Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2A Study of Setipiprant Tablets in Androgenetic Alopecia in Males
Phase: PHASE2
Conditions: Alopecia
Sponsor: Allergan

NCT02781311 
 
Study ID: 1922-201-002  
 
Title: MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PHASE 2A STUDY OF SETIPIPRANT TABLETS IN ANDROGENETIC ALOPECIA IN 
MALES 
 
Protocol Amendment 1 Date: 17‐Feb‐2017 
 
 
 

 
 
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Title Page 
ALLERGAN – CONFIDENTIAL 
The following contains confidential, proprietary information  
which is the property of Allergan 
 
MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 
2A STUDY OF SETIPIPRANT TABLETS IN ANDROGENETIC ALOPECIA IN MALES 
 
 
 
 
Protocol Number:   
1922-201-002 
Phase: 
2A 
Name of Investigational 
Product: 
Setipiprant Tablets 
Sponsor: 
 
Allergan (North America) 
2525 Dupont Drive 
Irvine, California USA 
92612 
+1-714-246-4500 
+1-800-347-4500 
 
 
Emergency Telephone 
Numbers: 
Refer to the Study Contacts Page 
Serious Adverse Event 
Reporting Fax Numbers: 
 
 

 
 
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Allergan Medical Safety 
Physician 
Contact Information: 
 
 
Allergan Signatory: 
 
 
 
Refer to the final page of this protocol for electronic 
signature and date of approval. 
 
The following information can be found on FDA Form 1572 and/or study contacts page:  Name 
and contact information of Allergan study personnel and Emergency Telephone Numbers; name, 
address, and statement of qualifications of each investigator; name of each subinvestigator 
working under the supervision of the investigator; name and address of the research facilities to 
be used; name and address of each reviewing IRB; US 21 CFR 312.23 section 6(iii)b. 
 

 
 
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INVESTIGATOR SIGNATURE PAGE 
INVESTIGATOR: 
 
 
 
 
I agree to: 
• Implement and conduct this study diligently and in strict compliance with the protocol, 
good clinical practices, and all applicable laws and regulations. 
• Maintain all information supplied by the sponsor in confidence and, when this information 
is submitted to an institutional review board (IRB), independent ethics committee (IEC) or 
another group, it will be submitted with a designation that the material is confidential. 
• Ensure that all persons assisting with the trial are adequately informed about the protocol, 
the investigational product(s), and their trial-related duties and functions. 
I have read this protocol in its entirety and I agree to all aspects. 
 
 
 
 
 
Investigator Printed Name 
 
Signature 
 
Date 
 
 

 
 
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Table of Contents 
Table of Contents .............................................................................................................................4 
1. 
Background and Clinical Rationale ........................................................................................15 
2. 
Study Objectives and Clinical Hypotheses .............................................................................17 
2.1 
Study Objectives ...........................................................................................................17 
2.2 
Clinical Hypotheses ......................................................................................................17 
3. 
Study Design ...........................................................................................................................17 
 
 
3.2 
Data Monitoring Committee .........................................................................................18 
4. 
Study Population and Entry Criteria .......................................................................................18 
4.1 
Number of Subjects .......................................................................................................18 
4.2 
Study Population Characteristics ..................................................................................19 
4.3 
Inclusion Criteria ...........................................................................................................19 
4.4 
Exclusion Criteria..........................................................................................................20 
4.5 
Permissible and Prohibited Medications/Treatments ....................................................21 
4.5.1 
Permissible Medications/Treatments ...............................................................21 
4.5.2 
Prohibited Medications/Treatments .................................................................21 
4.5.3 
Special Activities .............................................................................................22 
5. 
Study Treatments ....................................................................................................................22 
5.1 
Study Treatments and Formulations ..............................................................................22 
5.2 
Control Treatments ........................................................................................................23 
5.3 
Methods for Masking/Blinding .....................................................................................23 
5.4 
Treatment Allocation Ratio and Stratification...............................................................23 
5.5 
Method for Assignment to Treatment Groups/Randomization .....................................23 
5.6 
Treatment Regimen and Dosing ....................................................................................24 
5.7 
Storage of Study Drugs .................................................................................................24 
5.8 
Preparation of Study Drugs ...........................................................................................24 
5.9 
Treatment Administration .............................................................................................25 
6. 
Response Measures and Summary of Data Collection Methods ............................................25 
6.1 
Efficacy Measures .........................................................................................................25 
6.1.1 
Primary Efficacy Measures ..............................................................................26 
 
 

 
 
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6.3 
Safety Measures ............................................................................................................31 
6.3.1 
Adverse Events ................................................................................................31 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.4 
Examination Procedures, Tests, Equipment, and Techniques .......................................34 
6.4.1 
Semipermanent Microdot Tattoo .....................................................................34 
6.4.2 
Global Photographs ..........................................................................................34 
6.4.3 
Macrophotography ...........................................................................................35 
6.5 
Summary of Methods of Data Collection .....................................................................35 
6.6 
Other Study Supplies .....................................................................................................36 
7. 
Statistical Procedures ..............................................................................................................37 
7.1 
Analysis Populations .....................................................................................................37 
7.2 
Collection and Derivation of Primary and Other Efficacy Assessments ......................37 
7.2.1 
Primary Efficacy Variables ..............................................................................39 
 
 
7.3 
Hypothesis and Methods of Analysis ............................................................................41 
7.3.1 
Primary Efficacy Analyses ...............................................................................41 
 
 
7.3.3 
Safety Analyses ................................................................................................43 
 
 
7.4 
Other Analyses ..............................................................................................................43 
 
 
7.6 
Interim Analyses............................................................................................................44 
8. 
Study Visit Schedule and Procedures .....................................................................................44 
8.1 
Subject Entry Procedures ..............................................................................................45 
8.1.1 
Overview of Entry Procedures .........................................................................45 
8.1.2 
Informed Consent and Subject Privacy............................................................45 

 
 
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8.3 
Procedures for Final Study Entry ..................................................................................45 
8.4 
Instructions for the Subjects ..........................................................................................46 
8.5 
Unscheduled Visits ........................................................................................................46 
8.6 
Compliance With Protocol ............................................................................................46 
8.7 
Early Discontinuation of Subjects .................................................................................47 
8.8 
Withdrawal Criteria .......................................................................................................47 
8.9 
Study Termination .........................................................................................................47 
9. 
Adverse Events .......................................................................................................................47 
9.1 
Definitions .....................................................................................................................47 
9.1.1 
Adverse Event ..................................................................................................47 
9.1.2 
Serious Adverse Event .....................................................................................48 
9.1.3 
Severity ............................................................................................................49 
9.1.4 
Relationship to Study Drug or Study Procedure ..............................................49 
9.2 
Procedures for Reporting Adverse Events ....................................................................49 
 
 
 
 
10.  Administrative Items ..............................................................................................................50 
10.1  Protection of Human Subjects .......................................................................................51 
10.1.1  Compliance with Informed Consent Regulations (US 21 CFR Part 50) and 
Relevant Country Regulations .........................................................................51 
10.1.2  Compliance With IRB or IEC Regulations ......................................................51 
10.1.3  Compliance With Good Clinical Practice ........................................................51 
10.1.4  Compliance With Electronic Records; Electronic Signatures Regulations 
(US 21CFR Part 11) .........................................................................................51 
10.2  Changes to the Protocol ................................................................................................51 
10.3  Subject Confidentiality .................................................................................................51 
10.3.1  Subject Privacy ................................................................................................52 
10.4  Documentation ..............................................................................................................52 
10.4.1  Source Documents ...........................................................................................52 
10.4.2  Case Report Form Completion ........................................................................53 
10.4.3  Study Summary ................................................................................................54 
10.4.4  Retention of Documentation ............................................................................54 
10.5  Labeling, Packaging, and Return or Disposal of Study drugs/Treatments ...................54 
10.5.1  Labeling/Packaging ..........................................................................................54 

 
 
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10.5.2  Clinical Supply Inventory ................................................................................55 
10.5.3  Return or Disposal of Study Drugs and/or Supplies ........................................55 
10.6  Monitoring by the Sponsor ...........................................................................................55 
 
10.8  Publications ...................................................................................................................56 
10.9  Coordinating Investigator .............................................................................................56 
11.  References ...............................................................................................................................57 
12.  Attachments ............................................................................................................................59 
12.1  Examination Procedures, Tests, Equipment, and Techniques .......................................59 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.2  Safety Measures ............................................................................................................91 
12.3  Glossary of Abbreviations .............................................................................................93 
12.4  Protocol Amendment Summary ....................................................................................95 
 

 
 
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Protocol Summary 
 
Study Compound: Setipiprant, a tetrahydropyridoindole derivative 
Phase: 2a 
Study Objectives  
1) To evaluate the safety, tolerability, and efficacy of oral administration of setipiprant tablets 1000 mg twice daily 
(BID) relative to placebo in males with androgenetic alopecia (AGA) who are 18 to 49 years old and in generally 
good health.  
 
