Effect of Tegoprazan or RAPA114 on Pharmacokinetic of Atorvastatin in Healthy Adult Volunteers

An Open-label, Randomized, Multiple-dose, Replicated Crossover Study to Evaluate Drug-drug Interaction Following Co-administration of Tegoprazan or RAPA114 With Atorvastatin in Healthy Adults

This study aims to evaluate the influence of tegoprazan or RAPA114 on the Pharmacokinetic characteristics of atorvastatin following co-administration of tegoprazan or RAPA114 in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tegoprazan 50 mg; Drug: Atorvastatin 40 mg; Drug: RAPA114

Detailed Description

[Pharmacokinetic Assessments] : Blood concentration of atorvastatin, 2-OH atorvastatin

• Primary outcome: AUCτ, Css,max of atorvastatin
• Secondary outcome: Tss,max of atorvastatin, AUCτ, Css,max of 2-OH atorvastatin, metabolic ratio

[Sefety Assessments]

: Safety assessments with adverse event monitoring including subjective/objective symptoms, physical examination, vital signs, electrocardiogram, and laboratory test

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male adults aged 19 to 55 years (inclusive) at the time of his consent.
• Body mass index (BMI) ≥ 19.0 and ≤ 27.0 kg/m2 at screening.
• Decides to participate voluntarily in the trial after being fully informed of and understanding the study completely, and provides the written informed consent to participate in the trial and to comply with the trial-specific requirements.
• Has the ability and willingness to participate in the entire period of clinical trial.

Exclusion Criteria:

• A subject with clinically significant disease or history of hepatobiliary, renal, gastrointestinal, cardiovascular, musculoskeletal, endocrine, respiratory, neuropsychiatry or hemato-oncologic system, etc.
• A subject with a history of hypersensitivity reactions to main constituents of or identical affiliation of the investigational products (ex, HMG-CoA reductase inhibitor, gastric acid suppressants), or have allergic diseases that require treatment.
• A subject with a history of genetic myopathy or family history.
• A subject who has participated in other clinical trials and received the investigational products within 180 days prior to the randomization.
• A subject who received any medications or foods that could significantly affect the absorption, distribution, metabolism, or excretion of an investigational product within 30 days prior to the randomization.
• A subject with history of whole blood donation within 60 days, or with blood components or received transfusion within 30 days prior to the randomization.
• A subject with continued consumption of alcohol more than 140 g per week.
• A subject with AST, ALT, or γ-GT levels exceeding 1.5 times of the upper limit of the reference range in the screening test.
• A subject with a calculated glomerular filtration rate of less than 60 mL / min / 1.73 m2 in the screening test.
• A subject with any positive result on serology tests for hepatitis B, hepatitis C, HIV or syphilis in the screening test.
• A subject with galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose malabsorption, etc.
• Male subject who don't have willing to accept medically acceptable contraceptive methods during the course of clinical trial, or who plan to provide sperm.
• A subject who is determined to be ineligible to participate in the clinical trial by the investigator for other reasons.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Atorvastatin 40 mg; Oral administration of Atorvastatin 40 mg tablet once daily for 7 days	Drug: Atorvastatin 40 mg; Atorvastatin 40 mg; Other Names: Lipitor
Experimental: Atorvastatin 40 mg + Tegoprazan 50 mg; Oral administration of Atorvastatin 40 mg tablet and Tegoprazan 50 mg tablet once daily for 7 days	Drug: Tegoprazan 50 mg; Tegoprazan 50 mg tablet; Other Names: K-CAB; Drug: Atorvastatin 40 mg; Atorvastatin 40 mg; Other Names: Lipitor
Active Comparator: Atorvastatin 40 mg + RAPA114; Oral administration of Atorvastatin 40 mg tablet and RAPA114 tablet once daily for 7 days	Drug: Atorvastatin 40 mg; Atorvastatin 40 mg; Other Names: Lipitor; Drug: RAPA114; RAPA114 tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCτ of atorvastatin	Area under the plasma drug concentration-time curve at steady state	Pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in each period
Css,max of atorvastatin	Maximum concentration of drug in plasma of atorvastatin at steady state	Pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tss,max of atorvastatin	Time to Cmax at steady state	Pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in each period
AUCτ of 2-OH atorvastatin	Area under the plasma drug concentration-time curve at steady state	Pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in each period
Css,max of 2-OH atorvastatin	Maximum concentration of drug in plasma of 2-OH atorvastatin at steady state	Pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in each period
metabolic ratio	AUCτ of 2-OH atorvastatin / AUCτ of atorvastatin	Pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in each period

Collaborators and Investigators

• Sponsor: HK inno.N Corporation
• Investigators: Principal Investigator: Jung-ryul Kim, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): April 20, 2020

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 29, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IN_APA_114

Drug and device information, study documents

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