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

• Conditions: Efavirenz; Penicilliosis; Pharmacokinetics
• Interventions: Other: Pharmacokinetic study

• Registration Number: NCT04031053
• Lead Sponsor: Chiang Mai University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-04
• Study First Submitted: 2019-04-25
• Study Start: 2019-06-01
• Study First Submitted QC: 2019-07-22
• Last Update Submitted: 2019-07-22
• Study First Posted: 2019-07-24
• Last Update Posted: 2019-07-24
• Primary Completion: 2021-04-30
• Study Completion: 2021-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intensive Pharmacokinetic Group	Pharmacokinetic study	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.
Trough Level Group	Pharmacokinetic study	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.

Primary Outcome Measures

Name	Time	Method
Itraconazole and its metabolites level	45 days	Itraconazole and its metabolite level will be measured to create drug level curve (before and after exposed to efavirenz)

Trial Locations

Locations (1)

Chiang Mai University Hospital; 🇹🇭 Chiang Mai, Thailand