A Trial Involving Treatment of BB2603 in Subjects With Distal Subungual Onychomycosis of the Toenail
Condition: Distal Subungual Onychomycosis; Fungal Infection; Fungus, Nail
MeSH terms: Mycoses; Onychomycosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will be a multicenter, international, randomized, vehicle-controlled,
      parallel-group, double-blinded study. Subjects who are eligible to participate with a
      confirmed diagnosis of Distal Subungual onychomycosis (DSO) of the toenail will be randomized
      and participate in one of the following treatment groups: BB2603-1: 0.01% terbinafine/0.03%
      polyhexanide formulation, or BB2603-3: 0.03% terbinafine/0.09% polyhexanide formulation, or
      BB2603-10: 0.1% terbinafine/0.3% polyhexanide formulation, or Vehicle: 0.3% polyhexanide/20%
      ethanol/water formulation. The subject in each treatment group will be treated twice daily
      (BID) for 12 weeks and then complete a 28-day post-treatment visit.
    

Detailed description: 
      Onychomycosis (OM; fungal nail infection) is a common and contagious fungal infection of the
      nail plate or nail bed, leading to the gradual destruction of the nail plate. OM is
      considered the most prevalent of the nail ailments, accounting for about 50% of all diseased
      nails and about 30% of cutaneous fungal infections. The prevalence of OM is reported to be
      23% across Europe, 13.8% in North America and approximately 10% in Japan, with the prevalence
      increasing in Western countries, presumably due to lifestyle changes and the ageing of the
      population.

      Distal subungual onychomycosis (DSO) is the most common form of OM, characterised by invasion
      of the nail bed and underside of the nail plate beginning at the hyponychium. This infection
      is visualised as nails with normal surface texture and thickness but variable "bays" of white
      nail that extend from the distal nail tip proximally into the area of the nail bed. The vast
      majority of cases of OM are caused by dermatophyte fungi. In 80% to 98% of affected
      individuals, Trichophyton rubrum with additional infections caused by Trichophyton
      mentagrophytes var interdigitale (commonly referred to as Trichophyton mentagrophytes) or
      Epidermophyton floccosum. The dermatophyte Trichophyton rubrum is the major cause of tinea
      pedis (TP; athlete's foot) and OM. OM is a progressive disease; if left untreated, OM can
      lead to permanent nail damage and associated discomfort.

      Onychomycosis is currently treated with surgery, medical devices (eg laser therapy), oral or
      topical anti-fungal agents or a combination of both. Oral terbinafine, when used for a
      minimum of 3 months, can achieve an efficacy of 38% or higher if treatment is extended but
      has a significant drug-interaction and side effect profile, including liver failure, and
      periodic monitoring (after 4-6 weeks of treatment) of liver function test is recommended.
      Topical agents are used for up to 18 months but have significantly lower efficacy rates of
      less than 20%.

      Terbinafine is a well-established synthetic allylamine anti-fungal developed by Sandoz (now
      Novartis) and commercially available worldwide for more than 25 years in different oral and
      topical formulations as a dermal cream (1%), emulsion gel (1%), solution/spray (1%), as well
      as oral tablets (250 mg and 125 mg). It is highly hydrophobic in nature and tends to
      accumulate in skin, nails, and fatty tissues. Terbinafine's anti-fungal mechanism of action
      is by inhibition of squalene epoxidase in the fungal cell membrane. This leads to a
      deficiency in ergosterol and an intracellular accumulation of squalene, resulting in fungal
      cell rupture/lysis (fungicidal activity).

      Dermatophytoses of nails, in contrast to those at other body sites, are particularly
      difficult to eradicate with drug treatment. This is the consequence of factors intrinsic to
      the nail (the hard, protective nail plate, sequestration of pathogens between the nail bed
      and plate, and slow growth of the nail). The unique barrier properties of the nail plate,
      which hampers the passage of anti-fungal drugs in a concentration required to eradicate the
      deeply-seated causative fungi in the nail bed, is a specific challenge.

      As such, there is a recognized need for a simple, effective and curative topical treatment
      for OM. Furthermore, topical treatment may result in minimal adverse systemic events and
      possibly improved adherence.
    

Intervention name(s): BB2603-1; BB2603-3; BB2603-10; Vehicle
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): Treatment with topical spray twice-daily (BID) BB2603-1: 0.01% terbinafine; Treatment with topical spray twice-daily (BID) BB2603-3: 0.03% terbinafine; Treatment with topical spray twice-daily (BID) BB2603-10: 0.1% terbinafine; Treatment with topical spray twice-daily (BID): 0.3% polyhexanide/ 20% ethanol/ water formulation.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-Blinded
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: DSO; Fungual Infection; Fungus, Nail