Clinical trial NCT03818256
Conditions: Antipsychotic-induced Weight Gain (AIWG)
Keywords: Antipsychotic-induced weight gain (AIWG) Obesity Weight Gain Mental disorders Schizophrenia Risperidone Quetiapine Olanzapine Bipolar Disorder
Sponsor: Corcept Therapeutics
Start date: 2019-12-04; Completion date: 2022-07-06
Enrollment: 71 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase 2, double blind, placebo-controlled, randomized study is to assess the safety, efficacy, and pharmacokinetics (PK) of miricorilant (CORT118335) in obese adults with schizophrenia or bipolar disorder treated with antipsychotic medications.

Detailed description:
This is a randomized, double-blind, placebo-controlled study that will assess the safety, efficacy, and PK of miricorilant in obese patients with schizophrenia or bipolar disorder who are currently taking oral or injectable atypical antipsychotic medication.

Patients who meet the criteria for the Study CORT118335-876 will be randomized on Day 1 to receive 600 mg miricorilant or placebo for 12 weeks.

Arms: arm 1: Patients who meet the entry criteria will be randomized to receive 600 mg miricorilant for 12 weeks. arm 2: Patients who meet the entry criteria will be randomized to receive placebo for 12 weeks.
Interventions: intervention 1: Miricorilant intervention 2: Placebo
Intervention descriptions: intervention 1: Miricorilant 600 mg (6 X 100 mg tablets) for once-daily oral dosing intervention 2: Placebo tablets for once-daily oral dosing

Protocol documents:
Prot_000.pdf: 
Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, 
Efficacy, and Pharmacokinetics of Miricorilant (CORT118335) in Obese Adult Patients with 
Schizophrenia or Bipolar Disorder and Recent Weight Gain While Taking Antipsychotic 
Medications (GRATITUDE) 
 
NCT Number: NCT03818256 
 
Date: 11 January 2022 




Protocol CORT118335-876 (GRATITUDE)
Corcept Therapeutics  
Amendment 5  |  11 January 2022 
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SPONSOR SIGNATURE PAGE 
Protocol Title 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study 
Evaluating the Safety, Efficacy, and Pharmacokinetics of 
Miricorilant (CORT118335) in Obese Adult Patients with 
Schizophrenia or Bipolar Disorder and Recent Weight Gain While 
Taking Antipsychotic Medications (GRATITUDE) 
Protocol Number 
CORT118335-876 
Version 
Amendment 5 
Date 
11 January 2022 
 
 
APPROVAL STATEMENT 
The undersigned has reviewed the format and content of the above protocol and approved 
for issuance.  


Protocol CORT118335-876 (GRATITUDE)
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PROTOCOL SYNOPSIS 
Name of Sponsor 
Corcept Therapeutics  
Name of Active Ingredient 
Miricorilant 
Study Number 
CORT118335-876 
Title of Study 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Efficacy, and 
Pharmacokinetics of Miricorilant (CORT118335) in Obese Adult Patients with Schizophrenia or 
Bipolar Disorder and Recent Weight Gain While Taking Antipsychotic Medications (GRATITUDE) 
Study Centers  
Approximately 35 sites in the US 
Phase of Development 
Phase 2 
Duration of Treatment 
Treatment duration of 12 weeks and study participation duration of ~20 weeks (up to 28 days for 
Screening, 12 weeks for Treatment and 4 weeks after last dose in Follow-up). 
Study Objectives 
Safety  
• To assess the safety of miricorilant with concurrent administration with an atypical antipsychotic 
medication. 
Primary Efficacy 
• To assess the efficacy of miricorilant compared with placebo in reversing recent antipsychotic-
induced weight gain (AIWG) caused by an atypical antipsychotic medication. 
Secondary Efficacy 
• To assess the efficacy of miricorilant in improving metabolic parameters associated with 
diabetes or cardiovascular morbidity. 
Pharmacokinetics 
• To assess the pharmacokinetics (PK) of miricorilant in patients with recent AIWG caused by an 
atypical antipsychotic medication. 
Population 
Patients with a body mass index (BMI) ≥30 kg/m2 who have started any FDA-approved oral or 
injectable atypical antipsychotic medication (except clozapine) for the treatment of schizophrenia or 
bipolar disorder within the last 18 months and have since shown an increase in body weight by ≥5% 
within 6 months of starting the antipsychotic medication as documented by medical record, treating 
physician’s report, or by an acceptable means of patient-documented weight gain. 
Number of Patients Planned 
Approximately 70 patients will be randomized 1:1 to receive 600 mg miricorilant or placebo in 
this study. 