 
Clinical Hypotheses  
• Setipiprant tablets 1000 mg BID have an acceptable safety profile following oral administration for 24 weeks. 
• Setipiprant tablets 1000 mg BID are more effective than placebo in increasing hair growth, as measured by the 
change from baseline in target area hair count (TAHC) in terminal hairs/cm2 using digital image analysis at 
24 weeks after oral administration. 
• Setipiprant tablets 1000 mg BID are more effective than placebo in increasing scalp hair growth, as measured by 
the distribution of the Subject Self-Assessment (SSA) scores using a 7-point scale at 24 weeks after oral 
administration. 
Study Design  
Structure: Multicenter, randomized, double-blind, placebo-controlled study designed to determine the effect of 
treatment with setipiprant tablets 1000 mg BID on scalp hair growth as assessed by objective (ie, imaging-based) 
and subjective (ie, 
 subject-reported) measures.  
Duration: Approximately 32 weeks (enrollment through exit) 
Study Treatment Group: Setipiprant tablets 1000 mg BID 
Control: Placebo BID  
Dosage/Dose Regimen: Setipiprant tablets 1000 mg BID or placebo tablets BID  
Enrollment/Stratification:  
•
 
  
 
 subjects will be randomized in a1:1 ratio to receive setipiprant tablets 1000 mg BID or 
placebo BID, and stratified by baseline age 18 to 34 and 35 to 49 years. 
 
 
Study Population Characteristics 
Number of Subjects: Approximately 187 will be enrolled in up to 20 US sites 
Condition/Disease: Androgenetic alopecia with vertex patterns IIIv, IV, or V as assessed with the Norwood-
Hamilton Hair Loss Scale (NHS) 
Key Inclusion Criteria:  
• Male subjects in generally good health, aged 18 to 49 years (inclusive) 
• Androgenetic alopecia with vertex patterns IIIv, IV, or V on the NHS 
• 
 

 
 
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Key Exclusion Criteria:   
• History or evidence of hair loss for reasons other than AGA  
• Scarring of the scalp or any condition or disease of the scalp, hair, or hair shaft (
 
 
 
Response Measures 
Coprimary Efficacy Measures: change from baseline in TAHC of terminal hairs/cm2 as measured using digital 
image analysis and subject self-assessment of change from baseline in hair growth as measured by the distribution of 
SSA scores 
 
 
 
 
 
 
 
  
 
  
 
 
General Statistical Methods and Types of Analyses  
Two analysis populations are defined: modified intent-to-treat (mITT) and safety. The mITT population, consisting 
of all randomized subjects who have a baseline and at least 1 postbaseline primary efficacy measurement, will be 
used for analyses of efficacy data based on the randomized treatment group. The safety population, consisting of all 
treated subjects, will be used for analyses of all safety data based on the actual treatment received. Hypothesis 
testing will be 2-tailed with a significance level of 0.05. Pairwise comparisons of setipiprant tablets 1000 mg BID 
versus placebo will be made. The finasteride subjects enrolled prior to protocol Amendment 1 will be summarized 
alone and will not be included in the analysis models to compare with the other treatment groups. For all efficacy 
analyses, no adjustment of significance levels will be made for multiplicity of treatment comparisons. 
Efficacy Analyses: The 2 coprimary efficacy variables are: 1) change from baseline in TAHC of terminal hairs/cm2 
within a 1 cm2 circular area on the left side at Week 24; and 2) SSA of change from baseline in hair growth at 
Week 24. The 2 coprimary efficacy variables will be analyzed using an analysis of covariance (ANCOVA) model 
with treatment (excluding the finasteride group as described above) as a fixed effect and age and baseline value as 
covariates (if applicable). The treatment difference for setipiprant tablets 1000 mg BID versus placebo BID will be 
constructed based on this ANCOVA model, along with the 2-sided p-value. 
 
 
 
 
 
 
 
 
. Missing data of TAHC and SSA will be imputed up to Week 24 using last observation carried forward 
(LOCF). 

 
 
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Safety Analyses: All safety analyses will be performed on the safety population. Adverse events will be coded from 
the verbatim text into preferred term (PT) and primary system organ class (SOC) by using the Medical Dictionary 
for Regulatory Activities. The number and percent of subjects reporting treatment-emergent AEs at least once 
regardless of causality will be tabulated. Similarly, treatment-related AEs will be tabulated. The tables will be 
generated by primary PT and SOC as well as by severity. Safety data will be summarized by frequency distributions 
or descriptive statistics and described in the detailed analysis plan. 
 
 
 
  
Sample Size Calculation: The study plans to enroll approximately 152 subjects in the setipiprant 1000 mg BID 
(n = 80) and placebo BID (n = 72) groups. Of the 152 subjects to be enrolled, 12 subjects will be randomized to the 
 The remaining 140 subjects will be randomized 
 at 1:1 ratio and stratified by baseline age group (18 to 34 and 35 to 49 years). 
 
 
 
 
 
 

 
 
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1. 
Background and Clinical Rationale  
Androgenetic alopecia (AGA) is the most prevalent cause of hair loss in both men and women 
(Sinclair, 1998; Severi et al, 2003; Stough et al, 2005). It has been estimated that across the 
lifespan of a person, AGA may affect approximately 70% of men and 40% of women 
(McElwee and Shapiro, 2012). For many among those affected by AGA, research suggests that 
negative psychological effects can occur as a result of the condition (Tabolli et al, 2013). As 
such, the field of dermatology has had a high interest in developing effective treatments for 
AGA. Currently available treatment options provide some clinical benefit in treating AGA. 
However, monotherapy with these agents provide either limited efficacy or have been associated 
with unfavorable side effect profiles (Falto-Aizpurua et al, 2014; DiLoreto et al, 2014; 
Altomare et al, 2002; Caruso et al, 2015). Finasteride is approved only for male patients. Thus, 
innovative treatment approaches are needed in the search for agents that provide improved 
efficacy and tolerability for treatment of subjects with AGA.  
Research suggests a role of the prostaglandin pathway in the inhibition of hair growth and is 
based on the following findings: a) the level of prostaglandin D2 (PGD2) in the balding scalp of 
men with AGA is significantly elevated when compared with the level in nonbalding scalp in the 
same individual; b) PGD2 blocks the growth of human hair follicle mini organ in ex vivo 
cultures; and c) topical application of PGD2 to the back of wild type mice prevents hair growth 
(Garza et al, 2012). The enzyme responsible for synthesizing the agonist to PGD2, 
prostaglandin-D2 synthase (PTGDS), is expressed in nonpermanent keratinocytes of the human 
hair follicle (Garza et al, 2012). Mice genetically engineered to overexpress the mouse PTGDS 
homolog (ptgs2) are unable to grow hair suggesting that increased PGD2 prevents hair growth 
(Garza et al, 2012). The G-protein-coupled receptor for PGD2 is a chemoattractant receptor-
homologous molecule expressed on T helper 2 cells (CRTH2). CRTH2 is expressed in the 
dermal papilla and outer root sheath cells of human hair follicles (Colombe et al, 2008). In 
CRTH2 knockout mice, hair growth is insensitive to topical PGD2 application, thereby 
suggesting that the growth inhibitory effect is mediated by the CRTH2 receptor (Garza et al, 
2012). The growth inhibitory effect of PGD2 can be abolished in human hair follicle mini organ 
culture with CRTH2 antagonists (Cotsarelis et al, 2015a). 
 
