Drug-drug Interactions and Safety Among JP-1366, Amoxicillin, and Clarithromycin in Healthy Volunteers

A Randomized, Open-label, Multiple-dose, 3-way Crossover Phase 1 Clinical Trial to Evaluate Drug-drug Interactions and Safety Among JP-1366, Amoxicillin, and Clarithromycin in Healthy Volunteers

To evaluate the effect of coadministration of amoxicillin and clarithromycin on safety, tolerability and pharmacokinetics of JP-1366 in healthy subjects and the effect of JP-1366 on safety, tolerability and pharmacokinetics of amoxicillin and clarithromycin in healthy subjects

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Associated Gastrointestinal Disease
• Intervention / Treatment: Drug: JP-1366 20mg 1capsule; Drug: Amoxicillin 500Mg Cap; Drug: Clarithromycin 500Mg Tab

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • CHA University Bundang Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject who has fully informed about this study and understand completely, decide to participate voluntarily and agree with the written consent approved by the IRB in Bundang Cha hospital before screening test.
• A healthy volunteer in the age of upper 19 at the time of the screening test.

• Subject whose BMI was 18.0 or more and 30.0 or less and whose body weight was 50kg or more if in male, and 45kg or more if in female at the same time.

  • Body Mass Index (BMI) = Body weight(kg) / Height(m)2

Exclusion Criteria:

1. Medical History

1. The Subject who has clinically significant diseases with liver, kidney, nervous system, digestive system, respiratory system, and endocrine system, musculoskeletal system or the blood or tumor disease, cardiovascular disease (including orthostatic hypotension), mental disorder or with history of the disease.
2. The subject who has a history of gastrointestinal disorders (gastrointestinal ulcers, gastritis, gastric ulcer, gastroesophageal reflux disease, Crohn's disease, etc.) or history of gastrointestinal surgery that may affect the safety and PK/PD Evaluation of the investigational product (Except for simple cecal surgery and hernia surgery)
3. The subject who has a hereditary disorder (galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption etc.).

2. Allergy drug hypersensitivity and drug abuse

1. The subject with clinically significant hypersensitivity reactions (Except a slight allergic rhinitis which is no need to administration).
2. The subject with the history of hypersensitivity reactions to the investigational product, the ingredients in investigational product (FCF, Sunset Yellow FCF), Digestive ulcer drugs and other drugs (aspirin, antibiotics, etc.)
3. The subject who has a history of drug abuse or who has tested positive for an abuse drug in a drug screening test.

3. Laboratory Test

1. Vital Sign Measures of resting blood pressure while the subject remained in the sitting position for at least 3 minutes. Systolic > 150 mmHg or < 90 mmHg, or diastolic > 100 mmHg or < 50 mmHg.

2. Screening laboratory test showing any of the following abnormal laboratory results:

   - ALT, AST, Total bilirubin > 2.0 x ULN

   • e-GFR < 60 mL/min/1.73m2 (CKD-EPI formula)
   • Positive result for Serological test (HBsAg, HCV Ab, HIV Ab, Syphilis regain test)
3. Clinically significant ECG abnormalities

4. Prohibited medication and therapy

1. The subject taking drug of enzyme induction or inhibition within one month prior to the first scheduled drug administration.
2. The subject who has participated in other clinical trials or bioequivalence studied and received and received clinical trial drug or bioequivalence study drug, within 6 months prior to the first scheduled drug administration.
3. The subject taking any prohibited drug or herbal medicine, OTC drugs or vitamin within 2 weeks prior to the first scheduled drug administration.
4. The subject who has taken any diet which affect to drug metabolism (Grapefruit juice, Broccoli, Garlic extract etc.) within 3 days prior to the first scheduled drug administration or who cannot be forbidden the ingestion of it.

5. Donating and Receiving blood

1. The subject who did a whole blood donation within 2 months prior to the first scheduled drug administration or a component blood donation (pheresis) within one month
2. The subject who has received blood transfusions within one month prior to the first scheduled drug administration.

6. Pregnant and Contraception

1. Pregnant and Lactating women
2. Subjects who do not agree to use medically acceptable methods of contraception during the period study - Use of an intrauterine device - Use of barrier contraception (for men or women) and using spermicidal at the same time - Vasectomy, tubectomy, tubal ligation, hysterectomy

7. And others

1. Subjects who are judged unsuitable to participate in the study in the opinion of the investigator
2. The subject who continue to drink (over 21units/week, 1 unit = 10g of pure alcohol) within 6 months from screening or who cannot abstain from drinking during the clinical trial period from 3days before the first administration date.
3. The subject whose average smoking amount exceeds 10 cigarettes per day within 6 months.