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Methodology 
This is a randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, and PK of 
miricorilant in patients with schizophrenia or bipolar disorder and BMI ≥30 kg/m2 who have weight 
gain as a result of treatment with any oral or injectable atypical antipsychotic medication (except 
clozapine). 
The study consists of the following study periods: 
• Screening Period: up to 28 days 
• Treatment Period: Day 1 to Week 12 
• Follow-up Period: 28 days after last study dose  
The study design is shown schematically in Figure S1. 
Figure S1 
Schematic of Study Design 
 
Abbreviation: W, Week. 
 
Patients who are eligible for participation in the study will be randomized on Day 1 in a 1:1 ratio to 
600 mg miricorilant or placebo.  
Patients will be asked to volunteer for the PK substudy, and approximately 45 patients are expected to 
participate. The PK substudy will be conducted at the Week 4 visit. In patients who consent to 
participate in the PK substudy, blood samples will be collected according to the PK plan outlined in the 
study manual. 
Key Inclusion Criteria 
Patients eligible for enrollment into this study must meet the following criteria: 
• Are men or women ≥18 to ≤65 years old. 
• Able to successfully complete placebo-tablet swallow assessment. 
• Meet the criteria for schizophrenia based on medical history and the Mini International 
Neuropsychiatric Interview (MINI) or meet the criteria for bipolar disorder as described by the 
American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders 
(DSM-5) and the MINI.  
• Have started any FDA-approved oral or injectable atypical antipsychotic medication (except 
clozapine) for treatment of schizophrenia or bipolar disorder within 18 months of Screening. 
Patients with bipolar disorder will need to either be on monotherapy with an antipsychotic 
medication or have been on a stable dose of a mood stabilizer ≥3 months with a stable weight 


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and subsequently have an antipsychotic medication added that resulted in weight gain. Patients 
with bipolar disorder who are on a mood stabilizer must remain on a stable dose of their mood 
stabilizer throughout the study. 
• Have shown an increase in body weight of ≥5% above their prior body weight within 6 months 
of atypical antipsychotic medication initiation, as documented by medical records, physician’s 
report, or by an acceptable means of patient-documented weight gain. 
- Historical weights from medical records must be within 6 months prior to initiation of 
antipsychotic medication.  
o Patients who have had a treatment gap in their antipsychotic medication for ≥28 days 
but have restarted medication within 18 months of Screening are eligible to participate 
if they have documented increase in body weight of ≥5% within 6 months of restarting 
the antipsychotic medication. Historical weights will not be accepted for these patients. 
o Historical weights will not be accepted for patients with bipolar disorder on mood 
stabilizers. 
- Patients who document their own weight gain MUST show evidence of weight gain using 
one of the following methods: 1) using Smart Scale weight data, 2) using photographs to 
record weight displayed on a scale, or 3) using a weight diary.  
o Dates of weight collection need to be available for the weight gain documentation 
method used. 
 