 
 
 
 
 

 
 
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Setipiprant effectively prevents PGD2-induced hair growth inhibition in human hair follicle mini 
organ cultures (Cotsarelis et al, 2015b). Thus, the purposes of this study include the use of the 

 
 
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study data to develop a better understanding of whether setipiprant tablets are capable of treating 
AGA in males and to assist in the design of future clinical trials.   
2. 
Study Objectives and Clinical Hypotheses  
2.1 
Study Objectives 
The study objectives are:  
1) To evaluate the safety, tolerability, and efficacy of oral administration of setipiprant 
tablets 1000 mg BID relative to placebo in males with AGA who are 18 to 49 years old and in 
generally good health. 
. 
2.2 
Clinical Hypotheses 
• Setipiprant tablets 1000 mg BID have an acceptable safety profile following oral 
administration for 24 weeks. 
• Setipiprant tablets 1000 mg BID are more effective than placebo in increasing hair growth, as 
measured by the change from baseline in target area hair count (TAHC) of terminal hairs 
(1 cm2 circular area) using digital image analysis at 24 weeks after oral administration. 
• Setipiprant tablets 1000 mg BID are more effective than placebo in increasing scalp hair 
growth, as measured by the distribution of Subject Self-Assessment (SSA) scores using a 
7-point scale at 24 weeks after oral administration. 
3. 
Study Design 
This is a multicenter, randomized, double-blind, placebo-controlled study with an active 
comparator group designed to determine the effect of treatment with setipiprant tablets 1000 mg 
BID on scalp hair growth as assessed by objective (ie, imaging-based) and subjective (ie, 
investigator- and subject-reported) measures.  
All investigators, site staff, and subjects will be blinded to whether subjects receive setipiprant or 
matching placebo during the study. 
Subjects must complete all screening and baseline procedures and meet all eligibility 
requirements to qualify for enrollment and randomization on Day 1 when they will be randomly 

 
 
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assigned to 1 of 2 treatment groups (setipiprant or placebo). All subjects will self-administer the 
assigned study drug over a 24 week period to evaluate the safety and effects on hair growth. 
After randomization, subjects will return to the research facility at Weeks 
,
 24 for 
protocol-defined efficacy and/or safety assessments and procedures, confirmation of compliance 
with study drug usage, and new study drug dispensation (except for Week 24). A follow-up visit 
will occur at Week 32 (ie, 8 weeks posttreatment) or the early exit visit for protocol-defined 
efficacy and safety evaluations and procedures.  
Safety and efficacy assessments and study procedures are outlined in the Study Design and 
Schedule of Assessments (Table 1). The SSA will be evaluated at Weeks 
 24, and 32 (or 
early exit visit) using the subject’s paired and randomly blinded screening (the screening 
photograph is defined as the subject’s baseline) and postbaseline photographs, and at Weeks 24 
and 32 (or early exit visit) using the subject’s paired, unblinded screening and postbaseline 
photographs. 
 
 
 
 
 
 
 
 
 
  
3.2 
Data Monitoring Committee 
Although a data monitoring committee will not be established for this study, the medical safety 
physician (MSP) will perform an ongoing review of safety data in a blinded manner throughout 
the 24-week treatment period.  
4. 
Study Population and Entry Criteria 
4.1 
Number of Subjects  
Approximately 152 subjects will be randomized to 1 of 2 treatment groups (setipiprant 1000 mg 
BID, n = 80; placebo BID, n = 72) at up to 20 study centers in the US.  

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 Approximately 140 subjects will be randomized in a 1:1 ratio to 
 
group (setipiprant 1000 mg BID, placebo BID), and stratified by baseline age, 18 to 34 and 35 to 
49 years.). 
 
4.2 
Study Population Characteristics 
Males, aged 18 to 49 years (inclusive) and in generally good health, with AGA vertex patterns 
IIIv, IV, or V on the Norwood-Hamilton Hair Loss Scale (NHS; Norwood, 1975; A12.1.2), will 
be included in this study. Males aged 18 to 41 years were also assigned to finasteride prior to 
protocol Amendment 1. 
4.3 
Inclusion Criteria 
The following are requirements for entry into the study:  
1. Written informed consent
2. Written documentation in accordance with the relevant country and local privacy
requirements, where applicable (eg, Written Authorization for Use and Release of Health and
Research Study Information)
3. Males, aged 18 to 49 years (inclusive) and in generally good health
4. Androgenetic alopecia with vertex patterns IIIv, IV, or V on the NHS
6. Agreement from the subject to maintain current hair care regimen 
 and refrain from hair weaving, hair
colorants or dyes, and nonstudy hair growth products for the duration of the study

 
 
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4.4 
Exclusion Criteria 
The following are criteria for exclusion from participating in the study: 
1. History or evidence of hair loss for reasons other than AGA 
 
 
2. Scarring of the scalp or any condition or disease of the scalp, hair, or hair shaft 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. Hair-weaving procedure within 6 months prior to baseline 
6. Use of hair colorants or dyes within 6 months prior to baseline or presence of residual traces 
of colorants in the hair at baseline   
7. Patients who have a clinically significant finding or condition (eg, patients with malignancies, 
HIV, or other immunocompromising conditions), any uncontrolled systemic disease, or are in 

 
 
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4.5 
Permissible and Prohibited Medications/Treatments 
4.5.1 
Permissible Medications/Treatments 
Therapy considered necessary for the subject's welfare may be given at the discretion of the 
investigator. If the permissibility of a specific medication/treatment is in question, please contact 
the sponsor. 
4.5.2 
Prohibited Medications/Treatments 
The decision to administer a prohibited medication/treatment is done with the safety of the 
subject as the primary consideration. When possible, the sponsor should be notified before the 
prohibited medication/treatment is administered. 
 
 
: 
 
 
 
 
 
 
 

 
 
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The investigator will record details of all concomitant medication use and concurrent procedures.  
4.5.3 
Special Activities 
Subjects must refrain from changing their hair style and hair color for the duration of the study. 
Excessive use of hair sprays or hair dryers should be avoided.  
5. 
Study Treatments  
5.1 
Study Treatments and Formulations 
From randomization 
, the study drug will be dispensed for oral dosing to 
subjects in tablet form as follows:  
Setipiprant: Two setipiprant tablets at 500 mg BID  
 
 
  

 
 
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5.2 
Control Treatments 
Placebo: Two placebo tablets BID 
 
 
 
5.3 
Methods for Masking/Blinding 
Evaluation of the setipiprant and placebo treatment groups will be conducted in a double-blind 
manner so that neither the site personnel nor the subject is aware of which treatment is 
administered. Both treatments will be identical in appearance 
Except when it is essential for the medical management of the subject or bioanalytical reasons 
(ie, to enable bioanalysis of samples only from subjects who receive active treatment), 
unblinding the treatment assignment will be considered a protocol deviation. Instructions for 
access to emergency treatment allocation information will be available by secured access to the 
interactive web response system (IWRS). If possible, the investigator should contact the sponsor 
before unblinding any subject’s treatment assignment. In the event that this is not possible, the 
sponsor must be notified within 24 hours after the unblinding event. After unblinding, the subject 
will be discontinued from study drug treatment and will return for a final follow-up (ie, Week 32 
or early exit visit).  
5.4 
Treatment Allocation Ratio and Stratification 
 
. The 140 subjects 
 will be randomized to 
setipiprant and placebo at a 1:1 ratio to be stratified by baseline age group (18 to 34 and 35 to 
49 years). 
5.5 
Method for Assignment to Treatment Groups/Randomization 
At screening, each subject who provides informed consent will be assigned a subject number that 
will serve as the subject identification number on all study documents. 
At the time of randomization (ie, Day 1 [baseline] visit), eligible subjects will be randomly 
assigned. 
 
 subjects will be 

 
 
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randomized in a 1:1 ratio to receive setipiprant tablets 1000 mg BID or placebo BID stratified by 
baseline age group (18 to 34 and 35 to 49 years).  
An automated IWRS will be used to manage the randomization and treatment assignment based 
on a randomization scheme prepared by Allergan Biostatistics. 
Study medication will be labeled with medication kit numbers. The IWRS system will provide 
the site with the specific medication kit number(s) for each randomized subject at the time of 
randomization. Sites will dispense study drugs according to the IWRS instructions. Sites will 
also log into the IWRS at subsequent visits to obtain a study drug kit number(s) for study drugs 
as required. Sites will receive the IWRS confirmation notifications for each transaction. All 
notifications are to be maintained with the study source documents. 
5.6 
Treatment Regimen and Dosing 
Each subject will self-administer their respective treatment for 24 weeks as follows: 
Setipiprant and placebo regimen: Subjects will self-administer the assigned study drug (2 tablets 
of setipiprant 500 mg or placebo) orally with water at approximately 12-hour intervals and at 
least 1 hour before or 2 hours after eating, eg, 1 hour before breakfast in the morning and at least 
2 hours after dinner. Subjects assigned to the finasteride group prior to protocol Amendment 1 
will continue treatment until they complete the study. 
5.7 
Storage of Study Drugs 
Study drugs must be stored in a secure area and dispensed only to subjects entered into the 
clinical study, at no cost to the subject, in accordance with the conditions specified in the 
protocol. 
Sites should store study drugs at controlled room temperature between 
 
. Sites will monitor the temperature of the storage area and report any temperature 
excursions as described in the study reference manual or contact the sponsor or its designee for 
further instructions. 
Subjects will be instructed on the proper storage of study drugs and to keep it out of the reach of 
children. All study drug packages will have child-resistant features. 
5.8 
Preparation of Study Drugs 
Not applicable 

 
 
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5.9 
Treatment Administration  
From randomization through Week 24, subjects will self-administer 2 setipiprant 500 mg tablets 
BID or 2 placebo tablets BID.  
Setipiprant and placebo packaging and dosing: Setipiprant and placebo will be packaged in 
blister packs containing the coated tablets and combined into a weekly wallet. Each weekly 
wallet of setipiprant or placebo will contain a total of 14 doses (ie, a week’s worth of BID 
dosing).  
 
 
 
 
  
The investigator will dispense an appropriate number of weekly wallets for the time interval until 
the subject’s next clinic visit. Because this is a double-blind study, labeling of the subject 
treatment kit will not show the treatment allocation. All other information required by regulation 
will appear on each treatment kit.  
6. 
Response Measures and Summary of Data Collection Methods 
6.1 
Efficacy Measures   
Multiple products have been studied and approved for the treatment of AGA in recent years and 
have employed objective hair counts, cumulative width, and darkness estimates via 
macrophotography; independent investigator, subject, and expert panel comparative evaluations 
of pre- and posttreatment global photographs; and multi-item subject questionnaires. Similar 
procedures, assessments, and questionnaires will be utilized in this study. 
To avoid introducing response bias during the study, the subject must complete the self-
assessments independently and prior to evaluation by the investigator (ie, the subject-reported 
assessments must be completed before the investigator-reported assessments). The investigator’s 
current or previous evaluations must not be disclosed to the subject nor must the subject be 
reminded of any of his previous responses provided during any assessment. For unbiased 
investigator assessments, subject responses must also not be disclosed to the evaluating 
investigator.  

 
 
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All staff and subjects will be blinded to whether subjects receive setipiprant or matching placebo 
during the study. Staff must administer all subject assessments and not divulge the results of 
these assessments to the evaluating investigator. The sponsor will provide guidance regarding 
what study personnel may say and must not say to a subject regarding any perceived 
improvement to avoid influencing responses on the subject-reported assessments. When possible, 
the evaluator(s) performing the 
 at an individual study 
center should perform all evaluations for a given subject, and if possible, all subjects throughout 
the study. In the rare event that there is a change in the assigned evaluator for a given subject, the 
reason for change must be documented. If it is not possible to use the same evaluator to follow a 
given subject, the sponsor recommends that evaluations between the primary and subsequent 
evaluator overlap (ie, both evaluators should examine the subject together and discuss findings 
without the subject present) for at least 1 visit; this should be documented. 
6.1.1 
Primary Efficacy Measures 
6.1.1.1 
Target Area Hair Count (Within a 1 cm2 Circular Area) 
One of the coprimary efficacy measures will be the subjects’ TAHC as measured in terminal 
hairs (1 cm2 circular area on the left side) using digital image analysis (A12.1.4). 
 
 
 
 
 
  
The total number of terminal hairs (hair width ≥ 30 µm) will be calculated from 
macrophotographs. The target area used to count TAHC will be a 1 cm2 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 semipermanent microdot tattoo to ensure the same target area is 
reproduced at each visit. 
6.1.1.2 
Subject Self-Assessment 
The SSA (A12.1.7) is a coprimary measure that consists of a single item that assesses each 
subject’s perception of change in scalp hair growth. The subject uses a standardized global 
photograph of his scalp taken at the screening visit (the screening photograph is defined as the 
subject’s baseline) presented side by side with a standardized global photograph taken at the 
postbaseline visit to give a comparative score. The photographs are presented in a blinded and 
randomized manner, and response options are on a 7-point ordinal scale. Refer to the imaging 
vendor manual for the methodology for obtaining global photographs.  

 
 
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6.3 
Safety Measures 
Safety measures will include AEs, vital sign measurements (pulse rate, blood pressure, and 
respiratory rate), physical examinations, 12-lead ECG, and laboratory tests (biochemistry, 
hematology, and urinalysis).  
6.3.1 
Adverse Events 
The investigator will question the subject to ascertain whether any AEs were experienced since 
the previous visit. All pertinent information regarding AEs (ie, date of onset and stop, duration, 
outcome, severity, relationship to study drug, action or required treatment) will be obtained and 
recorded in the source documents and appropriately transcribed on the electronic case report 
form (eCRF) page. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 

 
 
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6.3.6 
Nonscalp Hair Growth 
Starting at Week 8, subjects will be queried at each visit whether they have noticed any hair 
growth in nonscalp areas (yes/no) and this response will be captured in the eCRF. If judged by 
the investigator as clinically significant, nonscalp hair growth may be reported as an AE.  

 
 
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6.4 
Examination Procedures, Tests, Equipment, and Techniques 
All study photographs will be standardized for lighting, camera angle, and position of the 
subject’s head 
 Images will be uploaded to a secure website 
made available by the photography vendor, 
 via flash drive or internet 
transfer. Detailed instructions for all aspects of the photography procedures will be supplied 
separately 
. 
6.4.1 
Semipermanent Microdot Tattoo 
For standardized photography, during the Day 1 (baseline) visit, subjects will receive two 1-mm 
semipermanent microdot tattoos 
 
 
 
 
 
 
. As the dots begins to fade or are at risk of fading before the next scheduled 
visit, they may be refreshed in the exact same locations.  
6.4.2 
Global Photographs  
Two standardized global photographs (vertex target area and frontal area) will be taken at 
screening (the screening photograph is defined as the subject’s baseline) and at Weeks 
, 24, 
and 32 (or early exit visit). At Weeks 
, 24, and 32 (or early exit visit), after refreshing the 
semipermanent microdot tattoo (if necessary) and parting and combing the hair radially away 
from the part, standardized global photographs of the subject’s vertex target area will be 
presented in pairs (ie, 1 photograph taken at screening and the other photograph taken at a given 
treatment week 
 
  

 
 
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6.4.3 
Macrophotography 
Macrophotography will be performed at Day 1 (baseline) and Weeks 
, 24, and 32 (or early 
exit visit). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
6.5 
Summary of Methods of Data Collection 
This study will use eCRFs using remote electronic data capture through a qualified third party 
vendor. The data will be entered on the eCRFs in a timely manner on an ongoing basis. The 
investigator is responsible for ensuring that data are properly recorded on each subject’s eCRFs 
and related documents. An investigator who has signed the protocol signature page should 
personally electronically sign for the eCRFs (as indicated in the eCRFs) to ensure that the 
observations and findings are recorded on the eCRFs correctly and completely. A certified 
electronic copy of the eCRFs including data corrections will be provided to the site for archiving 
at the end of the study. 
 
 
 
 
 
 
 
 
 
 

 
 
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. 
 
 
 
 
 
  
 
  
6.6 
Other Study Supplies 
The following will be provided by the sponsor: 
• Modified NHS 
The following will be provided by the investigator: 
 
 
 
 
  
 
 
 
 
• Sterile pads 
• Gloves 
• Sphygmomanometer 
• Equipment to measure height and body weight 
• Equipment (stethoscope, otoscope, etc) to conduct physical examinations 
• Internet connection (high-speed connection for eCRF completion and digital image uploads) 
The following will be provided by the central laboratory: 
• All supplies needed for 
 
• Shipping materials for shipment 
 

 
 
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The following will be supplied by 
.: 
• Standardized photography equipment, including the instruction manual 
• Equipment for tattoo and shaving 
 
•
 
7. 
Statistical Procedures 
7.1 
Analysis Populations 
Two analysis populations are defined: modified intent-to-treat (mITT) and safety. The mITT 
population, consisting of all randomized subjects who have a baseline and at least 1 postbaseline 
measurement for 1 of the coprimary efficacy measures, will be used for analyses of efficacy data 
based on the randomized treatment group. The safety population, consisting of all subjects who 
receive at least 1 dose of study drug (ie, all treated subjects), will be used for analyses of all 
safety data based on the actual treatment received. All subjects who ingest at least 1 dose of 
study drug will be included in the safety analysis population included in the summaries of all 
safety and demographic data. All efficacy variables will be summarized and analyzed using the 
mITT population. 
7.2 
Collection and Derivation of Primary and Other Efficacy 
Assessments 
The coprimary efficacy variables will be based on the following 2 measures: TAHC within a 
1 cm2 circular area on the left side of the scalp and SSA. 
• The TAHC is a standardized objective quantification of each subject’s number of terminal 
hairs (hair width ≥ 30 µm) within a 1 cm2 target circular area on the left side located at the 
anterior leading edge of the vertex thinning area of the scalp using digital image analysis. 
• The SSA score is the subject’s assessment of change of hair growth, scored on a 7-point scale 
(−3 = greatly decreased, −2 = moderately decreased, −1 = slightly decreased, 0 = remained the 
same, +1 = slightly increased, +2 = moderately increased, and +3 = greatly increased). The 
analyses of the SSA from the blinded photograph assessments will be based on the actual 
change from the screening photographs (ie, if the postbaseline photograph is used as Photo A, 
the assessment score will be reversed for analyses).  

