Itraconazole Oral Absorption

Prediction of Itraconazole Oral Absorption From In Vitro Dissolution

For tablets to be absorbed, the drug must dissolve after being swallowed. Drugs with low solubility sometimes require the inert ingredients in tablets to help the drug dissolve after being swallowed. This study uses itraconazole as an example drug with low solubility. Itraconazole tablets with different inert ingredients and manufacturing will be administered to healthy volunteers to see if the different inert ingredients and manufacturing impact drug absorption.

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: fast itraconazole tablet; Drug: medium itraconazole tablet; Drug: slow itraconazole tablet; Drug: oral itraconazole solution

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subject is healthy, as determined by screening evaluation that is not greater than 30 days before the first drug study visit
• Subject is male or female between 18 and 65 years of age inclusive.
• Subject is an acceptable candidate for venipuncture.
• Subject is willing to stop all non-routine OTC medications, as well as vitamins, dietary supplements, and herbals, for 24 hours prior to study drug administration and during pharmacokinetic study visits.
• Subject is willing, for each of the four drug study periods, to stop consuming grapefruit, grapefruit products, star fruit, star fruit products, Seville oranges, and St. John's wort from 72-hour before study drug administration until the period's last blood sample
• Subject is willing to not smoke (or use e-cigarettes) during study visits.

Exclusion Criteria:

• Subject has a significant medical disease (including cardiovascular, pulmonary, hematologic, endocrine, immunologic, neurologic, gastrointestinal or psychiatric).
• Subject shows evidence of congestive heart failure or history of congestive heart failure.
• Subject exhibits electrocardiogram (12 lead) with clinically significant abnormalities (e.g. QTcF >450 msec).
• Subject has a history of alcohol or drug abuse, which in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in this trial.
• Subject is pregnant, breast feeding, or trying to become pregnant.
• Female subject of childbearing potential is unwilling or unable to use a medically acceptable method of contraception throughout the entire study period and for one week after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or her partner are: oral birth control pill, condom with spermicide, diaphragm with spermicide, IUD, vaginal spermicidal suppository, surgical sterilization of patient or their partner(s), abstinence, or hormonal-based patches, ring, injections, and implants.
• Subject routinely uses (i.e. daily or weekly) prescription medication except hormonal birth control medication, routinely uses (i.e. daily or weekly) OTC medication, or routinely uses (i.e. daily or weekly) St. John's Wort. OTC medications do not include vitamins, dietary supplements, or herbals.
• Subject routinely uses (i.e. daily or weekly) acid blockers, antacids, anti-diarrhea, stimulants, appetite suppressants, or anti-nausea medication or other drugs that modulate GI functio
• Subject is currently taking itraconazole or medication known to interact with itraconazole.
• Subject is allergic to itraconazole.
• Subject has liver impairment as assessed by alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels greater than the upper limit of normal (ULN).
• Subject has renal impairment as assessed by creatinine clearance lower than 50mL/min/1.73m2, using the CKD-EPI formula.
• Subject is not willing or able to be adherent to study protocol (e.g. study visits).
• Subject has a condition in which in the opinion of the PI or medical physician would increase risk to the subject or interfere with the integrity of the study.
• Subject has received an investigational product within 30 days prior to study drug administration, plans to receive an investigational product during their study participation period, or plans to donate blood to any other clinical trial during their study participation period.
• Subject has provided plasma donation within 1 month of screening or any blood donation/loss more than 500 mL within 8 weeks prior to study drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A (fast, medium, oral solution, then slow); Participants first receive fast tablet, then medium tablet, then oral solution, and then slow tablet. Washout period is (at least) one week.	Drug: fast itraconazole tablet; 100mg dose; Other Names: fast dissolving itraconazole tablet; Drug: medium itraconazole tablet; 100mg dose; Other Names: medium dissolving itraconazole tablet; Drug: slow itraconazole tablet; 100mg dose; Other Names: slow dissolving itraconazole tablet; Drug: oral itraconazole solution; 100mg dose; Other Names: commercial oral itraconazole solution
Experimental: Sequence B (medium, slow, fast, then oral solution); Participants first receive medium tablet, then slow tablet, then fast tablet, and then oral solution. Washout period is (at least) one week.	Drug: fast itraconazole tablet; 100mg dose; Other Names: fast dissolving itraconazole tablet; Drug: medium itraconazole tablet; 100mg dose; Other Names: medium dissolving itraconazole tablet; Drug: slow itraconazole tablet; 100mg dose; Other Names: slow dissolving itraconazole tablet; Drug: oral itraconazole solution; 100mg dose; Other Names: commercial oral itraconazole solution
Experimental: Sequence C (slow, oral solution, medium, then fast); 3, 4, 2, 1 Participants first receive slow tablet, then oral solution, then medium tablet, then fast tablet. Washout period is (at least) one week.	Drug: fast itraconazole tablet; 100mg dose; Other Names: fast dissolving itraconazole tablet; Drug: medium itraconazole tablet; 100mg dose; Other Names: medium dissolving itraconazole tablet; Drug: slow itraconazole tablet; 100mg dose; Other Names: slow dissolving itraconazole tablet; Drug: oral itraconazole solution; 100mg dose; Other Names: commercial oral itraconazole solution
Experimental: Sequence D (oral solution, fast, slow, then medium); Participants first receive oral solution, fast tablet, then slow tablet, and then medium tablet. Washout period is (at least) one week.	Drug: fast itraconazole tablet; 100mg dose; Other Names: fast dissolving itraconazole tablet; Drug: medium itraconazole tablet; 100mg dose; Other Names: medium dissolving itraconazole tablet; Drug: slow itraconazole tablet; 100mg dose; Other Names: slow dissolving itraconazole tablet; Drug: oral itraconazole solution; 100mg dose; Other Names: commercial oral itraconazole solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	area under the curve from 0-72hr	0-72hr

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximum concentration during the time interval	0-72hr

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Actual): May 21, 2022
• Study Completion (Actual): May 21, 2022

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Pharmaceutical Solutions; Itraconazole; Hydroxyitraconazole
• Other Study ID Numbers: HP-00084585

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No