Itraconazole Pharmacokinetic With and Without Efavirenz Using the Capsule Formulation as Part of Talaromycosis Treatment in HIV-infected Adults (ITRAPK)

Assessment of Itraconazole Pharmacokinetic With and Without Efavirenz Using the Capsule Formulation as Part of Talaromycosis Treatment in HIV-infected Adults

Talaromycosis continues to be a common opportunistic fungal infection among people living with HIV/AIDS (PLWHA) in Southeast Asia and remains a leading cause of death among this population. Itraconazole (ITZ) is an important component of talaromycosis treatment. In Thailand, the capsule formulation of ITZ is primarily used to treat talaromycosis but it is known to have lower bioavailability than the more expensive solution formulation. Limited data on the drug exposure of ITZ with the capsule formulation are available in adults PLWHA in Thailand. Moreover, the effect of efavirenz (EFV), which has been recommended as the first line antiretroviral therapy in Thailand, to ITZ level is not well understood. Thus, our aim is to assess ITZ pharmacokinetics with and without EFV in adult PLWHA receiving talaromycosis treatment with the capsule formulation. An understanding of the relationship between ITZ drug exposure and its active metabolite (hydroxyl-itraconazole) and treatment response is also planned to help optimize therapy.

Study Overview

• Status: Unknown
• Conditions: Pharmacokinetics; Efavirenz; Penicilliosis
• Intervention / Treatment: Other: Pharmacokinetic study

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Thailand
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-infected participant who has an evidence of T. marneffei invasive infection will be enrolled to the study.

Description

Inclusion Criteria:

1. 18 years or older
2. Available documentation of HIV infection
3. ITZ capsule therapy is indicated for talaromycosis infection with the anticipation to start on EFV-based ART
4. Willing to consent and compliance to the study protocol

Exclusion Criteria:

1. History of ITZ allergy
2. Pregnancy or lactation
3. Use concurrent medication that could interfere with ITZ level
4. Creatinine clearance less than 30 mL/min
5. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) value is more than 5 times of upper normal limit and total bilirubin is more than 3 times above upper normal limit
6. Hemoglobin less than 7 mg/dL
7. History of ITZ exposure within 35 days (only applicable to intense PK group)

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intensive Pharmacokinetic Group; After receiving the first dose of ITZ, a single blood sample will be collected 12-hours post-dose. On Day 7, the blood will be collected for intensive PK study. After 7 days of combined ITZ + EFV, a blood sample will be collected immediately (e.g. within 30 minutes) prior to administering the next ITZ dose. An identical set of intensive PK blood samples will be drawn 2 weeks after initiating the EFV based regimen.	Other: Pharmacokinetic study; The blood will be collected at pre-dose and at 1, 3, 4, 5, 6, 8 and 12-hour post dose
Trough Level Group; On Days 7 and 14, a single blood sample will be collected immediately (e.g. within 30 minutes) prior to administering the next ITZ dose. After initiating an EFV based regimen, a single blood sample will be collected immediately (e.g. within 30 minutes) prior to administering the next ITZ dose on Days 7 and 14.	Other: Pharmacokinetic study; The blood will be collected at pre-dose and at 1, 3, 4, 5, 6, 8 and 12-hour post dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Itraconazole and its metabolites level	Itraconazole and its metabolite level will be measured to create drug level curve (before and after exposed to efavirenz)	45 days

Collaborators and Investigators

• Sponsor: Chiang Mai University
• Collaborators: Thailand Research Fund
• Investigators: Principal Investigator: Quanhathai Kaewpoowat, MD, Chiang Mai University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Anticipated): April 30, 2021
• Study Completion (Anticipated): April 30, 2021

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Efavirenz; Penicilliosis
• Other Study ID Numbers: ITRAPK

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