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Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole (MSG15)

Primary Purpose

Invasive Fungal Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SUBA itraconazole
Conventional itraconazole
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Invasive Fungal Infections focused on measuring Histoplasmosis, Coccidioidomycosis, Blastomycosis

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male and female patients age > 18 years who have given written informed consent to participate

  2. Patients with a proven or probable endemic mycosis (Histoplasma, Coccidioides, Paracoccidioides, Blastomyces, Sporothrix, Talaromyces marneffei (formerly Penicillium marneffei) according to current EORTC/MSG (Mycoses Study Group) criteria, including patients who:

    • Are immunosuppressed, including as a result of HIV/AIDS
    • Have had a heart, lung or bone marrow transplant
    • Have had chemotherapy for cancer
    • Are otherwise normal hosts

Exclusion Criteria:

  1. Significant liver dysfunction as evidenced by at least 5 times greater than upper limits of normal baseline ALT (alanine aminotransferase) , AST (aspartate aminotransferase), alkaline phosphatase, or total bilirubin.
  2. Use of an alternative antifungal therapy (IV or oral) for more than 14 days for this infection, with the exception of Coccidioidomycosis. Subjects with Coccidioidomycosis who previously received fluconazole therapy for more than 14 days may be included, if in the opinion of the investigator, they are having an inadequate response or, are intolerant of fluconazole (e.g. due to adverse events). Such subjects must washout from fluconazole for 7 days (~5 half-lives of fluconazole) before starting investigational therapy.
  3. Evidence of CNS (central nervous system) infection.
  4. Unable to take PO medications.

  5. Female patients who are lactating or pregnant.

    Women should be:

    1. Postmenopausal for 1 year,
    2. Post-hysterectomy or bilateral oophorectomy,
    3. If of child bearing potential have a negative β-HCG (human chorionic gonadotropin) at screening and using highly effective method of birth control throughout course of study or remain abstinent for duration of study.
  6. Documented intolerance, allergy or hypersensitivity to an azole.
  7. Inability to comply with study treatment, study visits, and study procedures.
  8. Known history of congestive cardiac failure on medical treatment, fungal endocarditis, or other causes of ventricular dysfunction that may outweigh the benefit of itraconazole.
  9. Patients with active TB (tuberculosis)
  10. Concurrent use of astemizole, rifampin/rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine, terfenadine, ketoconazole, valproic acid, or St. John's wort in the 5 days prior to first administration of study drug.
  11. Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy.
  12. Treatment with any investigational agent in the 30 days prior to study entry.
  13. Patients unlikely to survive 30 days (including severe fungal disease defined by systolic blood pressure (SBP) < 90; hypoxia < 60).
  14. Patients with body weight < 40 kg.

Sites / Locations

  • University of Alabama at Birmingham
  • University of Arizona
  • University of California at Davis
  • Rush University
  • University of Chicago
  • Metro Infectious Disease Associates
  • University of Michigan
  • Unniversity of Minnesota
  • Washington University in St. Louis
  • Duke University Medical Center
  • University of Wisconsin
  • Hospital Santo Tomás

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SUBA itraconazole

Conventional itraconazole

Arm Description

Stage 1: Day 1-3 two 65 mg capsules three times daily with food. Days 4-42 two 65 mg capsules twice daily with food. Stage 2 : Days 43-180 two 65 mg capsules twice daily with food

Stage 1: Day 1-3 two 100 mg capsules three times daily with food. Days 4-42 two 100 mg capsules twice daily with food. Stage 2 : Days 43-180 two 100 mg capsules twice daily with food

Outcomes

Primary Outcome Measures

Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 14
Percentage of participants to achieve therapeutic itraconazole and hydroxyitraconazole levels by evaluating Inter-patient variability as calculated by co-efficient of variation on plasma specimens collected on Day 14
Frequency of Treatment Related Adverse Events Days 1-42
Comparison of the number of treatment related adverse events in each arm occurring Days 1-42.

Secondary Outcome Measures

Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 42
Percentage of patients with therapeutic itraconazole and hydroxyitraconazole levels as measured in plasma trough levels Day 42
Resolution of Signs and Symptoms of Invasive Fungal Infection on Day 42
We will measure specific signs and symptoms related to endemic fungal infection, comparing baseline findings to Day 42 findings using physical examination and patient history.
The Number of Days of Hospitalization at Day 180
The number of days of Hospitalization occurring between Day 1-180

