The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not

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1 The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No: W /STF Title : A Phase 1, Evaluator-Blinded, Randomized, Vehicle-Controlled Study to Evaluate the Contact Sensitization Potential of Topically-Applied Tazarotene Foam in Healthy Volunteers Rationale: Tazarotene is a retinoid prodrug that has been approved by the Food and Drug Administration (FDA) in cream and gel formulations (Tazorac 0.1%; Allergan, Inc.) for the treatment of acne vulgaris. In clinical dermal safety studies, tazarotene cream and gel were associated with irritation, but did not induce allergic contact sensitization, phototoxicity, or photoallergy. Stiefel is developing tazarotene 0.1% formulated in an emulsion-based foam vehicle for topical application in the treatment of acne vulgaris. This study will assess the potential of tazarotene foam to induce contact sensitization following repeated exposure on the skin of healthy volunteers. The study design is based on the United States FDA Guidance for Industry, Skin Irritation and Sensitization Testing of Generic Transdermal Drug Products. Phase: 1 Study Period: 31 March 2010 (first subject, first visit) / 26 June 2010 (last subject, last visit) Study Design: Single-center, evaluator-blinded, randomized, vehicle-controlled, sensitization study in healthy adult volunteers. Subjects were exposed to patches containing tazarotene foam and patches containing vehicle foam for 3 weeks (Induction Phase). Following a ~2-week Rest Period, subjects were exposed to tazarotene foam and vehicle foam patches on naïve sites for 48 hours (Challenge Phase) and skin responses were evaluated. Centres: 1 center in the United States Indication: Not applicable healthy volunteer study Treatment: Tazarotene foam 0.1% administered topically either on a patch (200 μl) or as open application (50 μl). Semi- occlusive patches were used. However, at the investigator s discretion, study product could be applied using semi-open patches or open-application conditions during the Challenge Phase and Re-challenge Phase if a strong erythema reaction was observed during the Induction Phase. Objectives: The objective of this study was to evaluate the contact sensitization potential of tazarotene foam 0.1%. Statistical Methods: Descriptive statistics were used to provide results. No formal statistical testing was performed. Frequency counts and percentages of subjects with inflammatory skin responses were tabulated by visit and study product. The potential for contact sensitization was determined by the investigator s evaluation of skin reaction grades and clinical observations during the Challenge Phase. Adverse events, concomitant medications, and reasons for withdrawal from the study were summarized using frequencies and percentages. The Medical Dictionary for Regulatory Activities (Version 11.0) was used for coding of AEs and the World Health Organization Drug Dictionary (WHO2009Q1) was used for coding of concomitant medications. Adverse event onset, severity, relationship to study product, action taken, and resolution were presented by subject. Study Population: Healthy male and female volunteers 18 to 65 years of age with Fitzpatrick skin types I (always burns easily; never tans), II (always burns easily; tans minimally), III (burns moderately; tans gradually), or IV (rarely burns; tans with ease). Subjects must also have agreed to use a medically-acceptable method of contraception throughout the duration of the study. Additional criteria for women of childbearing potential (defined as being biologically capable of becoming pregnant), including perimenopausal women who were fewer than 2 years from their last menses, were (1) a regular menstrual cycle before study entry (as reported by the subject) and (2) a negative urine pregnancy test within 2 weeks of the first application of study product. Females who were pregnant, trying to become pregnant, or breastfeeding were not included. Number of Subjects: Safety Analysis Set Per-Protocol Analysis Set Planned N 240 Not available Dosed N 254 Not available Completed n (%) 215 (84.6) Not available Total Number Subjects Withdrawn N (%) 39 (15.4) Not available Withdrawn due to Adverse Events n (%) 3 (1.2) Not available Withdrawn due to Lack of Efficacy n (%) 0 Not available Withdrawn for Other Reasons n (%) 36 (14.2) Not available Demographics: Safety Analysis Set Per-Protocol Analysis Set 1

2 N (ITT) Females: Males 152: :78 Mean Age in Years (sd) 46 (12.5) 47.3 (12.0) Mean Weight in Kg (sd) Not available Not available White n (%) 242 (95.30) 197 (94.70) Fitzpatrick skin type, n (%) I 4 (1.60) 4 (1.90) II 63 (24.80) 54 (26.00) III 116 (45.70) 101 (48.60) IV 71 (28.00) 49 (23.60) 2

