Study Identification Unique Protocol ID: 1922-201-002 Brief Title: Phase 2 A Safety and Efficacy Study of Setipiprant Tablets in Androgenetic Alopecia in Males Official Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2A Study of Setipiprant Tablets in Androgenetic Alopecia in Males With a Comparator Arm Secondary IDs:

Study Status Record Verification: May 2016 March 2019 Overall Status: Not yet recruiting Completed Study Start: June 2016 July 14, 2016 Primary Completion: July 2017 [Anticipated] March 15, 2018 [Actual] Study Completion: September 2017 [Anticipated] May 22, 2018 [Actual] First Submitted: May 20, 2016 First Submitted that

Met QC Criteria: May 20, 2016 First Posted: May 24, 2016 [Estimate] Results First Submitted: March 15, 2019 Results First Submitted that

Met QC Criteria: March 15, 2019 Results First Posted: April 5, 2019 [Actual] Last Update Submitted that

Met QC Criteria: May 20, 2016 March 15, 2019 Last Update Posted: May 24, 2016 [Estimate] April 5, 2019 [Actual]

Oversight U.S. FDA-regulated Drug: Yes U.S. FDA-regulated Device: No Data Monitoring: No

Study Description Brief Summary: This study will evaluate the safety, tolerability and efficacy of the oral administration of setipiprant tablets 1000 mg twice daily (BID) relative to placebo and active comparator, finasteride 1 mg once daily, in 18 to 41 49 years old males with androgenetic alopecia (AGA). Detailed Description:

Conditions Conditions: Alopecia Keywords:

Study Design Study Type: Interventional Primary Purpose: Treatment Study Phase: Phase 2 Interventional Study Model: Parallel Assignment Number of Arms: 3 Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Allocation: Randomized Enrollment: 187 [Anticipated] 169 [Actual]

Arms and Interventions Arms Assigned Interventions Experimental: Setipiprant Setipiprant 1000 mg setipiprant ( two 2 X 500 mg ) tablets ) twice daily ( , orally, BID ) at 12-hour intervals for 24 weeks. Drug: Setipiprant Two 500 mg Setipiprant tablets , orally, BID for 24 weeks . KYTH-105

AGN-241679 Other Names: Placebo Comparator: Placebo Two placebo tablets BID at 12-hour intervals for 24 weeks. Drug: Placebo Two Placebo tablets , orally, BID for 24 weeks . Active Comparator: Finasteride Finasteride 1 mg tablet, orally, once daily for 24 weeks. Drug: Finasteride Finasteride tablet, orally, once daily for 24 weeks. Active Comparator: Finasteride 1 mg finasteride tablet once daily for 24 weeks. Drug: finasteride Finasteride tablet once daily.

Eligibility Minimum Age: 18 Years Maximum Age: 41 49 Years Sex: Male Gender Based: Yes Androgenetic Alopecia in Males Accepts Healthy Volunteers: No Criteria: Inclusion Criteria: Participant has androgenetic alopecia (AGA)

Participant agrees to maintain current hair care regimen, refraining from hair weaving, hair colorants or dyes and non-study hair growth products during the study. Exclusion Criteria: History of hair loss for reasons other than AGA

Scarring of the scalp or any condition or disease of the scalp, hair or hair shaft

Use of products within 6 months of study start used continuously for at least 1 month that could impact hair growth

Hair-weaving within 6 months

Use of hair colorants or dyes within 6 months.

IPDSharing Plan to Share IPD:

References Citations: Links:

URL: http://www.allerganclinicaltrials.com More Information

Available IPD/Information:

Documents Study Protocol

Document Date: February 17, 2017

Uploaded: 03/15/2019 18:22

Prot_000.pdf File Name:

Statistical Analysis Plan

Document Date: July 25, 2018

Uploaded: 03/15/2019 18:22

SAP_001.pdf File Name:



Study Results

Participant Flow Reporting Groups Description Placebo Two placebo tablets, twice daily (BID) at 12-hour intervals for 24 weeks. Setipiprant Setipiprant 1000 mg (2 X 500 mg) tablets, orally, BID at 12-hour intervals for 24 weeks. Finasteride Finasteride 1 mg tablet, orally, once daily for 24 weeks. Overall Study Placebo Setipiprant Finasteride Started 74 83 12 Safety Population (Treated) 73 81 12 mITT Population 70 78 11 Completed 48 57 8 Not Completed 26 26 4 Adverse Event 2 6 1 Withdrawal of Consent 11 12 2 Lost to Follow-up 11 8 1 Non-Compliance with Study Drug 2 0 0