Full Information

First Posted
February 1, 2018
Last Updated
June 21, 2023
Sponsor
University of Alabama at Birmingham
Collaborators
University of California, Davis, Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03572049
Brief Title
Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole
Acronym
MSG15
Official Title
SUBA-itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses: a Multi-center, Open-label Comparative Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
September 17, 2018 (Actual)
Primary Completion Date
May 31, 2021 (Actual)
Study Completion Date
April 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
University of California, Davis, Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a prospective, multi-center, randomized, open-label parallel arm study involving patients with proven or probable invasive endemic fungal infection to ascertain the pharmacokinetics, safety, efficacy, tolerability and health economics of oral SUBA-itraconazole compared to conventional itraconazole. Patients will receive randomized open-label study drug (SUBA-itraconazole or conventional itraconazole) over a 42 day period and then continue therapy until Day 180. Patients will be stratified based on clinically reported infection with the human immunodeficiency virus (HIV).
Detailed Description
This is a prospective, multi-center, randomized, open-label parallel arm study involving patients with proven or probable invasive endemic fungal infection to ascertain the pharmacokinetics, safety, efficacy, and tolerability of oral SUBA-itraconazole or itraconazole. Patients will receive randomized open-label study drug (either SUBA- itraconazole 130 mg twice daily or itraconazole 200 mg twice daily) over a 42-day period and then continue on their assigned open-label therapy until day 180. The study sample size will be 80 evaluable patients - target enrollment (three arms: approximately 40 histoplasmosis, 20 coccidioidomycosis, 20 other endemic fungal infections).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Fungal Infections
Keywords
Histoplasmosis, Coccidioidomycosis, Blastomycosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SUBA itraconazole
Arm Type
Experimental
Arm Description
Stage 1: Day 1-3 two 65 mg capsules three times daily with food. Days 4-42 two 65 mg capsules twice daily with food. Stage 2 : Days 43-180 two 65 mg capsules twice daily with food
Arm Title
Conventional itraconazole
Arm Type
Active Comparator
Arm Description
Stage 1: Day 1-3 two 100 mg capsules three times daily with food. Days 4-42 two 100 mg capsules twice daily with food. Stage 2 : Days 43-180 two 100 mg capsules twice daily with food
Intervention Type
Drug
Intervention Name(s)
SUBA itraconazole
Intervention Description
SUBA itraconazole study drug will consist of two 65 mg capsules to be taken three times a day with food for days 1-3 of study. For days 4-180 of study, two 65mg capsules will be taken twice daily with food.
Intervention Type
Drug
Intervention Name(s)
Conventional itraconazole
Other Intervention Name(s)
itraconazole, Sporanox
Intervention Description
Conventional itraconazole comparator drug will consist of two 100 mg capsules to be taken three times a day with food for days 1-3 of study. For days 4-180 of study, two 100 mg capsules will be taken twice daily with food.
Primary Outcome Measure Information:
Title
Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 14
Description
Percentage of participants to achieve therapeutic itraconazole and hydroxyitraconazole levels by evaluating Inter-patient variability as calculated by co-efficient of variation on plasma specimens collected on Day 14
Time Frame
Day 14
Title
Frequency of Treatment Related Adverse Events Days 1-42
Description
Comparison of the number of treatment related adverse events in each arm occurring Days 1-42.
Time Frame
Day 42
Secondary Outcome Measure Information:
Title
Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 42
Description
Percentage of patients with therapeutic itraconazole and hydroxyitraconazole levels as measured in plasma trough levels Day 42
Time Frame
Day 42
Title
Resolution of Signs and Symptoms of Invasive Fungal Infection on Day 42
Description
We will measure specific signs and symptoms related to endemic fungal infection, comparing baseline findings to Day 42 findings using physical examination and patient history.
Time Frame
Day 42
Title
The Number of Days of Hospitalization at Day 180
Description
The number of days of Hospitalization occurring between Day 1-180
Time Frame
Day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patients age > 18 years who have given written informed consent to participate Patients with a proven or probable endemic mycosis (Histoplasma, Coccidioides, Paracoccidioides, Blastomyces, Sporothrix, Talaromyces marneffei (formerly Penicillium marneffei) according to current EORTC/MSG (Mycoses Study Group) criteria, including patients who: Are immunosuppressed, including as a result of HIV/AIDS Have had a heart, lung or bone marrow transplant Have had chemotherapy for cancer Are otherwise normal hosts Exclusion Criteria: Significant liver dysfunction as evidenced by at least 5 times greater than upper limits of normal baseline ALT (alanine aminotransferase) , AST (aspartate aminotransferase), alkaline phosphatase, or total bilirubin. Use of an alternative antifungal therapy (IV or oral) for more than 14 days for this infection, with the exception of Coccidioidomycosis. Subjects with Coccidioidomycosis who previously received fluconazole therapy for more than 14 days may be included, if in the opinion of the investigator, they are having an inadequate response or, are intolerant of fluconazole (e.g. due to adverse events). Such subjects must washout from fluconazole for 7 days (~5 half-lives of fluconazole) before starting investigational therapy. Evidence of CNS (central nervous system) infection. Unable to take PO medications. Female patients who are lactating or pregnant. Women should be: Postmenopausal for 1 year, Post-hysterectomy or bilateral oophorectomy, If of child bearing potential have a negative β-HCG (human chorionic gonadotropin) at screening and using highly effective method of birth control throughout course of study or remain abstinent for duration of study. Documented intolerance, allergy or hypersensitivity to an azole. Inability to comply with study treatment, study visits, and study procedures. Known history of congestive cardiac failure on medical treatment, fungal endocarditis, or other causes of ventricular dysfunction that may outweigh the benefit of itraconazole. Patients with active TB (tuberculosis) Concurrent use of astemizole, rifampin/rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine, terfenadine, ketoconazole, valproic acid, or St. John's wort in the 5 days prior to first administration of study drug. Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy. Treatment with any investigational agent in the 30 days prior to study entry. Patients unlikely to survive 30 days (including severe fungal disease defined by systolic blood pressure (SBP) < 90; hypoxia < 60). Patients with body weight < 40 kg.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter G Pappas, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
George R Thompson, MD
Organizational Affiliation
University of California, Davis
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Andrej Spec, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of California at Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Rush University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Metro Infectious Disease Associates
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Unniversity of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710-1000
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
Hospital Santo Tomás
City
Panama
Country
Panama

12. IPD Sharing Statement

Citations:
PubMed Identifier
32457106
Citation
Thompson GR 3rd, Lewis P, Mudge S, Patterson TF, Burnett BP. Open-Label Crossover Oral Bioequivalence Pharmacokinetics Comparison for a 3-Day Loading Dose Regimen and 15-Day Steady-State Administration of SUBA-Itraconazole and Conventional Itraconazole Capsules in Healthy Adults. Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00400-20. doi: 10.1128/AAC.00400-20. Print 2020 Jul 22.
Results Reference
derived

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Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole

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