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

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

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

Study Overview

• Status: Completed
• Conditions: Achlorhydria
• Intervention / Treatment: Drug: Itraconazole 200 mg; Drug: Esomeprazole 40 mg

Detailed 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

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jongno-gu
    • Seoul, Jongno-gu, Korea, Republic of, 03080
      • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole 200 mg under fasted condition; A single oral administration of itraconazole 200 mg under fasted condition	Drug: Itraconazole 200 mg; Itraconazole 100 mg capsule x 2; Other Names: Sporanox capsule
Experimental: Itraconazole 200 mg under fed condition; A single oral administration of itraconazole 200 mg under fed condition	Drug: Itraconazole 200 mg; Itraconazole 100 mg capsule x 2; Other Names: Sporanox capsule
Experimental: Esomeprazole 40 mg + Itraconazole 200 mg under fasted condition; Oral administration of esomeprazole 40 mg once daily for 6 days and then a single oral administration of itraconazole 200 mg under fasted condition	Drug: Itraconazole 200 mg; Itraconazole 100 mg capsule x 2; Other Names: Sporanox capsule; Drug: Esomeprazole 40 mg; Esomeprazole 40 mg tablet x 1; Other Names: Nexium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: SeungHwan Lee, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): August 6, 2021
• Study Completion (Actual): August 24, 2021

Study Registration Dates

• First Submitted: June 20, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Stomach Diseases; Acid-Base Imbalance; Achlorhydria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Esomeprazole
• Other Study ID Numbers: Itraconazole_pH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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