A Phase I Study to Assess Novel Ointment in a Psoriasis Plaque Test

• Change in infiltrate thickness [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
• Sonographic measurements of infiltrate thickness [ Time Frame: Day 8, Day 12 ] [ Designated as safety issue: No ]
• The AUC of the infiltrate thickness [ Time Frame: Day 8, Day 12 ] [ Designated as safety issue: No ]
• Clinical assessment scores for assessment of efficacy [ Time Frame: Day 8, Day 12 ] [ Designated as safety issue: No ]

To investigate dose-response relationship, antipsoriatic efficacy and safety of different concentrations of topical formulations of AN2728 in patients with psoriasis vulgaris

The study will be performed in 12 male subjects with stable psoriatic plaques. The study preparations and the comparators will be tested observer-blind. Treatments will be randomly assigned to the test fields. All subjects will receive all treatments, with intraindividual comparison of the treatments.

Altogether six test fields will be examined per subject (three active AN2728 ointments of different concentrations: 5 %, 2 % and 0.5 %, the active ingredient-free vehicle, a marketed corticoid preparation and a marketed topical immunomodulator). The test fields will be treated occlusively over a study period of 12 days. A topical application of approximately 200 uL of each assigned intervention will be administered per treatment, for a total of 10 treatments over a 12-day treatment period.

• Drug: AN2728 Ointment, 5%
• Drug: AN2728 Ointment, 2%
• Drug: AN2728 Ointment, 0.5%
• Drug: AN2728 Ointment Vehicle
• Drug: Betnesol®-V Creme, 0.1%
  Other Name: betamethasone 0.1%
• Drug: Protopic® Ointment, 0.1 %
  Other Name: tacrolimus 0.1 %

• Experimental: 1
  AN2728 Ointment, 5%
  Intervention: Drug: AN2728 Ointment, 5%
• Experimental: 2
  AN2728 Ointment, 2%
  Intervention: Drug: AN2728 Ointment, 2%
• Experimental: 3
  AN2728 Ointment, 0.5%
  Intervention: Drug: AN2728 Ointment, 0.5%
• Placebo Comparator: 4
  AN2728 Ointment Vehicle
  Intervention: Drug: AN2728 Ointment Vehicle
• Active Comparator: 5
  Betnesol®-V Creme (betamethasone 0.1 %)
  Intervention: Drug: Betnesol®-V Creme, 0.1%
• Active Comparator: 6
  Protopic® Ointment (tacrolimus 0.1 %)
  Intervention: Drug: Protopic® Ointment, 0.1 %

Inclusion Criteria:

• male subjects aged 18 years or older;
• subjects with psoriasis vulgaris in a chronic stable phase and stable plaques with an area sufficient for six treatment fields;
• the physical examination must be without disease findings unless the investigator considers an abnormality to be irrelevant to the outcome of the study;
• written informed consent obtained.

Exclusion Criteria:

• subjects who require systemically acting medications for the treatment of psoriasis, which might counter or influence the study objectives, e.g. corticosteroids, cytostatics;
• local treatment with antipsoriatics (except for salicylic acid in vaseline) in the 4 weeks preceding and during the study (corticosteroids 8 weeks);
• systemic treatment with antipsoriatics in the three months preceding and during the study;
• treatment with systemic or locally acting medications which might counter or influence the study aim (e.g. glucocorticosteroids, MAO inhibitors, anti-epileptic drugs, anti-psychotic drugs) or medications which are known to provoke or aggravate psoriasis, e.g. β-blocker, antimalarial drugs within two weeks before the beginning of the study and during the study;
• known allergic reactions to the active ingredients or other components of the study preparations or comparators;
• evidence of drug abuse;
• UV-therapy within four weeks before beginning and during the study;
• symptoms of a clinically significant illness that may influence the outcome of the study in the four weeks before and during the study;
• participation in another clinical trial involving pharmaceutical products in the four weeks preceding and during the study;
• in the opinion of the investigator or physician performing the initial examination the patient should not participate in the study, e.g. due to probable noncompliance or inability to understand the study and give adequately informed consent.
• subject is institutionalized because of legal or regulatory order.