SUBA-Itraconazole Therapy for Coccidioidomycosis Refractory or Intolerant to Fluconazole

Brief Title

SUBA-Itraconazole Therapy for Coccidioidomycosis Refractory or Intolerant to Fluconazole

Official Title

SUBA-Itraconazole Therapy for Coccidioidomycosis Refractory or Intolerant to Fluconazole

Brief Summary

      The purpose of this study is to determine how safe, effective, and well tolerated a new
      investigational antifungal drug, SUBA-itraconazole, is for patients who have been previously
      treated with fluconazole and have had either an insufficient response to treatment with
      fluconazole or a negative reaction to fluconazole preventing their further treatment with it.
    

Detailed Description

      This is a prospective, multi-center, open-label study involving subjects with proven or
      probable coccidioidomycosis refractory to fluconazole therapy following >40 days of treatment
      or subjects with proven or probable coccidioidomycosis who are intolerant to fluconazole.

      The availability "Super Bioavailability" (SUBA) itraconazole 65 mg capsules with twice-daily
      dosing options with improved pharmacokinetics and lack of food or acidity requirements offers
      a substantial opportunity to improve the treatment of subjects with coccidioidomycosis.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

1. The Proportion of Participants Who Achieve Clinical Improvement, in All Participants Who Took at Least One Dose of Study Drug

Secondary Outcome

 Number of Participants with Treatment-Emergent Adverse Events

Condition

Coccidioidomycosis

Intervention

SUBA-itraconazole

Study Arms / Comparison Groups

 SUBA-itraconazole
Description:  Drug: SUBA-itraconazole Dosage Form: 65 mg capsules Dosage: 260 mg/day Frequency: 130 mg twice daily (BID) Duration: Up to 180 days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

28

Start Date

May 15, 2021

Completion Date

September 2022

Primary Completion Date

September 2022

Eligibility Criteria

        Inclusion Criteria:

          1. All subjects ≥ 18 years who have given written informed consent to participate

          2. Subjects with a proven or probable coccidioidomycosis according to current European
             Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG)
             criteria, including subjects 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 not immunocompromised

             Note: central nervous system (CNS) infection is an exclusionary criteria

          3. Refractory for ≥ 40 days, or intolerant to fluconazole treatment for
             coccidioidomycosis in the opinion of the investigator

               -  Refractory disease defined as failure to obtain an adequate therapeutic response
                  after ≥40 days of therapy:

               -  Lack of improvement in signs, symptoms or imaging findings OR

               -  Continued isolate of Coccidioides or histopathologic findings of • Coccidioides
                  despite antifungal therapy

               -  Rising Complement Fixation Titers

               -  Progression of disease (requires worsening of attributable signs, symptoms or
                  imaging, or a new site of infection

               -  Intolerance defined as adverse events attributable to fluconazole therapy defined
                  as organ toxicity of grade 3 or higher, nephrotoxicity (Creatinine twice the
                  upper limit of normal), or idiosyncratic reactions therapy that in the opinion of
                  the investigator may be relieved by a therapeutic change OR refusal of the
                  patient to take further fluconazole

          4. Subjects of childbearing potential should be non-pregnant and not breastfeeding (and
             not planning to become pregnant)

               -  Postmenopausal for ≥1 year

               -  Post-hysterectomy or bilateral oophorectomy

               -  If of child-bearing potential have a negative pregnancy test at screening and
                  using an acceptable effective method of birth control throughout course of study
                  or remain abstinent for duration of study. Subjects with a partner of
                  childbearing potential should agree to use appropriate contraception.

        Exclusion Criteria:

          1. Significant liver dysfunction as evidenced by total bilirubin > 1.5 × the upper limit
             of normal (ULN) range unless considered due to Gilbert syndrome, in which case > 3 ×
             the ULN, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
             levels > 1.5 x the ULN.

          2. Evidence of CNS infection.

          3. Unable to take PO medications.

          4. Documented intolerance, allergy or hypersensitivity to itraconazole.

          5. Inability to comply with study treatment, study visits, and study procedures.

          6. Known history or presence of congestive cardiac failure, fungal endocarditis, or other
             causes of ventricular dysfunction that may outweigh the benefit of itraconazole.

          7. Subjects with active tuberculosis.

          8. Concurrent use of drugs that effect SUBA™-itraconazole concentrations

             • Subjects who washout from prohibited medications can be included

          9. Any known or suspected condition of the subject that may jeopardize adherence to the
             protocol requirements or impede the accurate measurement of efficacy.

         10. Treatment with any investigational agent in the 30 days prior to study entry.

         11. Subjects unlikely to survive 30 days based on the opinion of the investigator.

         12. Subjects with body weight < 40 kg.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

George R Thompson, MD, 9167348036, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04809649

Organization ID

1666482


Responsible Party

Sponsor-Investigator

Study Sponsor

George R Thompson

Collaborators

 Mayne Pharma International Pty Ltd

Study Sponsor

George R Thompson, MD, Principal Investigator, University of California, Davis


Verification Date

April 2021