Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole

Invasive Fungal Infections Clinical Trial

— MSG15  

Official title:

SUBA-itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses: a Multi-center, Open-label Comparative Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03572049
• Other study ID #: MSG15
• Secondary ID: MSG-15UTN U1111-
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 17, 2018
• Est. completion date: April 29, 2022

Study information

• Verified date: September 2022
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: April 29, 2022
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Invasive Fungal Infections
• Mycoses

Intervention

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.
• 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.

Locations

Country	Name	City	State
Panama	Hospital Santo Tomás	Panama
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Rush University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Wisconsin	Madison	Wisconsin
United States	Unniversity of Minnesota	Minneapolis	Minnesota
United States	Metro Infectious Disease Associates	Overland Park	Kansas
United States	University of California at Davis	Sacramento	California
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Arizona	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	University of California, Davis, Washington University School of Medicine

Countries where clinical trial is conducted

United States,  Panama, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 14
Primary	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.	Day 42
Secondary	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	Day 42
Secondary	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.	Day 42
Secondary	The Number of Days of Hospitalization at Day 180	The number of days of Hospitalization occurring between Day 1-180	Day 180