Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole

NCT ID: NCT03572049

Last Updated: 2023-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-17
• Study Completion Date: 2022-04-29

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).

Conditions

Invasive Fungal Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

SUBA itraconazole

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Conventional itraconazole

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

itraconazole; Sporanox

Eligibility 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, 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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Davis

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Peter Pappas

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter G Pappas, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

George R Thompson, MD

Role: STUDY_CHAIR

University of California, Davis

Andrej Spec, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arizona

Tucson, Arizona, United States

University of California at Davis

Sacramento, California, United States

Rush University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Metro Infectious Disease Associates

Overland Park, Kansas, United States

University of Michigan

Ann Arbor, Michigan, United States

Unniversity of Minnesota

Minneapolis, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Wisconsin

Madison, Wisconsin, United States

Hospital Santo Tomás

Panama City, , Panama

Countries

United States; Panama

References

Spec A, Thompson GR, Miceli MH, Hayes J, Proia L, McKinsey D, Arauz AB, Mullane K, Young JA, McGwin G, McMullen R, Plumley T, Moore MK, McDowell LA, Jones C, Pappas PG. MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial. Open Forum Infect Dis. 2024 Jan 29;11(3):ofae010. doi: 10.1093/ofid/ofae010. eCollection 2024 Mar.

Reference Type: DERIVED

PMID: 38440302 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32457106 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MSG-15

Identifier Type: OTHER

Identifier Source: secondary_id

UTN U1111-1228-5154

Identifier Type: OTHER

Identifier Source: secondary_id

MSG15

Identifier Type: -

Identifier Source: org_study_id