3 Evaluation of Skin Reactions: Challenge Phase Number and Percentage of Subjects with Each Erythema Grade at Challenge (Per-Protocol Analysis Set) Patch Site Assessment at Challenge 30 Min. 24 Hr. 48 Hr. 72 Hr. Erythema Grade n (%) n (%) n (%) n (%) Tazarotene foam (N = 200 a ) 0 = no visible reaction 136 (68.00) 129 (64.50) 145 (72.50) 171 (85.50) + = slight, confluent, or patchy 29 (14.50) 34 (17.00) 25 (12.50) 11 (5.50) 1 = mild (pink) 26 (13.00) 26 (13.00) 25 (12.50) 16 (8.00) 2 = moderate (definite redness) 9 (4.50) 11 (5.50) 4 (2.00) 2 (1.00) 3 = strong (very intense redness) (0.50) 0 Vehicle foam (N = 208) 0 = no visible reaction 169 (81.25) 181 (87.02) 191 (91.83) 199 (95.67) + = slight, confluent, or patchy 28 (13.46) 15 (7.21) 10 (4.81) 7 (3.37) 1 = mild (pink) 8 (3.85) 11 (5.29) 5 (2.40) 2 (0.96) 2 = moderate (definite redness) 3 (1.44) 1 (0.48) 2 (0.96) 0 3 = strong (very intense redness) a. Eight subjects (Nos. 2030, 2044, 2051, 2074, 2094, 2110, 2123, and 2217) did not have the tazarotene foam patch applied during Challenge due to strong irritation scores that were observed after the first or second Induction application. Number and Percentage of Subjects with Local Skin Reactions and Superficial Effects at Challenge (Per-Protocol Analysis Set) Patch Site Assessment at Challenge 30 Min. 24 Hr. 48 Hr. 72 Hr. n (%) n (%) n (%) n (%) Tazarotene foam (N = 200 a ) Local Skin Reaction: No local skin reactions 198 (99.00) 198 (99.00) 196 (98.00) 198 (99.00) P = papule 2 (1.00) 2 (1.00) 4 (2.00) 2 (1.00) Superficial Effects: No superficial effects 198 (99.00) 199 (99.50) 196 (98.00) 196 (98.00) c = scab (0.50) 1 (0.50) g = glazing 2 (1.00) gy = glazing, peeling 0 1 (0.50) 2 (1.00) 2 (1.00) gyf = glazing, peeling, fissuring (0.50) y = peeling (0.50) 0 Vehicle foam (N = 208) Local Skin Reaction: No local skin reactions 207 (99.52) 207 (99.52) 207 (99.52) 206 (99.04) P = papule 1 (0.48) 1 (0.48) 1 (0.48) 2 (0.96) Superficial Effects: No superficial effects 208 (100) 208 (100) 208 (100) 208 (100) a. Eight subjects (Nos. 2030, 2044, 2051, 2074, 2094, 2110, 2123, and 2217) did not have the tazarotene foam patch applied during Challenge due to strong irritation scores that were observed after the first or second Induction application. 3