Baseline Characteristics Baseline Analysis Population Description Modified Intent-to-Treat (mITT) population included all randomized participants who received study intervention in the study and had a baseline and at least 1 postbaseline measurement for one of the coprimary efficacy measures. Reporting Groups Description Placebo Two placebo tablets BID at 12-hour intervals for 24 weeks. Setipiprant Setipiprant 1000 mg (2 X 500 mg) tablets, orally, BID at 12-hour intervals for 24 weeks. Finasteride Finasteride 1 mg tablet, orally, once daily for 24 weeks. Baseline Measures Placebo Setipiprant Finasteride Total Overall Number of Participants 70 78 11 159 Age, Continuous Measure type: Mean ( Standard Deviation ) Unit of measure: years Number Analyzed 70 Participants 78 Participants 11 Participants 159 Participants 36.9 (6.08) 36.3 (6.69) 34.1 (3.05) 36.4 (6.25) Sex/Gender, Customized Measure type: Count of Participants Unit of measure: Participants Number Analyzed 70 Participants 78 Participants 11 Participants 159 Participants Male 70 100% 78 100% 11 100% 159 100% Race/Ethnicity, Customized Measure type: Count of Participants Unit of measure: Participants Number Analyzed 70 Participants 78 Participants 11 Participants 159 Participants White 59 84.29% 70 89.74% 9 81.82% 138 86.79% Black or African American 4 5.71% 3 3.85% 0 0% 7 4.4% Asian 4 5.71% 1 1.28% 1 9.09% 6 3.77% American Indian or Alaska Native 0 0% 0 0% 1 9.09% 1 0.63% Native Hawaiian or Other Pacific Islander 2 2.86% 1 1.28% 0 0% 3 1.89% Other 1 1.43% 2 2.56% 0 0% 3 1.89% Missing 0 0% 1 1.28% 0 0% 1 0.63% Race/Ethnicity, Customized Measure type: Count of Participants Unit of measure: Participants Number Analyzed 70 Participants 78 Participants 11 Participants 159 Participants Hispanic 6 8.57% 8 10.26% 0 0% 14 8.81% Non-hispanic 64 91.43% 70 89.74% 11 100% 145 91.19% Target Area Hair Count (TAHC) Within Left 1 cm^2 Circular Area Measure type: Mean ( Standard Deviation ) Unit of measure: terminal hairs/cm^2 Number Analyzed 70 Participants 78 Participants 11 Participants 159 Participants 136.7 (55.81) 148.6 (64.58) 139.9 (47.72) 142.8 (59.67) Measure Description: TAHC was measured using digital imaging analysis (macrophotographs) and was reported in terminal hairs/centimeters squared (cm^2). It is a standardized objective quantification of number of hairs within a prespecified target area of scalp at different timepoints. Target area used to count TAHC was 1 cm^2 circular area of clipped hair located at anterior leading edge of vertex thinning area of scalp and centered with a semi-permanent microdot tattoo to ensure same target area was reproduced at each visit. Measure Analysis Population Description: Participants from mITT with data available for analysis at the given timepoint.

