A Study to Evaluate the Safety and Efficacy of Tazarotene Foam, 0.1%, in Subjects With Common Facial Acne

Study Overview
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Brief Summary
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The purpose of this study is to assess safety and efficacy of a new foam formulation of tazarotene in subjects with acne vulgaris.

Detailed Description
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A multicenter, randomized, double-blind, vehicle-controlled, parallel-group study comparing tazarotene foam with vehicle foam in subjects with acne vulgaris. Approximately 742 subjects will be enrolled and randomized to 1 of the 2 study product groups in a 1:1 ratio (tazarotene foam: vehicle foam). Subjects will apply tazarotene foam or vehicle foam to the entire face once daily for 12 weeks; study visits will occur at baseline (week 0/day 1) and at weeks 2, 4, 8, and 12.

Official Title
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A Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Tazarotene Foam, 0.1%, in Subjects With Acne Vulgaris

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Tazarotene Foam
* Drug: Vehicle Foam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 12 through 45 years, inclusive, who is in good general health. An ISGA score of 3 or greater at baseline. Lesion counts meeting both of the following criteria: Between 25 and 50 facial inflammatory lesions and no more than 1 facial nodular lesion (<5mm), with NO cystic lesions. Between 30 and 125 facial noninflammatory lesions, excluding nasal lesions. - Regular menstrual cycle prior to study entry for females of childbearing potential. Negative urine pregnancy test for females of childbearing potential. • Sexually active females of childbearing potential participating in the study must agree to use a medically acceptable method of contraception while receiving protocol-assigned product. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant; including perimenopausal women who are less than 2 years from their last menses. Women who are not currently sexually active must agree to use medically accepted method of contraception should they become sexually active while participating in the study. Male subjects and/or their partners must use a medically acceptable form of contraception. Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed. Ability and willingness to follow all study procedures, attend all scheduled visits, and successfully complete the study. Exclusion Criteria: Female who is pregnant, trying to become pregnant, or breast feeding. Use of topical antibiotics on the face within the past 2 weeks. Use of systemic antibiotics for acne treatment within the past 4 weeks. Concurrent use of medications known to be photosensitizers (eg, thiazides, tetracyclines) because of the possibility of augmented photosensitivity. Use of topical corticosteroids on the face within the past 2 weeks or systemic corticosteroids within the past 4 weeks. Use of systemic retinoids (eg, isotretinoin) within the past 6 months. Treatment with estrogens, androgens, or anti-androgenic agents for 12 weeks or less immediately prior to study enrollment. Subjects that have been treated with these medications for more than 12 consecutive weeks prior to study enrollment are allowed to enroll as long as they do not expect to change the dose or drug, or to discontinue use during the study and it has not been indicated for the treatment of acne vulgaris. Use of topical anti-acne medications (eg, benzoyl peroxide, retinoids, or salicylates) within the past 2 weeks. Concomitant use of facial products such as: abradants, facials, peels containing glycolic or other acids, masks, washes or soaps. Concomitant use of medications that are reported to exacerbate acne (eg, mega-doses of certain vitamins, haloperidol, and immunosuppressants such as cyclosporine) as these may impact efficacy assessments. Multivitamins, iron supplements, and folate are acceptable. Facial procedure (eg, blue light, chemical or laser peel, or microdermabrasion) within the past 4 weeks. Require or desire excessive or prolonged exposure to ultraviolet light during the study. Known hypersensitivity or previous allergic reaction to any of the active components of the study product. A significant medical history of or currently immunocompromised. Use of any investigational product within the past 4 weeks or currently participating in another clinical study. Any other condition which, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study. Any major illness within 30 days before study enrollment. Currently lives in the same household as currently enrolled subjects; is an employee of Stiefel, an investigator, or a CRO involved in the study; or is an immediate family member (eg, partner, offspring, parents) of an employee involved in the study