4 Evaluation of Skin Reactions: Repeat Challenge Phase Number and Percentage of Subjects with Each Erythema Grade at Rechallenge Patch Site Assessment at Repeat Challenge 30 Min. 24 Hr. 48 Hr. 72 Hr. Erythema Grade n (%) n (%) n (%) n (%) Tazarotene foam (N = 2 a ) 0 = no visible reaction 0 1 (50.00) 1 (50.00) 1 (50.00) + = slight, confluent, or patchy = mild (pink) 1 (50.00) = moderate (definite redness) 1 (50.00) 0 1 (50.00) 1 (50.00) 3 = strong (very intense redness) 0 1 (50.00) 0 0 Vehicle foam (N = 3) 0 = no visible reaction 1 (33.33) 2 (66.67) 2 (66.67) 2 (66.67) + = slight, confluent, or patchy = mild (pink) 2 (66.67) 0 1 (33.33) 1 (33.33) 2 = moderate (definite redness) 0 1 (33.33) = strong (very intense redness) a. Subject 2110 was not exposed to tazarotene foam at Rechallenge due to strong irritation scores that were observed during Induction. Individual Assessment Scores for Subjects who were Rechallenged Induction Challenge Rechallenge Day Day Day Day Day Day Day Day Day Subject Product Min Hr Hr Hr Min Hr Hr Hr 2033 Tazarotene 0 + 2gy 2gy 2gy 2gy 2gy 2gy 2gy 2 2 1P 1gy Vehicle gy 1g 1g +g a Tazarotene 1 3 2g 1gyc 0c c Vehicle g 0 2 2P Tazarotene Original gy 2gc 1c gy 3gy 2gyf y 1 st Move Vehicle y P Abbreviations: min = minute; hr = hour; c = scab; f = fissuring; g = glazing; P = papule; y = peeling a. Subject 2110 was not exposed to tazarotene foam at Challenge or Rechallenge due to strong irritation scores that were observed during Induction. Note: Induction scores are for the original patch site, unless otherwise specified. Challenge and Rechallenge scores are for naïve sites. Safety results: An adverse event (AE) was defined as an AE encountered or spontaneously reported by the subject and/or elicited by investigators or designees after the consent document was signed or at any time throughout the study (prior to and after receiving study product). A serious adverse event (SAE) was defined as an SAE that happened at any time, including times prior to taking study products or occurred during the course of the study or its follow-up period (ie, following subject consent). 4

5 Twenty-three (9.1%) of the 254 subjects in the Safety analysis set reported a total of 32 AEs. No AE (preferred term) was reported by more than 1 subject except for upper respiratory tract infection (2 subjects, 0.8%). No system organ class had AEs reported by more than 5 subjects (infections and infestations; injury, poisoning and procedural complications; 5 subjects [2.0%] each). No pregnancies were reported during this study. Adverse Events: Safety Analysis Set Per-Protocol Analysis Set N (ITT) 254 Not available No. subjects with AEs n (%) 23 (9.1) Not available Most Frequent AEs Not available Anaemia 1 (0.4) Not available Tachycardia 1 (0.4) Not available Hypothyroidism 1 (0.4) Not available Food poisoning 1 (0.4) Not available Gastric ulcer 1 (0.4) Not available Nausea 1 (0.4) Not available Reflux oesophagitis 1 (0.4) Not available Application site irritation 1 (0.4) Not available Application site pruritus 1 (0.4) Not available Application site rash 1 (0.4) Not available Seasonal allergy 1 (0.4) Not available Upper respiratory tract infection 2 (0.8) Not available Gastroenteritis 1 (0.4) Not available Oral herpes 1 (0.4) Not available Staphylococcal infection 1 (0.4) Not available Tooth abscess 1 (0.4) Not available Contusion 1 (0.4) Not available Injury 1 (0.4) Not available Joint sprain 1 (0.4) Not available Post procedural haemorrhage 1 (0.4) Not available Skin laceration 1 (0.4) Not available Diabetes mellitus 1 (0.4) Not available Dizziness 1 (0.4) Not available Syncope 1 (0.4) Not available Anxiety 1 (0.4) Not available Depression 1 (0.4) Not available Nephrolithiasis 1 (0.4) Not available Atelectasis 1 (0.4) Not available Acne 1 (0.4) Not available Rash 1 (0.4) Not available Rash pruritic 1 (0.4) Not available 5

6 Serious Adverse Events, n (%) [n considered by the investigator to be related, possibly related, or probably related to study medication]: There was 1 death during the study. Subject 2090 died on study Day 20; the cause of death was blunt force trauma (preferred term injury ) resulting from a traffic accident. Including the death described, there were 3 SAEs in 3 subjects (1%) [0 (0%)] during this study. Serious Adverse Events (Safety Analysis Set) Subject Study Day Action Number Verbatim Term/ Preferred Term Start/End Severity Related Taken 2090 Blunt force trauma/ Injury 20 / 20 Severe No Drug withdrawn 2104 Contusion to feet and ankles/ Contusion 14 / 20 Moderate No Drug withdrawn 2151 Secondary post-tonsillectomy hemorrhage/ Postprocedural haemorrhage 2 / 10 Severe No Drug withdrawn 6