Study to Evaluate Effects of Food or Proton Pump Inhibitor on the Pharmacokinetics of Itraconazole in Healthy Volunteers

Achlorhydria Clinical Trial

Official title:

An Open-label, Three-period, One-sequence Crossover Clinical Trial to Evaluate the Effects of Food or Proton Pump Inhibitor on the Pharmacokinetics of Itraconazole in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04942652
• Other study ID #: Itraconazole_pH
• Status: Completed
• Phase: Phase 1
• Start date: July 13, 2021
• Est. completion date: August 24, 2021

Study information

• Verified date: September 2021
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the effects of food or proton pump inhibitor on the pharmacokinetics of itraconazole in healthy volunteers.

Description:

Evaluation criteria - Pharmacokinetic assessment with plasma concentrations of itraconazole and hydroxy-itraconazole - Safety assessments with adverse event monitoring including subjective/objective symptoms, physical examination, vital signs, and laboratory tests

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: August 24, 2021
• Est. primary completion date: August 6, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy adult aged = 19 years and = 50 years at the time of screening
• Body weight of = 55.0 kg and = 90.0 kg, with body mass index (BMI) of = 19.0 kg/m2 and = 30.0 kg/m2 at the time of screening
• A subject without any congenital or chronic disease, and has no medical examination result as pathological symptoms or signs
• A subject who listened to sufficient explanation and fully understood this study, and voluntarily decided to participate and agreed in writing to comply with the precautions
• A subject determined eligible for this study by investigator based physical examination, clinical laboratory tests, interview, etc.

Exclusion Criteria:

• A subject with clinically significant hepatobiliary (severe hepatic impairment, etc.), renal (severe renal impairment, etc.), neurologic, immunologic, respiratory, gastrointestinal, endocrine, blood•oncology, cardiovascular (heart failure, Torsades de pointes, etc.), urinary, or, psychical diseases (except for simple dental past history such as tartar, impacted tooth, or wisdom tooth) or a history
• A subject who has hypersensitivity to the investigational products, drugs containing the same class, or other drugs (penicillin and antibiotics, etc.), or a history of clinically significant hypersensitivity
• A subject with a history of gastrointestinal disorders (gastrointestinal ulcer, gastritis, gastrospasm, gastroesophageal reflux disease, Crohn's disease, etc.) or surgery (except for simple appendectomy and herniotomy) that may affect the safety and pharmacokinetics of the investigational products
• A subject with the following results in the screening test:

1. Blood AST (GOT), ALT (GPT): > Normal range upper × 1.5

2. QTc interval: > 450 ms

3. Positive serological test (syphilis test, hepatitis B test, hepatitis C test, human immunodeficiency virus (HIV) test)

• A subject with systolic blood pressure < 80 mmHg or > 160 mmHg, or diastolic blood pressure < 50 mmHg or > 100 mmHg when vital signs are measured in sitting position after resting for at least 3 minutes
• A subject with a history of drug abuse
• A subject who administered any prescription drugs or herbal medicine within 2 weeks prior to the expected date of the first dose, or any over-the-counter drug (OTC drug, health functional food or vitamin within 1 week prior to the expected date of the first dose (However, can participate in the study if otherwise decided eligible by the investigator), or is expected to administer it
• A subject who administered drugs that induce (such as barbitals) or inhibit (such as clarithromycin) the drug metabolizing enzymes within 1 month prior to the expected date of the first dose
• A subject who participated in other clinical trial or bioequivalence study within 6 months prior to the expected date of the first dose
• A subject who donated whole blood within 2 months or the component blood within 1 month prior to the expected date of the first dose, or received blood transfusion within 1 month prior to the expected date of the first dose
• A subject with persistent alcohol intake (> 21 units/week, 1 unit = 10 g of pure alcohol), or inability to abstain from drinking from 3 days before the expected date of the first dose until the last discharge
• A subject with inability to refrain from grapefruit-containing food from 3 days before the expected date of the first dose until the last discharge
• A subject with excessive caffeine intake (> 5 units/day), or inability to refrain from caffeine or caffeine-containing food from 3 days before the expected date of the first dose until the last discharge
• A subject with inability to use a medically acceptable double contraception or contraception throughout the study and for at least 4 weeks after the last dose, and with inability to agree to donate sperm until the period

Related Conditions & MeSH terms

• Achlorhydria

Intervention

Drug:
• Itraconazole 200 mg
Itraconazole 100 mg capsule x 2
• Esomeprazole 40 mg
Esomeprazole 40 mg tablet x 1

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul	Jongno-gu

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	AUClast of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	AUCinf of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	Tmax of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	t1/2 of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	CL/F of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	Vd/F of itraconazole	Pharmacokinetic parameters of itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	Cmax of hydroxy-itraconazole	Pharmacokinetic parameters of hydroxy-itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	AUClast of hydroxy-itraconazole	Pharmacokinetic parameters of hydroxy-itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	AUCinf of hydroxy-itraconazole	Pharmacokinetic parameters of hydroxy-itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	Tmax of hydroxy-itraconazole	Pharmacokinetic parameters of hydroxy-itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	t1/2 of hydroxy-itraconazole	Pharmacokinetic parameters of hydroxy-itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose
Primary	metabolic ratio of hydroxy-itraconazole	Pharmacokinetic parameters of hydroxy-itraconazole	Day 1/Day 8/Day 16 pre-dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 hour post-dose