Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Ilaprazole and Aceclofenac

A Randomized, Open-label, Multiple-dose, Crossover Clinical Trial to Investigate the Pharmacokinetic Drug Interactions and Safety After Co-administration of Ilaprazole and Aceclofenac in Healthy Adults

This study evaluate the pharmacokinetic drug interactions and safety after co-administration of ilaprazole and Aceclofenac in healthy adults.

Study Overview

• Status: Completed
• Conditions: Drug Interaction Potentiation
• Intervention / Treatment: Drug: Ilaprazole; Drug: Aceclofenac

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy adults aged 19 or older and 55 or younger at the time of screening tests.
2. Men weigh more than 55 kg and women weigh more than 50 kg.

3. Those who have a body mass index of 18.5 kg/m2 or more and less than 27.0 kg/m2.

   ※ Body mass index (kg/m2) = Weight (kg)/[Height (m)]2

4. If participants are a woman, participants must apply to one of the following.

   • Menopausal (no natural menstruation for at least 2 years)
   • Surgical infertility (autonomous exudation or bilateral ovarian resection, intubation ligation, or other infertility)
5. Men who have sexual relationship with women of child bearing potential must give consent to using contraceptive measures(condoms, spermicide, and menstrual cycle control) for at least 28 days after the final administration of clinical trial and clinical drugs (if the male test subject or female partner is infertile, the above contraception is unnecessary).
6. A person who has heard sufficient explanation of this clinical trial and fully understood it, voluntarily decided to participate, and agreed in writing to comply with precautions.

Exclusion Criteria:

1. A person with a history of mental illness or illness corresponding to clinically significant hepatobiliary tract (hepatic liver disorder, kidney (severe renal disorder, etc.), nervous system, immune system, respiratory system (bronchial asthma, etc.), urinary system, digestive system, endocrine blood and tumor, cardiovascular system (severe high blood pressure, heart failure, etc.).
2. Active peptic ulcer/bleeding or a person with a medical history.
3. A person who tends to bleed or have a blood clotting disorder.
4. Patients with a history of gastrointestinal bleeding or perforation due to NSAID treatment in the past.
5. Those with a history of gastrointestinal diseases (Crohn's disease, ulcerative colitis, etc.) or surgery (except for simple appendectomy or hernia surgery) that can affect the absorption of drugs.
6. Person with a history of significant drug hypersensitivity reactions to the ingredients and additives of clinical trial drugs. In particular, NSAIDs and aspirin such as Yellow No. 4 (Tartrazine), Yellow No. 5 (Sunset Yellow FCF), sulfonamide, ilaprazole and naproxen, aceclofenac, celecoxib, diclofenac, etc.
7. A person with a history of asthma, rhinitis, and nasal polyps due to aspirin or other NSAIDs (including COX-2 inhibitors).

8. A person who was judged to be inappropriate as a test subject in a screening test conducted within 28 days before the first administration date of the clinical trial drug.

   • In the case of > 1.25 times the upper limit of AST and ALT normal range in the blood,
   • When the potassium concentration in the blood exceeds 5.5 mEq/L,
   • Estimated Global Film Rate (eGFR) <60 mL/min/1.73 m2 using the Modification of Diet in Regular Disease (MDRD) formula
   • Immunology and serology tests (hepatitis B test, hepatitis C test, human immunodeficiency virus (HIV) test, syphilis test) result are positive factors.
   • After resting for more than 5 minutes, systolic blood pressure >150 mmHg or << in vital signs measured at the seat> Those who showed values corresponding to 90 mmHg, dilator blood pressure >100 mmHg, or <50 mmHg.
9. A person who has a history of drug abuse or has tested positive in a urine drug screening test within one year of screening.

10. If the tester determines that the following drugs, excluding topical drugs without significant systemic absorption, may affect this test or affect the safety of the test subject within the relevant period,

