MSG15: Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Completed

CT.gov ID

NCT03572049

Collaborator

University of California, Davis (Other), Washington University School of Medicine (Other)

Enrollment

Locations

Arms

43.4

Actual Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Invasive Fungal Infections	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).

Study Design

Study Type:

Interventional

Actual Enrollment :

88 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 :

Sep 17, 2018

Actual Primary Completion Date :

May 31, 2021

Actual Study Completion Date :

Apr 29, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole levels at Day 14 [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
Adherence to study medication regimens Days 1-42 [Baseline to Day 42]
The percentage of prescribed capsules returned in capsule count on Day 42
Frequency of treatment related adverse events Days 1-42 [Baseline to Day 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 [Baseline to 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 [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.
The number of days of Hospitalization at Day 180 [Baseline to day 180]
The number of days of Hospitalization occurring between Day 1-180

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of Arizona	Tucson	Arizona	United States	85724
3	University of California at Davis	Sacramento	California	United States	95817
4	Rush University	Chicago	Illinois	United States	60612
5	University of Chicago	Chicago	Illinois	United States	60637
6	Metro Infectious Disease Associates	Overland Park	Kansas	United States	66211
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	Unniversity of Minnesota	Minneapolis	Minnesota	United States	55455
9	Washington University in St. Louis	Saint Louis	Missouri	United States	63130
10	Duke University Medical Center	Durham	North Carolina	United States	27710-1000
11	University of Wisconsin	Madison	Wisconsin	United States	53705
12	Hospital Santo Tomás	Panama		Panama

Sponsors and Collaborators

University of Alabama at Birmingham
University of California, Davis
Washington University School of Medicine

Investigators

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