 
 
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7.2.1 
Primary Efficacy Variables  
The 2 coprimary efficacy variables are based on the measurements of TAHC and SSA (blinded).  
• Change from baseline in TAHC within a 1 cm2 target circular area on the left side located at 
the anterior leading edge of the vertex thinning area of the scalp at Week 24 
• Subject Self-Assessment of change from baseline in hair growth as viewed on the subject’s 
paired (before and after presented in a blinded fashion) global photographs of the vertex 
target area at Week 24 and measured by the distribution of SSA scores  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

 
 
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• Independent Global Panel Review o
 
 
 
 
 
 
  
 
 
7.3 
Hypothesis and Methods of Analysis 
Finasteride subjects enrolled prior to protocol Amendment 1 will be summarized alone and will 
not be included in the analysis models. Hypothesis testing will be 2-tailed with a significance 
level of 0.05. Comparisons of setipiprant tablets 1000 mg BID versus placebo BID will be made. 
For all efficacy analyses, no adjustment of significance levels will be made for multiplicity of 
treatment comparisons. 
7.3.1 
Primary Efficacy Analyses 
For analyses of TAHC, the following set of hypotheses will be used to compare setipiprant 
tablets 1000 mg BID versus placebo BID: 
• Null hypothesis: There is no difference between setipiprant tablets 1000 mg BID and placebo 
BID in increasing TAHC (terminal hairs in a 1 cm2circular area) as measured by the change 
from baseline at Week 24 using digital image analysis. 
• Alternative hypothesis: There is a difference between setipiprant tablets 1000 mg BID and 
placebo BID in increasing TAHC (terminal hairs in a 1 cm2 circular area) as measured by the 
change from baseline at Week 24 using digital image analysis. 
For analyses of the SSA, the following set of hypotheses will be used to compare setipiprant 
tablets 1000 mg BID versus placebo BID: 
• Null hypothesis: There is no difference between setipiprant tablets 1000 mg BID and placebo 
BID in SSA (blinded) of hair growth from baseline at Week 24. 
• Alternative hypothesis: There is a difference between setipiprant tablets 1000 mg BID and 
placebo BID in SSA (blinded) of hair growth from baseline at Week 24. 

 
 
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Change from baseline in TAHC at Week 24 and SSA of the change of hair growth from baseline 
at Week 24 will be analyzed using an analysis of covariance (ANCOVA) model with treatment as 
a fixed effect and age and baseline value as covariates (if applicable). The treatment difference 
(setipiprant tablets 1000 mg BID versus placebo BID) will be constructed based on this 
ANCOVA model, along with the 2-sided p-value. Finasteride subjects enrolled prior to protocol 
Amendment 1 will be summarized alone and will not be included in the analysis models. 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
  

 
 
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7.3.3 
Safety Analyses 
Adverse events will be coded from the verbatim text into preferred term (PT) and primary 
system organ class (SOC) by using the Medical Dictionary for Regulatory Activities. The 
number and percent of subjects reporting treatment-emergent AEs at least once regardless of 
causality will be tabulated. Similarly, treatment-related AEs will be tabulated. The tables will be 
generated by primary SOC and PT as well as by severity. 
Safety data will be summarized by frequency distributions or descriptive statistics and described 
in the detailed analysis plan. 
 
 
 
 
 
 
7.4 
Other Analyses 
Subject disposition, demographic data, and variables relating to the conduct of the study (eg, 
number of subjects attending each visit) will be summarized overall and by treatment. All data 
will be listed. The number of subjects enrolled will be summarized, overall and by treatment 

 
 
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7.5 
Sample Size Calculation 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.6 
Interim Analyses 
No interim analyses are planned.  
8. 
Study Visit Schedule and Procedures 
Please see Figure 1 for a flow diagram of study design. Table 1 provides the schedule of visits 
and procedures. 

 
 
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8.1 
Subject Entry Procedures 
8.1.1 
Overview of Entry Procedures 
Prospective subjects as defined by the criteria in Section 4.3 and Section 4.4 (inclusion/exclusion 
criteria) will be considered for entry into this study. 
8.1.2 
Informed Consent and Subject Privacy  
The study will be discussed with the subject, and a subject wishing to participate must give 
informed consent prior to any study-related procedures or change in treatment. The subject must 
also give authorization and other written documentation in accordance with the relevant country 
and local privacy requirements (where applicable) prior to any study-related procedures or 
change in treatment. 
Each subject who provides informed consent will be assigned a subject number via the IWRS 
that will be used on subject documentation throughout the study. 
 
 
 
  
 
 
 
 
  
 
 
8.3 
Procedures for Final Study Entry 
A subject is considered to have entered the study once the informed consent form is signed at the 
time of screening.  

 
 
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8.4 
Instructions for the Subjects 
Subjects will be instructed to self-administer the setipiprant tablets 1000 mg BID or placebo BID 
orally with water at least 1 hour before or 2 hours after eating, eg, 1 hour before breakfast in the 
morning and at least 2 hours after dinner. 
 
 
In addition, subjects will be required to follow further instructions outlined in Section 4.5.3 and 
in the procedure manual.  
8.5 
Unscheduled Visits 
If a subject is seen for an unscheduled visit, an assessment and record of AEs should be 
completed. Additional examinations may be performed as necessary to ensure the safety and 
well-being of patients during the study. The eCRFs should be completed for each unscheduled 
visit. 
8.6 
Compliance With Protocol 
At Weeks 
 24 clinic visits, site personnel will reconcile subject drug usage reports 
with inspection of wallets (setipiprant or placebo) returned by the subject (ie, numbers of open 
blisters, unused tablets in any blister, and unopened blisters) in the subject’s weekly supplies to 
document the level of subject compliance with the dosing schedule. 
 
Study drug 
inventory and accountability records must be kept current and available for review by the clinical 
site monitor. All used and unused
 for setipiprant or placebo should remain with their 
weekly wallet for reconciliation with reported usage (see above). Authorized study personnel, 
with the monitor’s guidance, are responsible to reconcile any discrepancies. 
If the subject is noncompliant with the dosing schedule (eg, frequent or lengthy periods of 
missed doses, overdosing), additional treatment kits will not be dispensed (ie, the subject may be 
discontinued from study drug treatment at the investigator's discretion after consultation with the 
sponsor). 

 
 
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8.7 
Early Discontinuation of Subjects 
Subjects may voluntarily withdraw from the study at any time. Notification of early subject 
discontinuation from the study and the reason for discontinuation will be made to the sponsor 
and will be clearly documented on the appropriate case report form. 
8.8 
Withdrawal Criteria 
A subject should be withdrawn from the study if the subject wishes to discontinue, or 
experiences an AE or has an abnormal laboratory result where, in the judgment of the 
investigator, continuation in the study would be detrimental to the subject’s health. Whenever 
possible, the decision to withdraw a subject from the study or study treatment should be 
discussed with the sponsor prior to discontinuation of the subject.  
8.9 
Study Termination 
The study may be stopped at his/her study site at any time by the site investigator. The sponsor 
may stop the study (and/or the study site) for any reason with appropriate notification. 
9. 
Adverse Events 
Adverse events occurring during the study will be recorded on an AE case report form. If AEs 
occur, the first concern will be the safety of the study participants. 
9.1 
Definitions 
9.1.1 
Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. In addition, during the screening period, AEs will be assessed regardless of the 
administration of a pharmaceutical product. 
Note: Adverse events must be collected once informed consent has been obtained, regardless of 
whether or not the subject has been administered study drug. 

 
 
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Progression of treatment indication including new or worsening of anticipated clinical signs or 
symptoms, which are collected as clinical efficacy variables and assessed as unequivocally 
associated with the disease progression and/or lack of efficacy, should NOT be reported as AEs 
unless the disease progression is greater than anticipated in the natural course of the disease. 
Adverse events will be assessed, documented, and recorded in the CRF throughout the study (ie, 
after informed consent has been obtained).
 