    • In the case of taking a prescription drug or herbal medicine within 14 days prior to the first administration date of the clinical trial drug,
    • In the case of taking general medicines including health foods and vitamin preparations within 7 days prior to the first administration of clinical trial drugs,
    • A person who took drugs such as barbital drugs and other drugs inducing and inhibiting drugs within 30 days prior to the first administration of clinical trial drugs.
11. A person who continuously smoked excessively or consumed caffeine or alcohol (caffeine: >5 cups/day, alcohol: >210 g/week, tobacco: >10 g/day) or who cannot stop smoking, caffeine and alcohol consumption during each hospitalization period.
12. A person who has consumed grapefruit-containing food within 7 days prior to the first administration date of clinical trial drugs or cannot be prohibited from taking it during the clinical trial period.
13. A person who participated in another clinical trial within 180 days prior to the first administration date of the clinical trial drug and received the clinical trial drug (in the case of biological agents, it may be based on an extended period considering a half-life).
14. A person who donated whole blood within 60 days prior to the first administration date of clinical trial drugs or donated component blood within 30 days.
15. A person who received a blood transfusion within 30 days prior to the first administration date of the clinical trial drug.
16. Pregnant or lactating women.
17. A person who determines that the tester is inappropriate to participate in clinical trials due to 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ilaprazole & aceclofenac 1; Period 1 : Ilaprazole 10mg/tab, one a day, 5 days Period 2 : aceclofenac 100mg/tab, twice a day, 4 days and aceclofenac 100mg/tab, one a day one at the 5 day Period 3 : Ilaprazole 10mg/tab, one a day, 5 days + aceclofenac 100mg/tab, twice a day, 5 days	Drug: Ilaprazole; Ilaprazole 10mg; Other Names: Noltec(the brand name); Drug: Aceclofenac; Aceclofenac 100mg; Other Names: Airtal(the brand name)
Experimental: ilaprazole & aceclofenac 2; Period 1 : Ilaprazole 10mg/tab, one a day, 5 days + aceclofenac 100mg/tab, twice a day, 5 days Period 2 : Ilaprazole 10mg/tab, one a day, 5 days Period 3 : aceclofenac 100mg/tab, twice a day, 4 days and aceclofenac 100mg/tab, one a day one at the 5 day	Drug: Ilaprazole; Ilaprazole 10mg; Other Names: Noltec(the brand name); Drug: Aceclofenac; Aceclofenac 100mg; Other Names: Airtal(the brand name)
Experimental: ilaprazole & aceclofenac 3; Period 1 : aceclofenac 100mg/tab, twice a day, 4 days and aceclofenac 100mg/tab, one a day one at the 5 day Period 2 : Period 3 : Ilaprazole 10mg/tab, one a day, 5 days + aceclofenac 100mg/tab, twice a day, 5 days Period 3 : Ilaprazole 10mg/tab, one a day, 5 days	Drug: Ilaprazole; Ilaprazole 10mg; Other Names: Noltec(the brand name); Drug: Aceclofenac; Aceclofenac 100mg; Other Names: Airtal(the brand name)
Experimental: ilaprazole & aceclofenac 4; Period 1 : Ilaprazole 10mg/tab, one a day, 5 days Period 2 : Ilaprazole 10mg/tab, one a day, 5 days + aceclofenac 100mg/tab, twice a day, 5 days Period 3 : aceclofenac 100mg/tab, twice a day, 4 days and aceclofenac 100mg/tab, one a day one at the 5 day	Drug: Ilaprazole; Ilaprazole 10mg; Other Names: Noltec(the brand name); Drug: Aceclofenac; Aceclofenac 100mg; Other Names: Airtal(the brand name)
Experimental: ilaprazole & aceclofenac 5; Period 1 : Ilaprazole 10mg/tab, one a day, 5 days + aceclofenac 100mg/tab, twice a day, 5 days Period 2 : aceclofenac 100mg/tab, twice a day, 4 days and aceclofenac 100mg/tab, one a day one at the 5 day Period 3 : Ilaprazole 10mg/tab, one a day, 5 days	Drug: Ilaprazole; Ilaprazole 10mg; Other Names: Noltec(the brand name); Drug: Aceclofenac; Aceclofenac 100mg; Other Names: Airtal(the brand name)
Experimental: ilaprazole & aceclofenac 6; Period 1 : aceclofenac 100mg/tab, twice a day, 4 days and aceclofenac 100mg/tab, one a day one at the 5 day Period 2 : Ilaprazole 10mg/tab, one a day, 5 days Period 3 : Ilaprazole 10mg/tab, one a day, 5 days + aceclofenac 100mg/tab, twice a day, 5 days	Drug: Ilaprazole; Ilaprazole 10mg; Other Names: Noltec(the brand name); Drug: Aceclofenac; Aceclofenac 100mg; Other Names: Airtal(the brand name)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ilaprazole, aceclofenac Cmax,ss	Maximum concentration of drug in plasma at steady state	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
ilaprazole, aceclofenac AUCtau,ss	Area under the plasma drug concentration-time curve within a dosing interval (tau) at steady state	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ilaprazole, aceclofenac Tmax,ss	Time to maximum plasma concentration at steady state	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
ilaprazole, aceclofenac CLss/F	Apparent clearance of drug in plasma at steady state	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
ilaprazole, aceclofenac Vdss/F	Apparent volume of distribution at steady state	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
ilaprazole, aceclofenac Cmin,ss	Minimum concentration of drug in plasma at steady state	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
ilaprazole, aceclofenac fluctuation	fluctuation	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours

Collaborators and Investigators

• Sponsor: Il-Yang Pharm. Co., Ltd.
• Investigators: Principal Investigator: Minsoo Park, PhD, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Aceclofenac
• Other Study ID Numbers: REIL49NS01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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