This is an open-label, dose-titration trial to study the efficacy, safety, and pharmacokinetics of oral cochleate amphotericin B (CAMB) in the treatment of mucocutaneous candidiasis infections in patients who are refractory or intolerant to standard non intravenous therapies.

Patients aged 18 to 75 years with mucocutaneous candidiasis (esophageal, oropharyngeal, or vulvovaginal) who are refractory or intolerant to standard non-intravenous therapies will be enrolled. Patients will initially be treated in a short-term dose titration period, where the dose may be increased in patients that do not respond clinically. Patients who do not respond clinically to the highest dose of drug will discontinue the protocol. Patients that respond to treatment and tolerate the study medication will be eligible to enter a long-term extension (up to 60-months).

Inclusion Criteria:

• Patients must have a clinical diagnosis of at least one of the following:

• Persistent oropharyngeal candidiasis (OPC) for greater than or equal to 5 days documented on at least one occasion by potassium hydroxide (KOH) test or fungal stain and confirmed by mycological culture to be azole resistant within the previous 6 months and/or intolerance to standard non intravenous therapies or lack of improvement or worsening of OPC after receipt of appropriately dosed oral azole therapy.

• Esophageal candidiasis (EC) associated with clinical symptoms of retrosternal pain, odynophagia, and/or pain with swallowing and documented by esophageal biopsy or visualization with culture documenting azole resistance within the previous 6 months and/or intolerance to standard non-intravenous therapies or lack of improvement or worsening of EC after appropriately dosed azole therapy.

• Persistent vulvovaginal candidiasis (VVC) for greater than or equal to 5 days as documented by presence of vaginal symptoms and a positive wet mount showing Candida structures and confirmed by a vaginal culture positive for Candida with azole resistance within the previous 6 months and/or intolerance to standard non intravenous therapies or lack of improvement or worsening of VVC after appropriately dosed azole therapy.

• Patient is expected to survive for greater than or equal to 6 months.

• Willing to have samples stored for future research.

• Agree to use highly effective contraception.

  • Contraception: Because the effects of CAMB on the developing human fetus are unknown, sexually active patients of childbearing potential must agree to use highly effective contraception as outlined below before study entry and for the duration of study participation. Females of childbearing potential must have a negative pregnancy test result before receiving CAMB. During the course of the study, if a patient becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are:

    • Intrauterine device (IUD) or equivalent.
    • Hormonal contraceptives (eg, consistent, timely and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the patient uses contraceptive pill, patch, or ring, then a barrier method (eg, male/female condom, cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.
    • Be in a stable, long-term monogamous relationship, per principal investigator (PI) assessment, with a partner that does not pose any potential pregnancy risk, eg, has undergone a vasectomy at least 6 months prior to first dose of study agent or is of the same sex as the patient.
    • Have had a hysterectomy and/or a bilateral tubal ligation or both ovaries removed.

Exclusion Criteria:

• Allergy to any amphotericin B (AMB) product or any component of CAMB (eg, phosphatidylserine)

• Have evidence of systemic fungal infections requiring intravenous antifungal therapy

• Pregnant or nursing women, and women intending to become pregnant during the study period

• Had a concomitant medical condition that could interfere with study drug evaluation or that is a contraindication to the proposed investigational treatment based upon known agent safety profile or toxicities.

• Had any of the following laboratory abnormalities at the screening visit:

  • Alanine Transaminase (ALT), Aspartate Transaminase (AST) and Alkaline phosphatase (ALP) > 2.5 times the upper limit of normal (ULN).
  • Total bilirubin level > 2.5 times the ULN
  • Serum creatinine level > 2 times the ULN
  • Absolute neutrophil count less than 500 cells/microliter
  • Potassium level less than 3.5 mmol/L

• Exposure to any investigational agent within 4 weeks prior to Day 0 (Baseline).

• Current or recent history (past 12 months) of drug or alcohol abuse.

• Use of intravenous AMB products within 1-week of start of study drug administration

• Use of non-intravenous AMB products (such as oral AMB swishes) within 72 hours prior to start of study drug administration

• Any other condition the investigator believes would interfere with the patient s ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.

Adverse events were collected over the entire study period up to 60 months

Adverse events were noted at each study visit

Did not reach target number of participants (small sample size). All participants were female and Caucasian.