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

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ClinicalTrials.gov Identifier: NCT03572049
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
Peter Pappas, University of Alabama at Birmingham

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).

Condition or disease Intervention/treatment Phase
Fungal Infection Drug: SUBA itraconazole Drug: Conventional itraconazole Phase 2 Phase 3

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: SUBA-itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses: a Multi-center, Open-label Comparative Trial
Actual Study Start Date : September 17, 2018
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SUBA itraconazole

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

Drug: SUBA itraconazole
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.

Active Comparator: Conventional itraconazole

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

Drug: Conventional itraconazole
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.
Other Names:
  • itraconazole
  • Sporanox




Primary Outcome Measures :
  1. Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole levels at Day 14 [ Time Frame: Baseline to Day 14 ]
    Time 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

  2. Adherence to study medication regimens Days 1-42 [ Time Frame: Baseline to Day 42 ]
    The percentage of prescribed capsules returned in capsule count on Day 42

  3. Frequency of treatment related adverse events Days 1-42 [ Time Frame: Baseline to Day 42 ]
    Comparison of the number of treatment related adverse events in each arm occurring Days 1-42.


Secondary Outcome Measures :
  1. Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole levels at Day 42 [ Time Frame: Baseline to day 42 ]
    Percentage of patients with therapeutic itraconazole and hydroxyitraconazole levels as measured in plasma trough levels Day 42

  2. Resolution of signs and symptoms of invasive fungal infection on Day 42 [ Time Frame: Baseline to 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.

  3. The number of days of Hospitalization at Day 180 [ Time Frame: Baseline to day 180 ]
    The number of days of Hospitalization occurring between Day 1-180



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03572049


Contacts
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Contact: Alisa Peinhardt 205-934-9661 apeinhardt@uabmc.edu
Contact: Rachel McMullen 205-934-7292 rlmcmullen@uabmc.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Alisa Peinhardt, MAIS       apeinhardt@uabmc.edu   
Contact: Rachel McMullen, BS       rlmcmullen@uabmc.edu   
Principal Investigator: Peter G Pappas, MD         
United States, California
University of California at Davis Active, not recruiting
Sacramento, California, United States, 95817
United States, Illinois
Rush University Active, not recruiting
Chicago, Illinois, United States, 60612
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Andrea Woods    734-647-9830    woodsand@med.umich.edu   
Principal Investigator: Marisa Miceli, MD         
United States, Missouri
Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Sara Hubert, RN    314-747-1922    sarahubert@wustl.edu   
Principal Investigator: Andrej Spec, MD         
United States, Wisconsin
University of Wisconsin Active, not recruiting
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Peter G Pappas, MD University of Alabama at Birmingham
Study Chair: George R Thompson, MD University of California, Davis
Principal Investigator: Andrej Spec, MD Washington University School of Medicine

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Responsible Party: Peter Pappas, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT03572049     History of Changes
Other Study ID Numbers: MSG15
MSG-15 ( Other Identifier: Mycoses Study Group )
UTN U1111-1228-5154 ( Other Identifier: World Health Organization )
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019

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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

Additional relevant MeSH terms:
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Itraconazole
Hydroxyitraconazole
Mycoses
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors