Oracea Soolantra Association in Participants With Severe Rosacea

Percent change from baseline in inflammatory lesion count at week 12 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (that is \[i.e.\] papules and pustules) which were defined as follows: Papule - a small, solid elevation less than 1.0 centimeter (cm) in diameter; and Pustule - a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions.

Time frame: Baseline, Week 12

Population: Intent-to-treat (ITT) population consisted of the entire population enrolled and randomized. The last observation carried forward (LOCF) method was used to impute missing values for inflammatory lesion count.

The evaluator assessed the participant's diffuse persistent facial erythema of rosacea by performing a static (snap shot) evaluation of erythema severity at a social distance of approximately 50 centimeter (cm) using CEA scale, at each visit. CEA is a 5 point scale where 0 = clear (clear skin with no signs of erythema); 1 = almost clear (almost clear; slight redness); 2 = mild (mild erythema; definite redness); 3 = moderate (moderate erythema; marked redness); 4 = severe (severe erythema; fiery redness). A higher score than baseline indicates a worse outcome.

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

DLQI focuses on impact of dermatological diseases on quality of life. It is a 10-item validated quality-of-life questionnaire specific to dermatological conditions. 1) how itchy, sore, painful, stinging?, 2) how embarrassed/self-conscious?, 3) interfere shopping or looking after home or garden?, 4) Influence clothes?, 5) affect social/leisure activity?, 6) difficult to do sport?, 7) prevent from working/studying? or If no, problem at work/studying?, 8) problem with partner or close friend?, 9) cause sexual difficulties?, 10) problem caused by treatment?. Total score ranged from 0-30 (each question had a score range of 0- 3) where, 0-1=no effect at all on life; 2-5=small effect on life; 6-10=moderate effect on life; 11- 20=very large effect on life; 21-30=extremely large effect on life. A higher score indicates a low quality of life due to more severe disease.

Time frame: Week 12 (last visit/early termination)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

EQ-5D-5L is a 5-level, 5-dimensional format standardized instrument for use as a measure of health outcome used to assess the impact of study treatments on participants quality of life as follows: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression. Each dimension comprised of 5 levels with corresponding numeric scores, where 1 indicated no problems, and 5 indicated extreme problems. Participant selected answer for each of 5 dimensions considering response that best matches his/her health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). An increase in the EQ-5D-5L total score indicates improvement.

Time frame: Week 12/Last visit or early termination visit

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Participants were evaluated for his/her improvement in rosacea compared to his/her rosacea condition before study, using global Improvement scale. It is a 7 item scale where, 0=complete improvement (all signs and symptoms of disease have resolved \[100% improvement\]); 1=excellent improvement (nearly all signs and symptoms cleared \[90% improvement\]. Only minimal residual signs and symptoms remain); 2=very good improvement (majority of the signs and symptoms have resolved \[about 75% improvement\]); 3=good improvement (significant improvement, but many signs and symptoms remain \[about 50% improvement\]); 4=minimal improvement (slight overall improvement, but not clinically significant \[about 25% improvement\]); 5=no change (overall severity similar to baseline); 6=worse (worse than baseline).

Time frame: Week 12 (last visit/early termination)

Population: ITT population consisted of the entire population enrolled and randomized. Here the over all number of participants analyzed signifies participants who were evaluable for this outcome measure.

The evaluator assessed the participant's rosacea by performing a static (snap shot) evaluation, at a social distance of approximately 50 cm, using the IGA score. IGA is a 5 point scale where, 0 = clear (no inflammatory lesions present, no erythema); 1 = almost clear (very small papules/pustules, very mild erythema present); 2 = mild (few small papules/pustules, mild erythema); 3 = moderate (severe small or large papules/pustules, moderate erythema); 4 = severe (numerous small and/or large papules/pustules, severe erythema).

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily had a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE was any untoward medical occurrence that at any dose: results in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.

Time frame: From the signing of the informed consent form (ICF) up to Week 12

Population: Safety population (all participants treated \[APT\]) - consisted of the ITT population, after exclusion of participants who never used the treatment with certainty based on monitoring report.

The evaluator assessed the participant's diffuse persistent facial erythema of rosacea by performing a static (snap shot) evaluation of erythema severity at a social distance of approximately 50 centimeter (cm) using CEA scale, at each visit. CEA is a 5 point scale where 0 = clear (clear skin with no signs of erythema); 1 = almost clear (almost clear; slight redness); 2 = mild (mild erythema; definite redness); 3 = moderate (moderate erythema; marked redness); 4 = severe (severe erythema; fiery redness). A higher score than baseline indicates a worse outcome.

