Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Naproxen, Aceclofenac, Celecoxib and Ilaprazole

Drug Interaction Potentiation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05237297
• Other study ID #: IL49NS01
• Status: Completed
• Phase: Phase 1
• Start date: February 17, 2022
• Est. completion date: July 27, 2022

Study information

• Verified date: June 2023
• Source: Il-Yang Pharm. Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: July 27, 2022
• Est. primary completion date: July 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 55 Years

Eligibility

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. Those with genetic problems such as galactose intolerance, Lap lactase deficiency, or glucose-galactose malabsorption.

9. 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.

10. A person who has a history of drug abuse or has tested positive in a urine drug screening test within one year of screening.

11. 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.

12. 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.

13. 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.

14. 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).

15. 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.

16. A person who received a blood transfusion within 30 days prior to the first administration date of the clinical trial drug.

17. Pregnant or lactating women.

18. A person who determines that the tester is inappropriate to participate in clinical trials due to other reasons.

Related Conditions & MeSH terms

• Drug Interaction Potentiation

Intervention

Drug:
• Ilaprazole
Ilaprazole 10mg
• Naproxen
Naproxen 500mg
• Aceclofenac
Aceclofenac 100mg
• Celecoxib
Celecoxib 200mg

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Il-Yang Pharm. Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1	ilaprazole, naproxen 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
Primary	Part 1	ilaprazole, naproxen 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
Primary	Part 2	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
Primary	Part 2	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
Primary	Part 3	ilaprazole, celecoxib Cmax,ss(Maximum concentration of drug in plasma at steady state)	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Primary	Part 3	ilaprazole, celecoxib AUCtau,ss(Area under the plasma drug concentration-time curve within a dosing interval (tau) at steady state)	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 1.	ilaprazole, naproxen 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
Secondary	Part 1.	ilaprazole, naproxen 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
Secondary	Part 1.	ilaprazole, naproxen 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
Secondary	Part 1.	ilaprazole, naproxen 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
Secondary	Part 1.	ilaprazole, naproxen fluctuation	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 2.	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
Secondary	Part 2.	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
Secondary	Part 2.	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
Secondary	Part 2.	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
Secondary	Part 2.	ilaprazole, aceclofenac fluctuation	Predose(0hour), after dose 0.5hour, 0.75hour, 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 3.	ilaprazole, celecoxib Tmax,ss(Time to maximum plasma concentration at steady state)	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 3.	ilaprazole, celecoxib CLss/F(Apparent clearance of drug in plasma at steady state)	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 3.	ilaprazole, celecoxib Vdss/F(Apparent volume of distribution at steady state)	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 3.	ilaprazole, celecoxib Cmin,ss(Minimum concentration of drug in plasma at steady state)	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours
Secondary	Part 3.	ilaprazole, celecoxib fluctuation	Predose(0hour), after dose 1hour, 1.5hours, 2hours, 2.5hours, 3hours, 3.5hours, 4hours, 5hours, 6hours, 8hours, 10hours, 12hours