Outcome Measures 1. Primary Outcome Measure: Measure Title Change From Baseline in Target Area Hair Count (TAHC) at Week 24 Measure Description TAHC was measured using digital imaging analysis and was reported in terminal hairs/centimeters square (cm^2). TAHC is a standardized objective quantification of the number of hairs within a prespecified target area of the scalp at different timepoints, using macrophotography digital images. The total number of terminal hairs (hair width ≥ 30 μm) was calculated from macrophotographs. The target area used to count TAHC was a 1 cm^2 circular area of clipped hair (length approximately 1 mm) located at the anterior leading edge of the vertex thinning area of the scalp and centered with a semi-permanent microdot tattoo to ensure the same target area was reproduced at each visit. A positive change from Baseline indicated improvement (increase in the number of terminal hairs). Missing data are imputed up to Week 24 using last observation carried forward (LOCF) method. Time Frame Baseline (Day 1) to Week 24 Analysis Population Description mITT population included all randomized participants who received study intervention and had a baseline and at least 1 postbaseline measurement for 1 of the coprimary efficacy measures. As per protocol Amendment 1, Finasteride arm group was not included in the analysis model. Number analyzed is participants with data available for analysis. Reporting Groups Description Placebo Two placebo tablets BID at 12-hour intervals for 24 weeks. Setipiprant Setipiprant 1000 mg (2 X 500 mg) tablets, orally, BID at 12-hour intervals for 24 weeks. Measured Values Placebo Setipiprant Overall Number of Participants Analyzed 61 70 Change From Baseline in Target Area Hair Count (TAHC) at Week 24 Measure Type: Least Squares Mean (Standard Error) Unit of Measure: terminal hairs/cm^2 6.7 (3.25) 7.1 (3.03) Statistical Analysis 1 for Change From Baseline in Target Area Hair Count (TAHC) at Week 24 Statistical Analysis Overview Comparison Groups Placebo , Setipiprant Comments [Not specified] Type of Statistical Test Superiority Comments [Not specified] Statistical Test of Hypothesis P-Value 0.9239 Comments P-values were from analysis of covariance (ANCOVA) model including fixed effects of treatment, and covariates of age and baseline TAHC value, with the Type III sum of squares. Method ANCOVA Comments [Not specified] Method of Estimation Estimation Parameter Least-squares Mean Difference Estimated Value 0.4 Confidence Interval (2-sided) 95 % -8.38 to 9.23 Parameter Dispersion Type: Standard Error of the Mean Value: 4.45 Estimation Comments [Not specified] 2. Primary Outcome Measure: Measure Title Subject Self-Assessment (SSA) Score in Hair Growth at Week 24 Measure Description The SSA consisted of a single-item measure that assesses each participant's perception of change in scalp hair growth. The participant used a standardized global photograph of his scalp taken at the Screening visit presented side by side with a standardized global photograph taken at the postbaseline visit to give a comparative score. The photographs were presented in a blinded and randomized manner to avoid influencing the participant, and response options were on a 7-point ordinal scale (where, -3=Greatly decreased, -2=Moderately decreased, -1=Slightly decreased, 0=No change, +1=Slightly increased, +2=Moderately increased and +3=Greatly increased). The higher the mean SSA value, the more the perception of hair growth from baseline. Missing data are imputed up to Week 24 using LOCF method. Time Frame Week 24 Analysis Population Description mITT population included all randomized participants who received study intervention and had a baseline and at least 1 postbaseline measurement for 1 of the coprimary efficacy measures. As per protocol Amendment 1, Finasteride arm group was not included in the analysis model. Number analyzed is participants with data available for analysis. Reporting Groups Description Placebo Two placebo tablets BID at 12-hour intervals for 24 weeks. Setipiprant Setipiprant 1000 mg (2 X 500 mg) tablets, orally, BID at 12-hour intervals for 24 weeks. Measured Values Placebo Setipiprant Overall Number of Participants Analyzed 68 78 Subject Self-Assessment (SSA) Score in Hair Growth at Week 24 Measure Type: Least Squares Mean (Standard Error) Unit of Measure: score on a scale -0.2 (0.15) -0.3 (0.14) Statistical Analysis 1 for Subject Self-Assessment (SSA) Score in Hair Growth at Week 24 Statistical Analysis Overview Comparison Groups Placebo , Setipiprant Comments [Not specified] Type of Statistical Test Superiority Comments [Not specified] Statistical Test of Hypothesis P-Value 0.9101 Comments P-values were from analysis of covariance (ANCOVA) model including fixed effects of treatment, and covariates of age, with the Type III sum of squares. Method ANCOVA Comments [Not specified] Method of Estimation Estimation Parameter Least-squares Mean Difference Estimated Value 0.0 Confidence Interval (2-sided) 95 % -0.42 to 0.37 Parameter Dispersion Type: Standard Error of the Mean Value: 0.20 Estimation Comments [Not specified]

Reported Adverse Events Time Frame From first dose of study drug up to 8 weeks post last dose (Up to 32 weeks) Adverse Event Reporting Description Safety population included all the participants who received at least 1 dose of study intervention. Reporting Groups Description Placebo Two placebo tablets BID at 12-hour intervals for 24 weeks. Setipiprant Setipiprant 1000 mg (2 X 500 mg) tablets, orally, BID at 12-hour intervals for 24 weeks. Finasteride Finasteride 1 mg tablet, orally, once daily for 24 weeks. All-Cause Mortality Placebo Setipiprant Finasteride Affected/ At Risk (%) Affected/ At Risk (%) Affected/ At Risk (%) Total 0 / 73 ( 0% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Serious Adverse Events Placebo Setipiprant Finasteride Affected/ At Risk (%) Affected/ At Risk (%) Affected/ At Risk (%) Total 2 / 73 ( 2.74% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Infections and infestations Cellulitis A† 1 / 73 ( 1.37% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Nervous system disorders Multiple sclerosis A† 1 / 73 ( 1.37% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) † Indicates events were collected by systematic assessment.