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Tazarotene foam, 0.1% | Drug: Tazarotene Foam<br>* Tazarotene foam once a day application to the face<br>|
| Placebo Comparator: 2<br>Vehicle Foam | Drug: Vehicle Foam<br>* Vehicle Foam once a day application to the face<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Lesion Counts (LCs) From Baseline to Week 12 | LC: count of all inflammatory lesions (ILs, i.e., papules, pustules, and nodules) and non-inflammatory lesions (NILs, i.e., open and closed comedones) at Baseline and at Week 12. Total lesions (TLs) were calculated as the sum of ILs and NILs. LC was confined to the face (including forehead, nose, checks, and chin). Change from Baseline at Week 12 was calculated as the value at Week 12 minus the value at Baseline. | Baseline (Week 0/Day 1) and Week 12 | 
| Number of Participants With a Minimum 2-grade (G) Improvement in the Investigator Static Global Assessment (ISGA) Score From Baseline at Week 12 | Investigators evaluated the acne severity (S) of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than rare papules; 2=mild S: >G 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate S: >G 2, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: greater than G 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe: many NILs and ILs and more than a few NLs, may have cystic lesions. | Baseline (Week 0/Day 1) and Week 12 | 
| Number of Participants With an ISGA Score of 0 or 1 at Week 12 | Investigators evaluated the acne severity (S) of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than rare papules; 2=mild S: >G 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate S: >G 2, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: greater than G 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe: many NILs and ILs and more than a few NLs, may have cystic lesions. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in LC From Baseline at Weeks 2, 4, 8, and 12 | LC: count of all ILs (i.e., papules, pustules, and nodules) and NILs (i.e., open and closed comedones) at Baseline and at Week 12. TLs were calculated as the sum of ILs and NILs. LC was confined to the face (including forehead, nose, checks, and chin). Percent change from Baseline in LC at Weeks 2, 4, 8, and12 was calculated as the (Week 2/4/8/12 value minus the baseline value divided by baseline value) x 100. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Absolute Change From Baseline in LC at Weeks 2, 4, and 8 | LC: count of all ILs (i.e., papules, pustules, and nodules) and NILs (i.e., open and closed comedones) at Baseline and at Week 12. TLs were calculated as the sum of ILs and NILs. LC was confined to the face (including forehead, nose, checks, and chin). Change from Baseline at Week 12 was calculated as the value at Week 12 minus the value at Baseline. Calculation was based on last observation carried forward (LOCF) imputation method for missing data. | Baseline (Week 0/Day 1); Weeks 2, 4, and 8 | 
| Time to a 50 Percent Reduction in Total Lesion Counts (TLC) | Time to a 50 percent reduction in TLC (sum of ILs and NILs) was the time difference between Baseline and the time to 50 percent reduction in LC. Participants who did not have a >=50 percent reduction from Baseline in TLC during the study were censored at their last visit date. | Baseline (Week 0/Day 1) to Week 12 | 
| Number of Participants With a Minimum 2 G Improvement in ISGA Score at Weeks 2, 4, and 8 | Investigators evaluated the acne severity (S) of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than rare papules; 2=mild S: >G 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate S: >G 2, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: greater than G 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe: many NILs and ILs and more than a few NLs, may have cystic lesions. | Baseline (Week 0/Day 1); Weeks 2, 4, and 8 | 
| Number of Participants With an ISGA Score of 0 or 1 at Weeks 2, 4, and 8 | Investigators evaluated the acne severity (S) of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than rare papules; 2=mild S: >G 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate S: >G 2, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: greater than G 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe: many NILs and ILs and more than a few NLs, may have cystic lesions. | Weeks 2, 4, and 8 | 
| Number of Participants With a Subject's Global Assessment (SGA) Score of 0 or 1 at Weeks 2, 4, 8, and 12 | An SGA of the facial skin, excluding the scalp, was performed by participants using a rating scale of 0 to 4: 0=face is basically free of acne, with only an occasional blackhead (Bh) and/or whitehead (Wh); 1=face has several Bhs and/or Whs and small pimples (P), but there are no tender deep-seated bumps or cysts (DSBCs); 2=face has several to many Bhs and/or Whs and small- to medium-sized P, and may have one DSBC; 3=face has many Bhs and/or Whs, many medium- to large-sized P, and perhaps a few DSBCs; 4=face has Bhs and/or Whs, and several to many medium- to large-sized Ps and DSBCs dominate. | Weeks 2, 4, 8, and 12 | 
| Number of Participants With a 2-G Improvement in ISGA Score and an ISGA Score of 0 or 1 at Weeks 2, 4, 8, and 12 | Investigators evaluated the acne severity (S) of the participants' face using the ISGA scale, ranging from 0 to 5: 0=clear skin with no ILs or NILs; 1=almost clear: rare NIL with no more than rare papules; 2=mild S: >G 1, some NILs with no more than a few ILs (papules/pustules only, no nodular lesions [NLs]); 3=moderate S: >G 2, up to many NILs and may have some ILs, but no more than one small NL; 4=severe: greater than G 3, up to many NILs and ILs, but no more than a few NLs; 5=very severe: many NILs and ILs and more than a few NLs, may have cystic lesions. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Absolute Change in Papule Count From Baseline at Weeks 2, 4, 8, and 12 | A papule is a circumscribed, solid elevation of the skin with no visible fluid. Change from basline in papule count at Weeks 2, 4, 8, and 12 was calculated as the papule count at Week 2/4/8/12 minus the papule count at Baseline. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Absolute Change in Pustule Count From Baseline at Weeks 2, 4, 8, and 12 | A pustule is a small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells. Change from basline in pustule count at Weeks 2, 4, 8, and 12 was calculated as the pustule count at Week 2/4/8/12 minus the pustule count at Baseline. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Absolute Change in Nodule Count From Baseline at Weeks 2, 4, 8, and 12 | A nodule is a slightly elevated lesion on or in the skin. Change from basline in nodule count at Weeks 2, 4, 8, and 12 was calculated as the nodule count at Week 2/4/8/12 value (s) minus the nodule count at Baseline. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Absolute Change in Open Comedone Count From Baseline at Weeks 2, 4, 8, and 12 | An open comedone is a yellow or blackish bump or plug on the skin. Change from Baseline in open comedone count at Weeks 2, 4, 8, and 12 was calculated as the open comedone count at Week 2/4/8/12 minus the open comedone count at Baseline. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Absolute Change in Closed Comedone Count From Baseline at Weeks 2, 4, 8, and 12 | A closed comedone is a whitehead. Change from basline in closed comedone count at Weeks 2, 4, 8, and 12 was calculated as the closed comedone count at Week 2/4/8/12 minus the closed comedone count at Baseline. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Change in Dermatology Life Quality Index (DLQI) Score From Baseline at Weeks 2, 4, 8, and 12 in Participants 17 Years of Age or Older | The DLQI was used to measure how much the participants' skin problem had affected their life over the last week. The DLQI total score ranges from 0 to 30: 0-1=no effect at all on the participant's life; 2-5=small effect on the participant's life; 6-10=moderate effect on the participant's life; 11-20=very large effect on the participant's life; 21-30=extremely large effect on the participant's life. A lower score on the DLQI indicates increased quality of life; therefore, negative changes from Baseline indicate improvements. | Baseline (Week 0/Day 1); Weeks 2, 4, 8, and 12 | 
| Change in Children's Dermatology Life Quality Index (CDLQI) From Baseline at Week 2, 4, 8 and 12 in Participant's With 16 Years Old or Younger | The CDLQI was used to measure how much the participants' skin problem had affected their life over the last week. The CDLQI total score ranges from 0 to 30: 0-1=no effect at all on the participant's life; 2-6=small effect on the participant's life; 7-12=moderate effect on the participant's life; 13-18=very large effect on the participant's life; 19-30=extremely large effect on the participant's life. A lower score on the CDLQI indicates increased quality of life; therefore, negative changes from Baseline indicate improvements. | Baseline (Week 0/Day 1); Week 2, 4, 8, and 12 | 
| Number of Participants With the Indicated Local Tolerability Assessment for Erythema as Evaluated by the Investigator | Erythema is a skin condition characterized by redness or rash. Local tolerability assessments were performed by the Investigator at each study visit and were graded based on severity as G0 to G4: G0=absent (no redness); G1=slight (faint red or pink coloration, barely perceptible); G2=mild (light red or pink coloration); G3=moderate (medium red coloration); G4=severe (beet red coloration). Maximum During Treatment is defined as the maximum severity of erythema reported at any time during treatment. | Baseline (Week 0/Day 1) to Week 12 | 
| Number of Participants With the Indicated Local Tolerability Assessment for Drying as Evaluated by the Investigator | Dryness=skin epidermis that lacks moisture/sebum. Local tolerability assessments were performed by the Investigator at each study visit and were graded based on severity as G0 to G4. G0=absent (none); G1=slight (barely perceptible dryness with no flakes or fissure formation); G2=mild (easily perceptible dryness with no flakes or fissure formation); G3=moderate (easily noted dryness and flakes but no fissure formation); G4=severe (easily noted dryness with flakes and fissure formation). Maximum During Treatment is defined as the maximum severity of dryness reported at any time during treatment. | Baseline (Week 0/Day 1) to Week 12 | 
| Number of Participants With the Indicated Local Tolerability Assessment for Peeling as Evaluated by the Investigator | Peeling skin: damage to and loss of the upper layer of skin (epidermis). Local tolerability assessments for peeling were performed by the Investigator at each study visit and were graded based on severity as G0 to G4: G0=absent (no peeling); G1=slight (mild localized peeling); G2=mild (mild and diffuse peeling); G3=moderate (moderate and diffuse peeling); G4=severe (moderate to prominent, dense peeling). Maximum During Treatment is defined as the maximum severity of peeling reported at any time during treatment. | Baseline (Week 0/Day 1) to Week 12 | 
| Number of Participants With the Indicated Local Tolerability Assessment for Itching as Evaluated by the Participants | Itching is a sensation that causes the desire or reflex to scratch. Local tolerability assessments for itching were performed by the participant at each study visit and were graded based on severity as G0 to G3. G0=none; G1=slight; G2=moderate; G3=strong. Maximum During Treatment is defined as the maximum severity of itching reported at any time during treatment. | Baseline (Week 0/Day 1) to Week 12 | 
| Number of Participants With the Indicated Local Tolerability Assessment for Burning/Stinging as Evaluated by the Participants | Burning/stinging is a pain and burning sensation. Local tolerability assessments were performed by the participant at each study visit based on severity as G0 to G3: G0=none; G1=slight; G2=moderate; G3=strong. Maximum During Treatment is defined as the maximum severity of burning/stinging reported at any time during treatment. | Baseline (Week 0/Day 1) to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acne