 
 
. All reported AEs will be documented on the appropriate case report form. 
9.1.2 
Serious Adverse Event 
A serious AE is any AE occurring at any dose that results in any of the following outcomes: 
death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, 
a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered a serious AE when, based upon appropriate medical judgment, they may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent 1 of the 
outcomes listed in this definition. (See Section 9.3 for procedures for reporting a serious AE.) 
The sponsor considers all cancer AEs as serious AEs.  
Preplanned surgeries or procedures for pre-existing, known medical conditions for which a 
subject requires hospitalization is not reportable as a serious AE. 
Any preplanned surgery or procedure should be clearly documented in the site source documents 
by the medically qualified investigator at the time of the subject’s entry into the study. If it has 
not been documented at the time of the subject’s entry into the study, then it should be 
documented as a serious AE and reported to the sponsor. 

 
 
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9.1.3 
Severity 
A clinical determination will be made of the intensity of an AE. The severity assessment for a 
clinical AE must be completed using the following definitions as guidelines: 
Mild 
Awareness of sign or symptom, but easily tolerated 
Moderate 
Discomfort enough to cause interference with usual activity 
Severe 
Incapacitating with inability to work or do usual activity 
Not applicable 
In some cases, an AE may be an all or nothing finding which cannot be 
graded. 
9.1.4 
Relationship to Study Drug or Study Procedure 
A determination will be made of the relationship (if any) between an AE and the study drug or 
study procedure, as applicable. A causal relationship is present if a determination is made that 
there is a reasonable possibility that the AE may have been caused by the drug or study 
procedure. 
9.2 
Procedures for Reporting Adverse Events 
Any AE must be recorded on the appropriate case report form. 
All AEs that are drug-related and unexpected (not listed as treatment-related in the current 
investigator's brochure) must be reported to the governing institutional review board/independent 
ethics committee (IRB/IEC) as required by the IRB/IEC, local regulations, and the governing 
health authorities. An AE that is marked ongoing at the exit visit may need to be followed up as 
appropriate.  
 
 
 
 
 
 
 
 
 

 
 
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In the event of a serious AE, the investigator must: 
1. Notify the sponsor immediately by fax or email using the serious AE form (contact details can 
be found on page 1 of the serious AE form); phone numbers and relevant sponsor’s personnel 
contacts are also on the front page of protocol and study contacts page. 
2. Obtain and maintain in his/her files all pertinent medical records, information, and medical 
judgments from colleagues who assisted in the treatment and follow-up of the subject. 
3. Provide the sponsor with a complete, written description of the AE(s) on the serious AE form 
describing the event chronologically, including any treatment given (eg, medications 
administered, procedures performed) for the AE(s). Summarize relevant clinical information 
about the event: signs, symptoms, diagnosis, clinical course and relevant clinical laboratory 
tests, etc. Include any additional or alternative explanation(s) for the causality which includes 
a statement as to whether the event was or was not related to the use of the investigational 
drug. 
4. Promptly inform the governing IRB/IEC of the serious AE as required by the IRB/IEC, local 
regulations, and the governing health authorities. 
 
 
 
 
 
 
 
 
 
The treatment assignment for the subject can be determined by designated site personnel logging 
into the IWRS system via password protected access. The reason for breaking the code must be 
recorded in the subject’s source documents. 
10. 
Administrative Items 
This protocol is to be conducted in accordance with the applicable GCP regulations and 
guidelines, eg, the ICH Guideline on GCP. 

 
 
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10.1 
Protection of Human Subjects 
10.1.1 
Compliance with Informed Consent Regulations (US 21 CFR 
Part 50) and Relevant Country Regulations 
Written informed consent is to be obtained from each subject prior to any study-related activities 
or procedures in the study, and/or from the subject's legally authorized representative.  
10.1.2 
Compliance With IRB or IEC Regulations 
This study is to be conducted in accordance with IRB regulations (US 21 CFR Part 56.103) or 
applicable IEC regulations. The investigator must obtain approval from a properly constituted 
IRB/IEC prior to initiating the study and re-approval or review at least annually. The sponsor is 
to be notified immediately if the responsible IRB/IEC has been disqualified or if proceedings 
leading to disqualification have begun. Copies of all IRB/IEC correspondence with the 
investigator should be provided to the sponsor. 
10.1.3 
Compliance With Good Clinical Practice 
This protocol is to be conducted in accordance with the applicable GCP regulations and 
guidelines. 
10.1.4 
Compliance With Electronic Records; Electronic Signatures 
Regulations (US 21CFR Part 11) 
This study is to be conducted in compliance with the regulations on electronic records and 
electronic signature. 
10.2 
Changes to the Protocol 
The investigator must not implement any deviation from or changes of the protocol without 
approval by the sponsor and prior review and documented approval/favorable opinion from the 
IRB/IEC of a protocol amendment, except where necessary to eliminate immediate hazards to 
study subjects, or when the changes involve only logistical or administrative aspects of the study 
(eg, change in monitors, change of telephone numbers). 
10.3 
Subject Confidentiality 
A report of the results of this study may be published or sent to the appropriate health authorities 
in any country in which the study drug may ultimately be marketed, but the subject’s name will 

 
 
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not be disclosed in these documents. The subject's name may be disclosed to the sponsor of the 
study, Allergan, or the governing health authorities or the FDA if they inspect the study records. 
Appropriate precautions will be taken to maintain confidentiality of medical records and personal 
information. 
10.3.1 
Subject Privacy 
Written authorization and other documentation in accordance with the relevant country and local 
privacy requirements (where applicable) is to be obtained from each subject prior to enrollment 
into the study, and/or from the subject's legally authorized representative in accordance with the 
applicable privacy requirements (eg, HIPAA). 
In accordance with HIPAA requirements, additional purposes of this study may include 
publishing of anonymous patient data from the study. 
10.4 
Documentation 
10.4.1 
Source Documents 
Source documents may include a subject's medical records, hospital charts, clinic charts, secure 
digital cards, photographs, patient-reported outcomes, the investigator's subject study files, as 
well as the results of diagnostic tests 
. The 
investigator's copy of the case report forms serves as part of the investigator's record of a 
subject's study-related data.  
The following information should be entered into the subject's medical record: 
• Subject’s name 
• Subject’s contact information 
• Date that the subject entered the study, subject number, and subject randomization (or 
medication kit[s]) number 
• Study title and/or protocol number of the study and the name of the sponsor 
• A statement that informed consent was obtained (including the date) and a statement that 
written authorization or other country and local subject privacy required documentation for 
this study has been obtained (including the date) 

 
 
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• Dates of all subject visits 
• Medical history, including HIV status 
• Eligibility criteria 
• Count of returned study medication 
• Record of all hair products used by the subject 
• Date the subject exited the study and a notation as to whether the subject completed the study 
or reason for discontinuation 
• Date of global and macrophotography (and approval of global photography at screening) 
• All subject and investigator assessments 
• Physical examination 
• Vital sign measurements 
• All concomitant medications (List all prescription and nonprescription medications being 
taken at the time of enrollment. At each subsequent visit, changes to the list of medications 
should be recorded.) 
• Occurrence and status of any AEs 
 
 
 
 
• Modified Norwood-Hamilton classification 
• Global photographs 
• Macrophotographs 
10.4.2 
Case Report Form Completion 
The investigator is responsible for ensuring that data are properly recorded on each subject's case 
report forms and related documents. An investigator who has signed the protocol signature page 

 
 