A Term from vocabulary, MedDRA 21.0

Other Adverse Events

Frequency Threshold Above Which Other Adverse Events are Reported: 2 % Placebo Setipiprant Finasteride Affected/ At Risk (%) Affected/ At Risk (%) Affected/ At Risk (%) Total 26 / 73 ( 35.62% ) 28 / 81 ( 34.57% ) 6 / 12 ( 50% ) Gastrointestinal disorders Abdominal pain A† 1 / 73 ( 1.37% ) 3 / 81 ( 3.7% ) 0 / 12 ( 0% ) Abdominal pain upper A† 0 / 73 ( 0% ) 2 / 81 ( 2.47% ) 0 / 12 ( 0% ) Constipation A† 2 / 73 ( 2.74% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Diarrhoea A† 2 / 73 ( 2.74% ) 4 / 81 ( 4.94% ) 1 / 12 ( 8.33% ) Nausea A† 3 / 73 ( 4.11% ) 1 / 81 ( 1.23% ) 0 / 12 ( 0% ) Vomiting A† 0 / 73 ( 0% ) 1 / 81 ( 1.23% ) 1 / 12 ( 8.33% ) General disorders Fatigue A† 1 / 73 ( 1.37% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Immune system disorders Skin abrasion A† 0 / 73 ( 0% ) 1 / 81 ( 1.23% ) 1 / 12 ( 8.33% ) Infections and infestations Bronchitis A† 1 / 73 ( 1.37% ) 2 / 81 ( 2.47% ) 0 / 12 ( 0% ) Gastroenteritis A† 1 / 73 ( 1.37% ) 2 / 81 ( 2.47% ) 0 / 12 ( 0% ) Influenza A† 3 / 73 ( 4.11% ) 1 / 81 ( 1.23% ) 0 / 12 ( 0% ) Nasopharyngitis A† 3 / 73 ( 4.11% ) 3 / 81 ( 3.7% ) 0 / 12 ( 0% ) Sinusitis A† 4 / 73 ( 5.48% ) 3 / 81 ( 3.7% ) 0 / 12 ( 0% ) Upper respiratory tract infection A† 0 / 73 ( 0% ) 6 / 81 ( 7.41% ) 2 / 12 ( 16.67% ) Investigations Alanine aminotransferase increased A† 3 / 73 ( 4.11% ) 4 / 81 ( 4.94% ) 0 / 12 ( 0% ) Aspartate aminotransferase increased A† 2 / 73 ( 2.74% ) 6 / 81 ( 7.41% ) 1 / 12 ( 8.33% ) Blood glucose increased A† 3 / 73 ( 4.11% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Weight increased A† 2 / 73 ( 2.74% ) 4 / 81 ( 4.94% ) 0 / 12 ( 0% ) White blood cell count increased A† 3 / 73 ( 4.11% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Musculoskeletal and connective tissue disorders Arthralgia A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Nervous system disorders Headache A† 1 / 73 ( 1.37% ) 3 / 81 ( 3.7% ) 0 / 12 ( 0% ) Psychiatric disorders Agitation A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Libido decreased A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 2 / 12 ( 16.67% ) Reproductive system and breast disorders Testicular pain A† 2 / 73 ( 2.74% ) 0 / 81 ( 0% ) 0 / 12 ( 0% ) Respiratory, thoracic and mediastinal disorders Dyspnoea A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Oropharyngeal pain A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Tonsillar hypertrophy A† 0 / 73 ( 0% ) 2 / 81 ( 2.47% ) 0 / 12 ( 0% ) Skin and subcutaneous tissue disorders Acne A† 0 / 73 ( 0% ) 2 / 81 ( 2.47% ) 0 / 12 ( 0% ) Hair growth abnormal A† 1 / 73 ( 1.37% ) 3 / 81 ( 3.7% ) 0 / 12 ( 0% ) Pruritus A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Rash generalised A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Swelling face A† 0 / 73 ( 0% ) 0 / 81 ( 0% ) 1 / 12 ( 8.33% ) Vascular disorders Hypertension A† 1 / 73 ( 1.37% ) 2 / 81 ( 2.47% ) 0 / 12 ( 0% ) † Indicates events were collected by systematic assessment.

A Term from vocabulary, MedDRA 21.0



Limitations and Caveats Due to change in planned analysis, data of participants in the finasteride arm group were not included in the efficacy analysis.