Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole

NCT03572049 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MSG15MSG-15UTN U1111-1228-5154
• Study Type: interventional
• Target: 88
• Locations: 2 countries
• Sites: 12

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).

Conditions

Invasive Fungal Infections

Keywords

Histoplasmosis; Coccidioidomycosis; Blastomycosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 42

  Day 42

• Resolution of Signs and Symptoms of Invasive Fungal Infection on Day 42

  Day 42

• The Number of Days of Hospitalization at Day 180

  Day 180

Study Arms (2)

SUBA itraconazole

EXPERIMENTAL

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

Conventional itraconazole

ACTIVE COMPARATOR

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

Interventions

SUBA itraconazole 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.

SUBA itraconazole

Conventional itraconazole 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.

Also known as: itraconazole, Sporanox

Conventional itraconazole

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• University of California, Davis: collaborator
• Washington University School of Medicine: collaborator

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of California at Davis

Sacramento, California, 95817, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Metro Infectious Disease Associates

Overland Park, Kansas, 66211, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Unniversity of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710-1000, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Hospital Santo Tomás

Panama City, Panama

Location

Related Publications (2)

• 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.

  PMID: 38440302 DERIVED

• 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.

  PMID: 32457106 DERIVED

MeSH Terms

Conditions

Invasive Fungal Infections; Histoplasmosis; Coccidioidomycosis; Blastomycosis

Interventions

Itraconazole

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Dermatomycoses; Lung Diseases, Fungal; Respiratory Tract Infections; Skin Diseases, Infectious; Lung Diseases; Respiratory Tract Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Results Point of Contact

• Title: Dr. Peter G. Pappas
• Organization: University of Alabama at Birmingham

ppappas@uabmc.edu

2059347292

Study Officials

• Peter G Pappas, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• George R Thompson, MD

  University of California, Davis

  STUDY CHAIR

• Andrej Spec, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: June 28, 2018
• Study Start: September 17, 2018
• Primary Completion: May 31, 2021
• Study Completion: April 29, 2022
• Last Updated: July 7, 2023
• Results First Posted: October 6, 2022

Record last verified: 2022-09

Locations

US (11); PA (1)