Invasive Fungal InfectionsPhase 2/3MSG15NCT03572049
Endemic Mycoses Treatment With SUBA-itraconazole vs Itraconazole
A Phase 2/3 study testing SUBA itraconazole and Conventional itraconazole in people with Invasive Fungal Infections, run by University of Alabama at Birmingham at 12 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Invasive Fungal Infections
- What is being tested?
- SUBA itraconazole and Conventional itraconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 17 Sep 2018to 29 Apr 2022
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 18Show fewer
- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States11 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Rush University
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
Duke University Medical Center
Durham, North Carolina, 27710-1000
University of Wisconsin
Madison, Wisconsin, 53705
Unniversity of Minnesota
Minneapolis, Minnesota, 55455
Metro Infectious Disease Associates
Overland Park, Kansas, 66211
University of California at Davis
Sacramento, California, 95817
Washington University in St. Louis
St Louis, Missouri, 63130
University of Arizona
Tucson, Arizona, 85724
About this study
Official title: SUBA-itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses: a Multi-center, Open-label Comparative Trial
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).
Read the 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
- Being tested
- SUBA itraconazole, Conventional itraconazole
- Keywords
- Histoplasmosis, Coccidioidomycosis, Blastomycosis
- Medical subject headings
- Invasive Fungal Infections, Histoplasmosis, Coccidioidomycosis, Blastomycosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SUBA itraconazoleDrug
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 itraconazoleDrug
Also called itraconazole, Sporanox
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Conventional itraconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Day 42
Secondary outcomes (3)
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
Measured: Day 42
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.
Measured: Day 42
The Number of Days of Hospitalization at Day 180
The number of days of Hospitalization occurring between Day 1-180
Measured: Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2018
- Study start17 Sep 2018
- Primary completion31 May 2021
- Study completion29 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Invasive Fungal InfectionsStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Pappas, University of Alabama at Birmingham
- Investigators
- Peter G Pappas, MD, Principal investigator, University of Alabama at BirminghamGeorge R Thompson, MD, Study chair, University of California, DavisAndrej Spec, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03572049
- Sponsor's protocol ID
- MSG15
- Other IDs
- MSG-15, UTN U1111-1228-5154
- Acronym
- MSG15
- Status last verified
- Sep 2022
- First submitted
- 1 Feb 2018
- Last updated
- 7 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38440302Thompson 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.
PubMed 32457106
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SUBA-itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses: a Multi-center, Open-label Comparative Trial
- ClinicalTrials.gov ID
- NCT03572049
- Acronym / sponsor ID
- MSG15 / MSG15
- Conditions
- Invasive Fungal Infections
- Keywords
- Histoplasmosis, Coccidioidomycosis, Blastomycosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- University of California, Davis, Washington University School of Medicine
- Study start
- 17 Sep 2018 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 29 Apr 2022 (actual)
- First posted
- 28 Jun 2018 (actual)
- Results
- Posted 6 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SUBA itraconazole | Experimental | Drug: SUBA itraconazoleStage 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 | Drug: Conventional itraconazoleStage 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 |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SUBA itraconazoleSUBA 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. | Drug | SUBA itraconazole |
| Conventional itraconazoleAlso: itraconazole, SporanoxConventional 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. | Drug | Conventional itraconazole |
Primary outcome
Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 14
Time frame: 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
Frequency of Treatment Related Adverse Events Days 1-42
Time frame: Day 42
Comparison of the number of treatment related adverse events in each arm occurring Days 1-42.
3 secondary outcomes
Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 42
Time frame: Day 42
Resolution of Signs and Symptoms of Invasive Fungal Infection on Day 42
Time frame: Day 42
The Number of Days of Hospitalization at Day 180
Time frame: Day 180
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38440302Spec 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.
- Derived from this study: PubMed 32457106Thompson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter G Pappas, MD principal investigator
University of Alabama at Birmingham
George R Thompson, MD study chair
University of California, Davis
Andrej Spec, MD principal investigator
Washington University School of Medicine
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SUBA itraconazole and Conventional itraconazole in people with Invasive Fungal Infections, run by University of Alabama at Birmingham at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Panama. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of Plasma Itraconazole Levels and Hydroxyitraconazole Levels at Day 14 (time frame: Day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03572049, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2023.