Fungal Infections
Figure 2: Phase 2 Results in Vulvovaginitis 100
80 60 40 20 0 Effective treatment Alba 10 mg Alba 160 mg Alba 40 mg Alba 320 mg Complete cure Alba 80 mg Fluco 150 mg Figure 3: Phase 2 Results in Onychomycosis 100 80 60 40 20 0 Effective treatment Placebo
Alba 400 mg (24 weeks)
Alba 100 mg (36 weeks)
Alba 400 mg (36 weeks)
Clear or much improved
Alba 200 mg (36 weeks)
In a Phase 1b/2a study, capsules containing albaconazole (50, 100 and 350 mg) and placebo were administered to subjects with moccasin-type tinea pedis once weekly for four weeks. Mycological cure at week eight (intention to treat [ITT]) was 56 % (350 mg), 45 % (100 mg), 0 % (50 mg) and 8 % (placebo).44
In a Phase 2a vulvovaginal candidiasis study, single rising doses of albaconazole oral solution (10, 40, 80, 160 and 320 mg) and fluconazole (Diflucan™, 150 mg) were administered to women (10 patients/group) with acute non-complicated vulvovaginitis due to Candida spp. (see Figure 2). At final visit (24 days after treatment), cure (absence of clinical signs and symptoms) was 67 % (10 mg), 100 % (40 mg), 88 % (80 mg), 100 % (160 mg), 100 % (320 mg) and 67 % (150 mg, Diflucan™). Clinical and mycological cure was 25, 91, 88, 89, 80 and 67 %, respectively. Subjective symptom improvement of the first seven days was dose dependent, reaching 67 % at the dose of 320 mg albaconazole, compared with 33 % for fluconazole.45
In a Phase 2b study, albaconazole capsules (100, 200 and 400 mg) once weekly for 36 weeks, albaconazole 400 mg once weekly for 24 weeks or placebo were administered to patients with toenail onychomycosis (see Figure 3). Effective treatment (mycological cure plus <10 % nail affected) was obtained in 67 % (400 mg, 36 weeks), 46 % (400 mg, 24 weeks), 35 % (200 mg, 36 weeks), 23 % (100 mg, 36 weeks) and 1 % (placebo) of the patients, respectively. Complete cure (mycological cure plus 100 % cleared nails) was observed in 40, 31, 25, 14 and 0 % of the patients, respectively. Global change cleared or much improved was reported for 84, 75, 74, 54 and 11 % of the patients, respectively. Tolerability to albaconazole was excellent, with no treatment-related serious adverse events (SAEs) identified.44
Conclusion
Baseline KOH positive Culture T. rubrum
Week 48 KOH negative Culture negative
Baseline KOH negative Culture T. rubrum
Week 48 KOH negative Culture negative
Toe nails of patients affected with onychomycosis before and after once-weekly treatment with albaconazole
of 54 hours. Radioactivity was mainly excreted in faeces (60 % of the dose during 0–336 hours) with 29 % recovered in urine. The unchanged compound and two metabolites, the sulphate and glucuronide conjugates of 6-hydroxyalbaconazole, were detected in urine and faeces.42
1. Sable CA, Strohmaier KM, Chodakewitz JA, Advances in antifungal therapy, Ann Rev Med, 2008;59:361–79.
2. Aperis G, Mylonakis E, Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations, Expert Opin Investig Drugs, 2006;15:572–602.
3. Bartroli J, Turmo E, Algueró M, et al., New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)- quinazolinones, J Med Chem, 1998;41:1869–82.
4. Internal data. 90
In conclusion, albaconazole is a new oral triazole with broad-spectrum antifungal activity, unique pharmacokinetics and excellent tolerability. It has demonstrated high in vitro activities against pathogenic yeasts, dermatophytes and filamentous fungi. It has also been shown to be effective in animal models of systemic aspergillosis, candidiasis, cryptococcosis, scedosporiosis and Chagas’ disease. The compound has shown no limiting toxicity signs in preclinical studies. In Phase 1, albaconazole displayed excellent tolerability and high plasma levels with pharmacokinetics suitable for once-weekly administration. In patients, albaconazole has shown an efficacy superior to fluconazole in vulvocandidiasis after one single administration and excellent activity in toenail onychomycosis and tinea pedis when administered once-weekly. Albaconazole has the potential to become a best-in-class drug for the oral treatment of a variety of fungal infections. n
5. Ramos G, Cuenca-Estrella M, Monzón A, et al., In vitro comparative activity of UR-9825, fluconazole (FLZ) and itraconazole (ITR) against clinical isolates of Candida spp, J Antimicrob Chemother, 1999;44:283–6.
6. Garau M, Pereiro M Jr, del Palacio A, In vitro susceptibilities of Malassezia species to a new triazole, Albaconazole (UR-9825), and other antifungal compounds, Antimic Agents Chemother, 2003;47:2342–4.
7. Alves SH, Da Matta DA, Azevedo AC, et al., In vitro activities
of new and conventional antimycotics against fluconazole-susceptible and non-susceptible brazilian Candida spp isolates, Mycoses, 49:220–5.
8. Arechavala AI, Bianchi MH, Robles AM, et al., Identificación y sensibilidad frente a fluconazol y albaconazol de 100 cepas de levaduras aisladas de flujo vaginal, Rev Iberoam Micol, 2007;24:305–8.
9. Miller JL, Schell WA, Wills EA, et al., In vitro and in vivo efficacies of the new triazole Albaconazole against
Albaconazole was concluded to have a good cardiac safety profile after analysis of 2,872 ECGs collected from four Phase 1 trials involving 126 volunteers administered with albaconazole (n=103) or placebo (n=23).43
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