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should personally sign for the case report forms (as indicated in the case report forms) to ensure 
that the observations and findings are recorded on the case report forms correctly and 
completely. The case report forms are to be submitted to the sponsor in a timely manner at the 
completion of the study, or as otherwise specified by the sponsor and will be maintained in a 
central data repository. 
10.4.3 
Study Summary 
An investigator's summary will be provided to the sponsor within a short time after the 
completion of the study, or as designated by the sponsor. A summary is also to be provided to the 
responsible IRB/IEC. 
10.4.4 
Retention of Documentation 
All study-related correspondence, subject records, consent forms, subject privacy documentation, 
records of the distribution and use of all investigational products, and copies of case report forms 
should be maintained on file. 
For countries falling within the scope of the ICH guidelines, the sponsor-specific essential 
documents should be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the investigational product. These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirement(s) or if needed by 
the sponsor. 
The sponsor requires that it be notified in writing if the investigator wishes to relinquish 
ownership of the data so that mutually agreed upon arrangements can be made for transfer of 
ownership to a suitably qualified, responsible person. 
10.5 
Labeling, Packaging, and Return or Disposal of Study 
drugs/Treatments 
10.5.1 
Labeling/Packaging 
Setipiprant and placebo will be packaged 
 and 
combined into a weekly wallet. Each weekly wallet of setipiprant or placebo will contain a total 
of 14 doses (ie, a week’s worth of BID dosing). The investigator will dispense an appropriate 
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As this is a double-blind study, labeling of the subject treatment kit will not show the treatment 
allocation. All other information required by regulation will appear on each treatment kit. 
10.5.2 
Clinical Supply Inventory 
The investigator must keep an accurate accounting of the number of investigational units 
received from the sponsor, dispensed to the subjects, the number of units returned to the 
investigator by the subject (if applicable), and the number of units returned to the sponsor during 
and at the completion of the study. A detailed inventory must be completed for the study drug. 
The study drug must be dispensed only by appropriately qualified site personnel to subjects in 
the study. The medication is to be used in accordance with the protocol for subjects who are 
under the direct supervision of an investigator. 
10.5.3 
Return or Disposal of Study Drugs and/or Supplies 
All clinical study drugs/treatments and/or supplies will be returned to the sponsor or sponsor 
designee for destruction. 
10.6 
Monitoring by the Sponsor 
A representative of the sponsor will monitor the study on a periodic basis. The determination of 
the extent and nature of monitoring will be based on considerations such as the objective, 
purpose, design, complexity, blinding, size, and endpoints of the study. 
Authorized representatives of the sponsor or regulatory authority representatives will conduct 
onsite visits to review, audit and copy study-related documents. These representatives will meet 
with the investigator(s) and appropriate staff at mutually convenient times to discuss study-
related data and questions. 
 
 
 
 
 
  
 
 
 

 
 
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. All samples will be returned to the 
sponsor or sponsor designee at the completion of the study. The sponsor shall have full 
ownership rights to any biological specimens/samples derived from the study.  
Details about the handling of 
 are provided in the study laboratory 
manual.  
10.8 
Publications 
The sponsor as the sponsor has proprietary interest in this study. Authorship and manuscript 
composition will reflect joint cooperation between multiple investigators and sites and the 
sponsor personnel. Authorship will be established prior to the writing of the manuscript. As this 
study involves multiple centers, no individual publications will be allowed prior to completion of 
the final report of the multicenter study except as agreed with the sponsor. 
10.9 
Coordinating Investigator 
A signatory coordinating investigator will be designated prior to the writing of the clinical study 
report. 

 
 
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11. 
References 
Altomare G, Capella GL. Depression circumstantially related to the administration of finasteride 
for androgenetic alopecia. J Dermatol. 2002;29(10):665-669. 
Canfield D. Photographic documentation of hair growth in androgenetic alopecia. Dermatol Clin. 
1996;14(4):713-721. 
Canfield D. Photographic documentation of hair growth in androgenetic alopecia. Dermatol Clin. 
1999;17(2):261-269. 
Caruso D, Abbiati F, Giatti S, et al. Patients treated for male pattern hair with finasteride show, 
after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and 
plasma. J Steriod Biochem Mol Biol. 2015;146:74-79. 
Colombe L, Michelet JF, Bernard, BA. Prostanoid receptors in anagen human hair follicles. Exp 
Dermatol. 2008;17(1):63-72. 
Cotsarelis G, Zheng Y, Hsieh J. Evaluation of DP-2 antagonists in promotion of hair growth. 
Philadelphia: University of Pennsylvania; 2015a. 
Cotsarelis G, Zheng Y, Hsieh J. Demonstration that setipiprant effectively prevents PGD 
induced hair growth inhibition in human hair follicle mini organ cultures. Philadelphia: 
University of Pennsylvania; 2015b. 
DiLoreto C, LaMarra F, Mazzon G, Belgrano E, Trombetta C, Cauci S. Immunohistochemical 
Evaluation of Androgen Receptor and Nerve Structure Density in Human Prepuce from Patients 
with Persistent Sexual Side Effects after finasteride Use for Androgenetic Alopecia. PLOS One. 
2014;9(6):e100237. 
Falto-Aizpurua L, Choudhary S, Tosti A. Emerging treatments in alopecia. Expert Opin Emerg 
Drugs. 2014;19(4):545-556. 
Garza LA, Liu Y, Yang Z, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald 
scalp of men with androgenetic alopecia. Science Transl Med. 2012;4(126):126ra34-126ra34.  
Harcha G, Martinez B, Tsai TF, et al. A randomized, active- and placebo-controlled study of the 
efficacy and safety of different doses of dutasteride versus placebo and finasteride in the 
treatment of male subjects with androgenetic alopecia. J Am Acad Dermatol. 2014;70(3):489-
498.  

 
 
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McElwee KJ, Shapiro JS. Promising therapies for treating and/or preventing androgenic 
alopecia. Skin Therapy Lett. 2012;17(6):1-4. 
Norwood OT. Male pattern baldness: classification and incidence. South Med J. 1975;68:1359-
1365. 
Olsen EA, Hordinsky M, Whiting D, et al. The importance of dual 5alpha-reductase inhibition in 
the treatment of male pattern hair loss: results of a randomized placebo-controlled study of 
dutasteride versus finasteride. J Am Acad Dermatol. 2006;55(6):1014-1023.  
Savin RC. Evaluating androgenetic alopecia in male and female patients: an improved visual 
method of classifying and tracking hair loss using computer-generated male and female pattern 
and density scales. Kalamazoo, MI: The Upjohn Company; 1993.  
Severi G, Sinclair R, Hopper JL, et al. Androgenetic alopecia in men aged 40–69 years: 
prevalence and risk factors. Br J Dermatol. 2003;149(6):1207-1213. 
Sinclair R. Fortnightly review: male pattern androgenetic alopecia. Br Med J. 
1998;317(7162):865-869. 
Stough D, Stenn K, Haber R, et al. Psychological effect, pathophysiology, and management of 
androgenetic alopecia in men. Mayo Clinic Proceedings Proc. 2005;80(10):1316-1322. 
Tabolli S, Sampogna F, di Pietro C, Mannooranparampil TJ, Ribuffo M, Abeni D. Health status, 
coping strategies, and alexithymia in subjects with androgenetic alopecia: a questionnaire study. 
Am J Clin Dermatol. 2013;14(2):139-145. 

 
 
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12. 
Attachments  
12.1 
Examination Procedures, Tests, Equipment, and Techniques 

 
 
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12.2 
Safety Measures 
• Adverse events 
The investigator will question the subject in order to ascertain whether any AEs were 
experienced since the previous visit. All pertinent information regarding AEs (ie, date of onset 
and stop, duration, outcome, severity, relationship to study drug, action or treatment required) 
will be obtained and recorded in the source documents and appropriately transcribed on the 
eCRF page. 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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12.3 
Glossary of Abbreviations 
Term/Abbreviation 
Definition 
5AR 
5α-reductase 
AE 
adverse event 
AGA 
androgenetic alopecia 
 
 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
ASA 
Alopecia Symptom Assessment 
AST 
aspartate aminotransferase 
 
 
 
 
 
 
 
AUC0-inf 
area under the concentration-time curve from time 0 to infinity 
BID 
twice daily 
bpm 
beats per minute 
 
 
CMH 
Cochran-Mantel-Haenszel 
CRTH2 
chemoattractant receptor-homologous molecule expressed on T helper 
2 cells 
 
 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
 
 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
 
 
 
 
 
 
 
IRB 
Institutional Review Board 
IWRS 
interactive web response system 
LOCF 
last observation carried forward 

 
 
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MSP 
medical safety physician 
mITT 
modified intent-to-treat 
NHS 
Norwood-Hamilton Hair Loss Scale 
PGD2 
prostaglandin D2 
 
 
PT 
preferred term 
PTGDS 
prostaglandin-D2 synthase 
ptgs2 
mouse prostaglandin-D2 synthase homolog 
 
 
 
 
 
 
 
 
 
 
SOC 
system organ class 
SSA 
Subject Self-Assessment 
 
  
TAHC 
target area hair count 
 
 
 
 
TBL 
total bilirubin 
 
 
ULN 
upper limits of normal 
WBC 
white blood cell 
 

 
 
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12.4 
Protocol Amendment Summary 
Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study of 
Setipiprant Tablets in Androgenetic Alopecia in Males With a Comparator Arm 
Protocol 1922-201-002 Amendment 1 
Date of Amendment: February, 2017 
Amendment Summary 
This summary includes changes made to the original Protocol 1922-201-002 (25 March 2016). 
This protocol was amended to remove the finasteride arm, expand the upper range of the study 
population to age 49 years, and to remove some of the exclusionary concomitant medications. It 
is anticipated that these changes that are designed to simplify the protocol will result in an 
increased rate of study enrollment. 
Following is a summary of content-oriented changes that were made to each section of the 
protocol, and a brief rationale for these changes. Minor editorial and document formatting 
revisions have not been summarized. 

 
 
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Section 
Revision 
Rationale 
Protocol Title Page 
Deleted “With a Comparator Arm” 
from study title. 
Finasteride arm deleted. Data from 
the small number of finasteride 
subjects enrolled prior to protocol 
Amendment 1 will not be 
compared to other treatment 
groups. 
Protocol Title Page 
Revised fax number for Allergan 
Medical Safety Physician 
Previous fax number was incorrect. 
Protocol Summary, 
Study Objectives 
Revised overall age range of 
subjects in the setipiprant and 
placebo groups from 18 - 41 to 18 - 
49 years.  
Deleted finasteride arm. 
To increase the rate of study 
enrollment. 
Removed finasteride arm to 
simplify study design, allowing the 
age range to be expanded to up to 
49 years. The finasteride arm was 
deemed not critical in determining 
the efficacy or safety of setipiprant. 
Protocol Summary, 
Study Design, Structure 
Deleted finasteride arm. 
To be consistent with the removal 
of the finasteride arm. 
Protocol Summary, 
Study Design, Control 
Deleted finasteride arm. 
See rationale above. 
Protocol Summary, 
Study Design, 
Dosage/Dose Regimen 
Deleted finasteride arm 
See rationale above. 
Protocol Summary, 
Study Design, 
Enrollment/Stratification 
Deleted finasteride arm. Changed 
the randomization ratio for 
 
 
(setipiprant:placebo:finasteride) to 
1:1 (setipiprant:placebo). Changed 
the age range for stratification from 
35 – 41 years to 35 - 49 years.  
See rationale above. 
To be consistent with the revised 
study population. 
Protocol Summary, 
Study Population 
Characteristics, Key 
Inclusion Criteria  
Expanded the age range from 18 – 
41 years to 18 - 49 years.  
To be consistent with the revised 
study population. 
Protocol Summary, 
General Statistical 
Methods and Types of 
Analyses 
Deleted pairwise comparison of 
finasteride and placebo. 
Added finasteride subjects will be 
summarized alone. 
Finasteride arm was removed.  
To address how data from subjects 
treated with finasteride prior to 
protocol Amendment 1 will be 
analyzed. 
Protocol Summary, 
General Statistical 
Methods and Types of 
Analyses, Efficacy 
Analyses 
Added the finasteride group is 
excluded from analysis. 
Changed the age stratification in 
efficacy analysis model from 18 - 
34 and 35 - 41 years to < 35 and 
≥ 35 years. 
For clarification. 
To include those in the 42 - 
49 years age group (ie, ≥ 35 years) 

 
 
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Section 
Revision 
Rationale 
Protocol Summary, 
General Statistical 
Methods and types of 
Analyses, Sample Size 
Calculation 
Deleted finasteride arm (n = 35). 
Reduced enrollment target for 
setipiprant and placebo from 187 to 
152 subjects and 
enrollment 
target from 175 to 140 subjects.  
Randomization ratio for 
 
subjects changed from 2:2:1 
(setipiprant:placebo:finasteride) to 
1:1 (setipiprant:placebo). 
Finasteride arm removed. 
 
 
 
 
 
 
. 
1 Background and 
Clinical Rationale 
Deleted the finasteride arm. 
To be consistent with the removal 
of the finasteride arm. 
2.1 Study Objectives 
Revised overall age range of 
subjects in the setipiprant and 
placebo groups from 18 - 41 to 18 - 
49 years.  
Deleted finasteride arm. 
See rational above. 
3 Study Design 
Deleted finasteride arm.  
Deleted requirement for blinded 
investigator to give efficacy 
assessments to finasteride subjects 
while subject/staff are unblinded. 
 
 
 
Removed finasteride arm.  
4.1 Number of Subjects 
Deleted finasteride arm (n = 35); 
changed number of setipiprant and 
placebo subjects from 187 to 152. 
 
 
 
 
 
  
Removed the finasteride arm. 
Increased overall age range of 
subjects in the setipiprant and 
placebo groups from 18 - 41 to 18 - 
49 years. 

 
 
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Section 
Revision 
Rationale 
4.2 Study Population 
Characteristics 
Revised overall age range of 
subjects in the setipiprant and 
placebo groups from 18 - 41 to 18 - 
49 years.  
Noted that subjects were assigned to 
finasteride under the original 
protocol. 
To increase the rate of study 
enrollment. 
For clarification. 
4.3 Inclusion Criteria, 3 
Expanded the age range from 18 – 
41 years to 18 – 49 years. 
To be consistent with the revised 
study population. 
4.3 Inclusion Criteria, 6 
Revised the required maintenance 
of hair length from ≥ 2.54 cm (1 in) 
to ≥ 2 cm (0.75 in).  
To increase the rate of study 
enrollment 
4.4 Exclusion Criteria, 3 
The Criterion 3 list was re-lettered 
from 3a – e to 3a – f. 
Added a criterion. 
 
 
 
  
 
 
 
 
4.4 Exclusion Criteria, 4 
The Criterion 4 list was re-lettered 
from 4a–e to 4a-c 
Removed criteria. 
4.4 Exclusion Criteria; 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.5.3 Special Activities 
Deleted finasteride information. 
See rationale above. 
5.2 Control Treatments 
Deleted finasteride information. 
See rationale above. 
5.3 Methods for 
Masking/Blinding 
Deleted information about 
unblinded finasteride subjects/site 
staff and blinded investigator to 
perform efficacy assessments. 
See rationale above. 

 
 
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Section 
Revision 
Rationale 
5.4 Treatment 
Allocation Ratio and 
Stratification 
Deleted finasteride arm. Changed 
number of
 subjects from 
175 to 140. 
Changed the randomization ratio for 
 subjects from 2:2:1 
(setipiprant:placebo:finasteride) to 
1:1 (setipiprant:placebo). Added 
non-PK subjects to be stratified by 
age, 18 -34 and 35 – 49 years.  
To be consistent with Section 4.1 
5.5 Method for 
Assignment to 
Treatment 
Groups/Randomization 
Deleted finasteride arm (n = 35). 
Changed number of 
 
subjects from 175 to 140. Changed 
 randomization ratio from 
2:2:1 
(setipiprant:placebo:finasteride) to 
1:1 (setipiprant:placebo). 
To be consistent with Sections 4.1 
and 5.4. 
5.6 Treatment Regimen 
and Dosing 
Added subjects assigned to 
finasteride prior to protocol 
Amendment 1 should continue 
treatment until they complete the 
study. 
Deleted information about 
finasteride regimen. 
For clarification. 
5.7 Storage of Study 
Drugs 
Deleted information about 
finasteride risk to pregnant or 
potentially pregnant women 
See rationale above. 
5.9 Treatment 
Administration 
Deleted finasteride packaging, 
dosing, and open-label information. 
See rationale above. 
6.1 Efficacy Measures 
Deleted finasteride blinding 
information. 
See rationale above. 
 
 
. 
7.3 Hypothesis and 
Methods of Analysis 
Deleted pairwise comparison of 
finasteride and placebo. 
Added that finasteride subjects will 
be summarized alone. 
Finasteride arm was removed.  
To address how data from subjects 
treated with finasteride prior to 
protocol Amendment 1will be 
analyzed. 
7.3.1 Primary Efficacy 
Analyses 
Added finasteride subject data will 
be summarized alone. 
See rationale above. 
 
 
 
 
 

 
 
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Section 
Revision 
Rationale 
7.5 Sample Size 
Calculation 
Deleted finasteride arm (n = 35) and 
related text. 
Deleted Finasteride versus Placebo 
column from Table 2. 
Removed finasteride arm. 
 
 
 
 
 
 
 
 
 
8.3 Procedures for Final 
Study Entry 
Changed time subject has entered 
the study from time of 
randomization (Day 1) to screening. 
Correction as informed consent 
form is signed at screening. 
8.4 Instructions for the 
Subjects 
Deleted instructions for finasteride 
group. 
Removed finasteride arm. 
8.6 Compliance With 
Protocol 
Deleted finasteride bottle 
information. 
See rationale above. 
10.5.1 
Labeling/Packaging 
Deleted finasteride information. 
See rationale above. 
 

 
 
Approval Date: 
 
17-Feb-2017
ALLERGAN 
 
 
 
 
 
 
 
 
 
Date (DD/MMM/YYYY)/Time (PT) 
Signed by: 
Justification 
  
 
 
            
 
           
 
            
 
           
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
Protocol 1922-201-002 Amd 1