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| ID | Type | Description | Link |
|---|---|---|---|
| MSG-15 | Other Identifier | Mycoses Study Group | |
| UTN U1111-1228-5154 | Other Identifier | World Health Organization |
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| Name | Class |
|---|---|
| University of California, Davis | OTHER |
| Washington University School of Medicine | OTHER |
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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).
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Resolution of Signs and Symptoms of Invasive Fungal Infection on Day 42 |
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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:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| University of Arizona |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38440302 | Derived | 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. | |
| 32457106 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 19, 2020 |
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| 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. |
|
|
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 |
| The Number of Days of Hospitalization at Day 180 | The number of days of Hospitalization occurring between Day 1-180 | Day 180 |
| Tucson |
| Arizona |
| 85724 |
| United States |
| University of California at Davis | Sacramento | California | 95817 | United States |
| Rush University | Chicago | Illinois | 60612 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Metro Infectious Disease Associates | Overland Park | Kansas | 66211 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Unniversity of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Washington University in St. Louis | St Louis | Missouri | 63130 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710-1000 | United States |
| University of Wisconsin | Madison | Wisconsin | 53705 | United States |
| Hospital Santo Tomás | Panama City | Panama |
| 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. |
| FG001 | 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 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 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. |
| BG001 | 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 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Number | percentage of participants | 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. | Posted | Number | adverse events | 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 | Posted | Number | percentage of participants | 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. | Posted | Count of Participants | Participants | Day 42 |
|
| |||||||||||||||||||||||||||||||
| Secondary | The Number of Days of Hospitalization at Day 180 | The number of days of Hospitalization occurring between Day 1-180 | Posted | Mean | Full Range | Days | Day 180 |
|
|
Data regarding all adverse events were collected over 180 days (approximately 6 months).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 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. | 1 | 42 | 4 | 42 | 16 | 42 |
| EG001 | 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 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. | 0 | 46 | 12 | 46 | 22 | 46 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| UTI Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Death | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypomolar Nonketotic Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Edema, lower extremities | Vascular disorders | Systematic Assessment |
| ||
| Hypertrophic Obstructive Cardiomyopathy | Cardiac disorders | Systematic Assessment |
| ||
| Unintended Pregnancy | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Pain in foot | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Dypnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Liver Toxicity | Hepatobiliary disorders | Systematic Assessment |
| ||
| Ascites, worsening | Hepatobiliary disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Motor Vehicle Accident | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Gastro-intestinal hemorrhage with hematemesis | Gastrointestinal disorders | Systematic Assessment |
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| Emesis | Gastrointestinal disorders | Systematic Assessment |
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| Nausea, worsening | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal Cramping | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea, worsening | Gastrointestinal disorders | Systematic Assessment |
| ||
| GI Bleed | Gastrointestinal disorders | Systematic Assessment |
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| Cardiac Catheterization | Cardiac disorders | Systematic Assessment |
| ||
| Bradycardia | Cardiac disorders | Systematic Assessment |
| ||
| Chest Pain | Cardiac disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Weight Gain | General disorders | Systematic Assessment |
| ||
| Weakness | General disorders | Systematic Assessment |
| ||
| Rash | General disorders | Systematic Assessment |
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| Pruritus | General disorders | Systematic Assessment |
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| Night sweats | General disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Lightheadedness | General disorders | Systematic Assessment |
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| Joint Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Insomnia | Nervous system disorders | Systematic Assessment |
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| Hypertension | Cardiac disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
| ||
| Emesis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Edema | Cardiac disorders | Systematic Assessment |
| ||
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Blurry Vision | General disorders | Systematic Assessment |
| ||
| Anorexia | General disorders | Systematic Assessment |
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| Weight loss | General disorders | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Dyspnea | Reproductive system and breast disorders | Systematic Assessment |
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| Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Chest Pain | Cardiac disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Peter G. Pappas | University of Alabama at Birmingham | 2059347292 | ppappas@uabmc.edu |
| Jul 12, 2022 |
| Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D000072742 | Invasive Fungal Infections |
| D006660 | Histoplasmosis |
| D003047 | Coccidioidomycosis |
| D001759 | Blastomycosis |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D003881 | Dermatomycoses |
| D008172 | Lung Diseases, Fungal |
| D012141 | Respiratory Tract Infections |
| D012874 | Skin Diseases, Infectious |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
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| Unknown or Not Reported |
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| Participants |
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| Participants |
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