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

Impact of study treatments on subjects' quality of life was measured by using DLQI questionnaire. DLQI focuses on impact of dermatological diseases on quality of life. It is a 10-item validated quality-of-life questionnaire specific to dermatological conditions. 1) how itchy, sore, painful, stinging?, 2) how embarrassed/self-conscious?, 3) interfere shopping or looking after home or garden?, 4) Influence clothes?, 5) affect social/leisure activity?, 6) difficult to do sport?, 7) prevent from working/studying? or If no, problem at work/studying?, 8) problem with partner or close friend?, 9) cause sexual difficulties?, 10) problem caused by treatment?. Total score ranged from 0-30 (each question had a score range of 0- 3) where, 0-1=no effect at all on life; 2-5=small effect on life; 6-10=moderate effect on life; 11- 20=very large effect on life; 21-30=extremely large effect on life. A higher score indicates a low quality of life due to more severe disease.

Time frame: Baseline, Week 12 (last visit/early termination)

Population: ITT population consisted of the entire population enrolled and randomized. Here, n, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

EQ-5D-5L is a 5-level, 5-dimensional format standardized instrument for use as a measure of health outcome used to assess the impact of study treatments on participants quality of life as follows: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression. Each dimension comprised of 5 levels with corresponding numeric scores, where 1 indicated no problems, and 5 indicated extreme problems. Participant selected answer for each of 5 dimensions considering response that best matches his/her health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). An increase in the EQ-5D-5L total score indicates improvement.

Time frame: Baseline, Week 12 (last visit/early termination)

Population: ITT population consisted of the entire population enrolled and randomized. Here, n, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Participants were to evaluated for his/her improvement in rosacea compared to his/her rosacea condition before study, using global Improvement scale. it is a 7 item scale where, 0=complete improvement (all signs and symptoms of disease have resolved \[100% improvement\]); 1=excellent improvement (nearly all signs and symptoms cleared \[90% improvement\]. Only minimal residual signs and symptoms remain); 2=very good improvement (majority of the signs and symptoms have resolved \[about 75% improvement\]); 3=good improvement (significant improvement, but many signs and symptoms remain \[about 50% improvement\]); 4=minimal improvement (slight overall improvement, but not clinically significant \[about 25% improvement\]); 5=no change (overall severity similar to baseline); 6=worse (worse than baseline). .

Time frame: Week 12 (last visit/early termination)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

The evaluator assessed the participant's rosacea by performing a static (snap shot) evaluation, at a social distance of approximately 50 cm, using the IGA score. IGA is a 5 point scale where, 0 = clear (no inflammatory lesions present, no erythema); 1 = almost clear (very small papules/pustules, very mild erythema present); 2 = mild (few small papules/pustules, mild erythema); 3 = moderate (severe small or large papules/pustules, moderate erythema); 4 = severe (numerous small and/or large papules/pustules, severe erythema).

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

The evaluator recorded the severity of the participant's facial stinging/burning sensation during the last 24 hours according to the stinging/burning scale. Stinging/burning scale is a 4 point scale where, 0 = none (No stinging/burning ); 1 = mild (slight warm, tingling/stinging sensation, not really bothersome); 2 = moderate (definite warm, tingling/stinging sensation that is somewhat bothersome); 3 = severe (hot, tingling/stinging sensation that has caused definite discomfort).

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.

WPAI:GH questionnaire was an instrument to measure impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement. Currently Employed question was assessed in this outcome measure.

Time frame: Week 12 (Last visit/early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Subject's satisfaction questionnaire was used to specifically collect the subjects' feedback on the treatment regimen, the level of satisfaction and future usage. Questionnaire consisted of 4 parts: Part A, B, C and D. where Part A consisted of following 12 questions about study drugs (capsules and cream): 1-Time the study regimen took to work, 2-Improvement of facial lesions, 3-Improvement of facial redness, 4-Improvement of ocular symptoms, 5-Improvement of flushing episodes, 6-How bothered by side effects, 7-Your face looks, 8-You feel, 9-Easy to incorporate in daily routine, 10-Using the study regimen again, 11-Overall satisfaction, 12-Compared to last treatment. Satisfied score of questionnaire meant as participants responded as Very satisfied (Questions-1,2,3,4,5,11), Not bothered at all (Question-6), A lot better (Questions- 7,8,12), yes (Question-10), strongly agree (Question-9).

Time frame: Week 12 (Last visit/early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Part B of Questionnaire consisted of following 10 questions about both provided skin care products cleanser and moisturizer: 1-Easy to incorporate into a daily routine, 2-Recommend to my family or friends, 3-Help my skin look healthier, 4-More confident with rosacea, 5-More confident with skin appearance, 6-Positive difference in the appearance, 7-Keep using both skin care products, 8-Make my skin more hydrated, 9-Improve the texture of my skin, 10-Pleasant to use.

Time frame: Week 12 (Last visit/early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Part C subject satisfaction questionnaire consisted of following 4 questions about the cosmetic product cleanser: 1-Clean healthy skin feeling, 2-Deep cleansing without stripping moisture, 3-Rinsed off easily, 4-Not make my skin feel tight or dry.

Time frame: Week 12 (Last visit or early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Part D of subject satisfaction questionnaire consisted of following 4 questions about the cosmetic product moisturizer: 1-Skin feel soft and smooth, 2-Improve my skin moisture, 3-Leave my skin hydrated and protected, 4-Provide comforting sensation.

Time frame: Week 12 (Last visit/early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Percentage of participants with 100% reduction in inflammatory lesions at Weeks 4, 8 and 12 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (i.e. papules and pustules) which were defined as follows: Papule - a small, solid elevation less than 1.0 centimeter in diameter. Pustule - a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions.

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

Percentage of participants with clear inflammatory lesions at week 12 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (i.e. papules and pustules) which were defined as follows: Papule - a small, solid elevation less than 1.0 cm in diameter. Pustule - a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions.

Time frame: Week 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

Percent Change from Baseline in Dermatology Life Quality Index questionnaire Total Score at Last Visit. DLQI focuses on impact of dermatological diseases on quality of life. It is a 10-item validated quality-of life questionnaire specific to dermatological conditions. 1) how itchy, sore, painful, stinging?, 2) how embarrassed/self-conscious?, 3) interfere shopping or looking after home or garden?, 4) Influence clothes?, 5) affect social/leisure activity?, 6) difficult to do sport?, 7) prevent from working/studying? or If no, problem at work/studying?, 8) problem with partner or close friend?, 9) cause sexual difficulties?, 10) problem caused by treatment?. Total score ranged from 0-30 (each question had a score range of 0-3) where, 0-1=no effect at all on life; 2-5=small effect on life; 6-10=moderate effect on life; 11- 20=very large effect on life; 21-30=extremely large effect on life. A higher score indicates a low quality of life due to more severe disease.

Time frame: Baseline, Week 12 (last visit/early termination)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Percent change from baseline in inflammatory lesion count at Weeks 4 and 8 was reported. Inflammatory lesions included facial inflammatory lesions of rosacea (i.e. papules and pustules) which were defined as follows: Papule - a small, solid elevation less than 1.0 centimeter in diameter. Pustule - a small, circumscribed elevation of the skin, which contains yellow white exudates. Papules and pustules were counted separately on each of the 5 facial regions (forehead, chin, nose, right cheek and left cheek). Notably, nodules (i.e. circumscribed, elevated, solid lesions more than 1.0 cm in diameter with palpable depth) were not included in the count of inflammatory lesions.

Time frame: Baseline, Weeks 4 and 8

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values for inflammatory lesion count.

The evaluator recorded the severity of the participant's facial stinging/burning sensation during the last 24 hours according to the stinging/burning scale. Stinging/burning scale is a 4 point scale where, 0 = none (No stinging/burning ); 1 = mild (slight warm, tingling/stinging sensation, not really bothersome); 2 = moderate (definite warm, tingling/stinging sensation that is somewhat bothersome); 3 = severe (hot, tingling/stinging sensation that has caused definite discomfort).

Time frame: Weeks 4, 8 and 12

Population: ITT population consisted of the entire population enrolled and randomized. The LOCF method was used to impute missing values.

WPAI:GH questionnaire is an instrument to measure impairment in both paid and unpaid work during the past week including questions: missed hours from work because of rosacea?, missed hours from work because of other reason?, number of Working hours. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement.

Time frame: Week 12 (Last visit/Early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

WPAI:GH questionnaire is an instrument to measure impairment in both paid and unpaid work during the past week, on a scale ranging from 0 (health problems had no effect) to 10 (health problems completely prevented them from working) including questions: 5) how much rosacea affect productivity at work?; 6) how much rosacea affect daily activity?. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Low scores indicated little or no impact of health problems on work and activities, and a negative change in the WPAI score indicated improvement.

Time frame: Week 12 (Last visit/Early termination visit)

Population: ITT population consisted of the entire population enrolled and randomized. Here the overall number of participants analyzed signifies participants who were evaluable for this outcome measure.