 1g; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Amoxicillin 1g
Experimental: CJ-12420 100mg + CLR 500mg/AMX 1g; coadministration of CJ-12420 100mg and CLR 500mg/AMX 1g BID for 7 days	Drug: CJ-12420 100mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Drug: CLR 500mg; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Clarithromycin 500mg; Drug: AMX 1g; Cohort 1: bid for 5 days Cohort 2: bid for 7 days; Other Names: Amoxicillin 1g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax) of CJ-12420, clarithromycin and amoxicillin	Up to 120 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) of CJ-12420, clarithromycin and amoxicillin		Up to 120 hours
Time of maximum observed concentraion(tmax) of CJ-12420, clarithromycin and amoxicillin		Up to 120 hours
Half life(t1/2) of CJ-12420, clarithromycin and amoxicillin		Up to 120 hours
Oral clearance at steady state(CLss/F) of CJ-12420, clarithromycin and amoxicillin		Up to 120 hours
Apparent volume of distribution at steady state(Vdss/F) of CJ-12420, clarithromycin and amoxicillin		Up to 120 hours
median pH	Data from the pH probe monitoring	Up to 24 hours
Time at pH > 3 (%)	the percent of time the pH as data from the pH probe monitoring	Day -1, Day 1, Day 7 up to 24 hours
Time at pH > 4 (%)	the percent of time the pH as data from the pH probe monitoring	Day -1, Day 1, Day 7 up to 24 hours
Time at pH > 6 (%)	the percent of time the pH as data from the pH probe monitoring	Day -1, Day 1, Day 7 up to 24 hours

Collaborators and Investigators

• Sponsor: HK inno.N Corporation
• Investigators: Principal Investigator: Jae-Gook Shin, Inje University College of Medicine Busan Paik Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (Estimate): January 6, 2017

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

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; Amoxicillin; Clarithromycin; Pantoprazole
• Other Study ID Numbers: CJ_APA_107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided