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Clinical Trial Results

P-113 for Oral Candidiasis

A Phase IIb dose-ranging clinical trial demonstrated positive results. The Phase IIb study involved over 200 seropositive HIV patients, demonstrated that P-113 efficacy profile compares favorably to the efficacy of Nystatin, a current standard of care for topical treatment of oral Candidiasis.

Opportunistic growth of Candida occurs in people with defective immune systems, or as a result of salivary dysfunction, and can be life-threatening if not treated. Candida albicans is the most common fungal pathogen among immune-compromised, hospitalized patients, accounting for roughly 50-60% of all bloodstream fungal isolates. Localized Candida infections, if untreated, can spread from the primary site of infection through the blood stream to cause a disseminated infection. Disseminated fungal infections are associated with a high mortality rate.

Current treatments for Candida infections are either only marginally efficacious, have poor patient compliance characteristics, can cause serious side effects, can lead to drug-resistance and/or have multiple drug interaction issues.

  • Nystatin: Topical - Modest Efficacy - Poor Palatability
  • Azoles: Systemic/Topical Potential for resistance Drug Interactions
  • Ampotericin B: Systemic, Severe Side Effects

P-113 is a 12 amino-acid antimicrobial peptide derived from a naturally occurring histatin protein found in saliva. In vitro studies demonstrate that it has potent anti-fungal activity against the Candida albicans, including drug-resistant HIV patient isolates.

Modes of Action

P-113 is an amphipathic molecule that interacts with fungal cell membranes, altering permeability which causes cytoplasmic leakage and cell death. P-113 also interacts with fungal mitochondria causing production of reactive oxygen species and fungal cell destruction. This activity is unique to histatin proteins. In addition, P-113 is active against growing cells, stationary phase cells and fungal biofilms. Rapid fungal lysis of fungal cells in a wide range of growth states may affect a more rapid and complete clinical cure.

The P-113 formulation is a sugar-free, pleasant tasting, non-viscous aqueous solution with a neutral pH. The prolonged half-life of PAC-113 in the saliva has the potential to extend the duration of the therapeutic effect.

Phase IIb Study - Positive Results

Results from Phase IIb clinical trial evaluating the safety and efficacy of P-113. demonstrate that PAC-113 is generally safe, well tolerated, and is effective in the treatment of oral Candida infection.

Study Design

PAC-113 mouthrinse vs. Nystatin oral suspension.
Randomized, examiner-blinded, parallel design clinical trial.
14-day treatment phase with a 14-day follow-up period.

Treatment Arms

Eligible subjects will be randomized to one of the following treatment arms:
0.15% PAC-113 mouthrinse (5 mL, 4-times per day).
0.075% PAC-113 mouthrinse (5 mL, 4-times per day).
0.0375% PAC-113 mouthrinse (5 mL, 4-times per day).
Nystatin oral suspension (5 mL, 4-times per day).

Positive Results

The optimal dose of P-113 demonstrated a 34% increase in primary endpoint efficacy level (complete clinical cure rate at Day 19) for the Per Protocol analysis as compared to Nystatin, and a 50% increase in the corresponding Intent to Treat analysis.

Safety data was also generated from Phase I/II and Phase IIb trials, as well as Phase I and Phase II trials conducted in the US by Periodontix Inc. (subsequently acquired by Demegen, Inc.) prior to PAC-113 being in-licensed by Pacgen in 2005. The studies conducted by Periodontix/Demegen were in oral rinse and gel formulation for prevention of bacterial periodontal disease.