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: Sequence A; T1→Washout period(D6~14)→ T3→Washout period(D20~28)→ T2; T1: JP-1366 1capsule, 2 times per 1 day, repetition administration for 5 days; T2: amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days; T3: JP-1366 1 capsule + amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days	Drug: JP-1366 20mg 1capsule; will be orally administered; Drug: Amoxicillin 500Mg Cap; Amoxicilin 500Mg 2 capsules will be orally administered; Drug: Clarithromycin 500Mg Tab; Amoxicilin 500Mg 1 tablet will be orally administered
Experimental: Sequence B; T1 →Washout period(D6~14)→ T2→Washout period(D20~28) → T3; T1: JP-1366 1 capsule, 2 times per 1 day, repetition administration for 5 days; T2: amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days; T3: JP-1366 1 capsule + amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days	Drug: JP-1366 20mg 1capsule; will be orally administered; Drug: Amoxicillin 500Mg Cap; Amoxicilin 500Mg 2 capsules will be orally administered; Drug: Clarithromycin 500Mg Tab; Amoxicilin 500Mg 1 tablet will be orally administered
Experimental: Sequence C; T2 →Washout period(D6~14)→ T3→Washout period(D20~28) → T1; T1: JP-1366 1capsule, 2 times per 1 day, repetition administration for 5 days; T2: amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days; T3: JP-1366 1 capsule + amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days	Drug: JP-1366 20mg 1capsule; will be orally administered; Drug: Amoxicillin 500Mg Cap; Amoxicilin 500Mg 2 capsules will be orally administered; Drug: Clarithromycin 500Mg Tab; Amoxicilin 500Mg 1 tablet will be orally administered
Experimental: Sequence D; T2 →Washout period(D6~14)→ T1→Washout period(D20~28) → T3; T1: JP-1366 1 capsule, 2 times per 1 day, repetition administration for 5 days; T2: amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days; T3: JP-1366 1 capsule + amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days	Drug: JP-1366 20mg 1capsule; will be orally administered; Drug: Amoxicillin 500Mg Cap; Amoxicilin 500Mg 2 capsules will be orally administered; Drug: Clarithromycin 500Mg Tab; Amoxicilin 500Mg 1 tablet will be orally administered
Experimental: Sequence E; T3 →Washout period(D6~14)→ T1→Washout period(D20~28) → T2; T1: JP-1366 1 capsule, 2 times per 1 day, repetition administration for 5 days; T2: amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days; T3: JP-1366 1 capsule + amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days	Drug: JP-1366 20mg 1capsule; will be orally administered; Drug: Amoxicillin 500Mg Cap; Amoxicilin 500Mg 2 capsules will be orally administered; Drug: Clarithromycin 500Mg Tab; Amoxicilin 500Mg 1 tablet will be orally administered
Experimental: Sequence F; T3 →Washout period(D6~14)→ T2→Washout period(D20~28) → T1; T1: JP-1366 1 capsule, 2 times per 1 day, repetition administration for 5 days; T2: amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days; T3: JP-1366 1 capsule + amoxicillin 500mg 2 capsules + clarithromycin 500mg 1 tablet, 2 times per 1 day, repetition administration for 5 days	Drug: JP-1366 20mg 1capsule; will be orally administered; Drug: Amoxicillin 500Mg Cap; Amoxicilin 500Mg 2 capsules will be orally administered; Drug: Clarithromycin 500Mg Tab; Amoxicilin 500Mg 1 tablet will be orally administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax,ss of JP-1366, Amoxicillin, Clarithromycin	The time of steady state (after repetition administration for 5 days)
AUCτ of JP-1366, Amoxicillin, Clarithromycin	The time of steady state (after repetition administration for 5 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Tmax of JP-1366, Amoxicillin, Clarithromycin, 14-OH-Clarithromycin	The time of steady state (after repetition administration for 5 days)
t1/2 of JP-1366, Amoxicillin, Clarithromycin, 14-OH-Clarithromycin	The time of steady state (after repetition administration for 5 days)
CLss/F of JP-1366, Amoxicillin, Clarithromycin, 14-OH-Clarithromycin	The time of steady state (after repetition administration for 5 days)
Vdss/F of JP-1366, Amoxicillin, Clarithromycin, 14-OH-Clarithromycin	The time of steady state (after repetition administration for 5 days)
Cmax,ss of 14-OH-Clarithromycin	The time of steady state (after repetition administration for 5 days)
AUCτ of 14-OH-Clarithromycin	The time of steady state (after repetition administration for 5 days)
14-OH-Clarithromycin/Clarithromycin metabolic ratio	The time of steady state (after repetition administration for 5 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Vital sign, Physical examination, Laboratory test, 12-lead ECG, Prior/ Concomitant medication, Adverse event.	Through study completion, an average of 46 days

Collaborators and Investigators

• Sponsor: Onconic Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Actual): January 16, 2021
• Study Completion (Actual): January 19, 2021

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 3, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Amoxicillin; Clarithromycin
• Other Study ID Numbers: JP-1366-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No