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

NCT04942652 | Completed Phase 1

• 1 other identifier: Itraconazole_pH
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Achlorhydria

Outcome Measures

Primary Outcomes (13)

• 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

Study Arms (3)

Itraconazole 200 mg under fasted condition

EXPERIMENTAL

A single oral administration of itraconazole 200 mg under fasted condition

Drug: Itraconazole 200 mg

Itraconazole 200 mg under fed condition

EXPERIMENTAL

A single oral administration of itraconazole 200 mg under fed condition

Drug: Itraconazole 200 mg

Esomeprazole 40 mg + Itraconazole 200 mg under fasted condition

EXPERIMENTAL

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; Drug: Esomeprazole 40 mg

Interventions

Itraconazole 200 mg DRUG

Itraconazole 100 mg capsule x 2

Also known as: Sporanox capsule

Esomeprazole 40 mg + Itraconazole 200 mg under fasted condition; Itraconazole 200 mg under fasted condition; Itraconazole 200 mg under fed condition

Esomeprazole 40 mg DRUG

Esomeprazole 40 mg tablet x 1

Also known as: Nexium

Esomeprazole 40 mg + Itraconazole 200 mg under fasted condition

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Blood AST (GOT), ALT (GPT): \> Normal range upper × 1.5
• QTc interval: \> 450 ms
• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, Jongno-gu, 03080, South Korea

Location

MeSH Terms

Conditions

Achlorhydria

Interventions

Itraconazole; Esomeprazole

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• SeungHwan Lee, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 20, 2021
• First Posted: June 28, 2021
• Study Start: July 13, 2021
• Primary Completion: August 6, 2021
• Study Completion: August 24, 2021
• Last Updated: September 29, 2021

Record last verified: 2021-09

Locations

KR (1)