Clinical trial NCT02998437: Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Clarithromycin, Amoxicillin and Ilaprazole
Official title: A Randomized, Open-label, Parallel-design Study to Evaluate Pharmacokinetic Drug Interactions and Safety After Coadministration of Clarithromycin, Amoxicillin and Ilaprazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction Potentiation
Lead sponsor: Il-Yang Pharm. Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Severance Hospital
First posted: 2016-12-20
Enrollment: 28
Sex: MALE
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluate the pharmacokinetic drug interaction in Ilaprazole, Clarithromycin, Amoxicillin.

Detailed description: This study evaluate the pharmacokinetic drug interaction and safety in Ilaprazole, Clarithromycin, Amoxicillin.

Eligibility criteria: Inclusion Criteria:

1. Healthy male adults aged ≥19 years and \<50 years at screening
2. Body mass index ≥18.5 and \<25

   * Body mass index (kg/m2) = body weight (kg)/\[height (m)\]2
3. Men who have sexual relationship with women of child bearing potential must give consent to using contraceptive measures (condoms, spermicide, and menstrual cycle control) and avoiding sperm donation during the study and up to 28 days following the last dose of IMP (these contraceptive measures are not required if the male subject or female partner is infertile).
4. Those who voluntarily decided to participate in this study and gave written consent to comply with the requirements after receiving sufficient explanation and fully understanding this study.

Exclusion Criteria:

1. Hypersensitivity or history of clinically significant hypersensitivity to active ingredients or excipients (in particular, Yellow No. 4 (Tartrazine); Yellow No. 5 (Sunset Yellow FCF); macrolide antibiotics such as Clarithromycin and erythromycin; or Penicillins)
2. History of QT prolongation or ventricular arrhythmia (including Torsadedes de pointes)
3. Clinically significant, current or past disorder of hepatobiliary (severe hepatic impairment, etc.), renal (severe renal impairment, etc.), nervous, immune, respiratory, endocrine, blood•tumor, cardiovascular (heart failure, etc.), or psychiatric system
4. History of gastrointestinal disorder (Crohn's disease, ulcer, etc.) or operation (excluding simple appendectomy or herniotomy) that may affect drug absorption
5. Administration of other IMP from other study (including biological comparability test) within 3 months of the first dose of IMP.
6. Whole blood donation within 60 days, or apheresis donation within 30 days before the first dose of IMP.
7. Constant caffeine intake (\> 5 cups of coffee/day, \> 1250 cc of tea/day, \> 1250 cc of cola/day), constant smoking (more than 10 cigarettes/day) or constant alcohol drinking (more than 210 g/week) or inability to refrain from alcohol consumption from 2 days before the first dose of IMP until the end of PK assessment.
8. Consumption of grapefruit-containing food within 7 days before the first dose of IMP
9. History of drug abuse within 1 year before screening, or positive response in urine drug misuse/abuse screening test
10. Use of medicinal products that are expected to or may affect the metabolism of IMP; St. John's wort; or relevant preparations within 30 days of IMP administration
11. Use of following medicinal products within given time period excluding local preparations, which do not have significant systemic absorption, and hormonal contraceptives

    * Prescription drug within 14 days of the first dose of IMP
    * OTC including health supplements and vitamins within 7 days of the first dose of IMP
    * Medicinal products via depot injection or other implantations within 30 days of the first dose of IMP (excluding contraceptives)
    * Drug metabolizing enzyme inducer or inhibitor such as barbiturate within 30 days before the first dose of IMP
12. Stable vital sign measured in sitting position at screening: systolic blood pressure \> 150 mmHg or \< 90 mmHg, diastolic blood pressure \> 100 mmHg or \< 50 mmHg, pulse rate \> 110 bpm or \<40 bpm
13. Following findings at screening

    * Blood total bilirubin \> 1.5 x upper limit of normal
    * Blood AST (SGOT), ALT (SGPT) \> 1.25 x upper limit of normal
    * MDRD-estimated eGFR \< 60 mL/min/1.73m2 eGFR (estimated glomerular filtration rate)(mL/min/1.73m2) = 175 x \[serum creatinine (mg/dL)\]-1.154 x \[age (years)\]-0.203
    * Positive serum test (hepatitis B, hepatitis C, HIV, syphilis)
14. Those considered ineligible by the investigator due to other screening results or reasons.

Primary outcomes:
measure: Ilaprazole AUClast(Area Under the plasma concentration-time Curve at the last observed time point)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole Cmax(the maximum serum concentration)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin AUClast
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin Cmax
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
Secondary outcomes:
measure: Ilaprazole AUCinf(Area Under the plasma concentration-time Curve from time zero to infinity)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole Tmax(the time to reach Cmax)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole t1/2(the elimination half-life)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole CL/F(the oral clearance)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Ilaprazole Vd/F(apparent volume of distribution after non-intravenous administration)
timeFrame: Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin AUCinf
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin Tmax
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin t1/2
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin CL/F
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
measure: Clarithromycin, Amoxicillin Vd/F
timeFrame: Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Severance Hospital
name: Min MS Park, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jin BH, Yoo BW, Park J, Kim JH, Lee JY, Shin JS, Park MS. Pharmacokinetic drug interaction and safety after coadministration of clarithromycin, amoxicillin, and ilaprazole: a randomised, open-label, one-way crossover, two parallel sequences study. Eur J Clin Pharmacol. 2018 Sep;74(9):1149-1157. doi: 10.1007/s00228-018-2489-2. Epub 2018 May 30.