The scale photograph must clearly show the scale and displayed weight. The 
photograph must show the date and time stamp for inspection and verification 
by the study staff. 
o Historical “prior body weight” before the initiation of their antipsychotic medication 
will not be accepted for patient-documented weight. 
• Have been on the same dose of oral or injectable atypical antipsychotic medication for the last 
month prior to Screening.  
• Are clinically stable and unlikely to require change to their antipsychotic medication 
(i.e. medication switch or dose change) through the duration of the study (20 weeks).  
• Patients with schizophrenia must have a Brief Psychiatric Rating Scale (BPRS) of ≤50 at 
Screening.  
• Patients with bipolar disorder must have a Young Mania Rating Scale (YMRS) of ≤20 and 
Montgomery-Åsberg Depression Rating Scale (MADRS-SIGMA) of ≤20 at Screening. 
• Have a BMI ≥30 kg/m2. 
Key Exclusion Criteria 
Patients who meet any of the following exclusion criteria will not be eligible to participate in the study:  
• Have psychiatric exclusion criteria: 
- An acute psychiatric condition that might require emergent intervention during the study. 
- A psychiatric hospitalization within the last 6 months prior to Screening. 
- Are currently at risk of suicide in the opinion of the Investigator or as confirmed by the 
following:  
o Answer “Yes” on items 4 or 5 (Columbia Suicide Severity Rating Scale [C-SSRS]-
ideation) with the most recent episode occurring within the last 6 months prior to 
Screening. 
o Answer “Yes” to any of the 5 items (C-SSRS-behavior) with an episode occurring 
within the last 6 months prior to Screening. 
• Have participated in another Corcept study with miricorilant. 
• Are currently taking the antipsychotic medication clozapine. 


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• Are currently taking the mood stabilizing medication carbamazepine. 
• Are currently taking more than one antipsychotic medication.  
• Have poorly controlled diabetes mellitus with glycated hemoglobin (HbA1c) >10% or a fasting 
blood glucose >200 mg/dL. 
• Have poorly controlled hypertension with a systolic blood pressure >170 mm Hg or a diastolic 
blood pressure >100 mm Hg by in-office blood pressure measurement. 
• Have a history of symptomatic hypotension with a systolic blood pressure <100 mm Hg or a 
diastolic blood pressure <60 mm Hg. 
• Have a recent history of orthostatic hypotension with a systolic blood pressure decrease of at 
least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within the last year 
of Screening. 
• Have a history of a seizure disorder. 
• Are currently using or plan to use prescription or over-the-counter weight-loss treatments during 
the study, including but not limited to*: 
- Olanzapine/samidorphan (Lybalvi) or other samidorphan drug combinations. 
- Prescription drugs such as orlistat (Xenical), phentermine (Adipex-P, Pro-Fast SA, Pro-Fast 
SR, Fastin, Oby-trim, Zantryl, Teramine, Phentride, Phentercot, Obephen, Oby-cap), 
phentermine/topiramate (Qsymia), liraglutide (Saxenda), semaglutide (Wegovy), or 
naltrexone HCl/bupropion HCl (Contrave). 
- Over-the-counter anti-obesity agents such as orlistat (Alli), herbal supplements or other 
alternative remedies (Cortislim, Dexatrim, Acutrim).  
*Patients currently taking these medications may participate in the study if appropriate to 
discontinue the medication, and if the patient is amenable to discontinuing the medication for a 
wash-out period of 5 half-lives prior to the baseline assessment. 
Note: Names within parenthesis are trademarks of third-party companies. 
• Are currently using any prohibited medications (Section 5.4.3). Prohibited medications must be 
discontinued at least 5 half-lives prior to a patient receiving their first study treatment. 
Administration of concomitant medications (Section 5.4) are at the discretion of the Investigator 
and/or Medical Monitor. 
• Have a history of a medical condition affecting body weight including but not limited to poorly 
controlled hyper- or hypothyroidism; eating disorder such as anorexia, bulimia, or binge eating; 
or polycystic ovary syndrome. 
• Have had weight-loss surgery including, but not limited to, gastric bypass, sleeve gastrectomy, 
gastric band placement, or biliopancreatic diversion with duodenal switch within the last 5 years 
prior to Screening or are planning weight-loss surgery during the study. 
• Have had liposuction within 1 year prior to Screening or have planned liposuction during the 
study. 
• Have any elective surgery planned during the study. 
• Have a clinically significant electrolyte abnormality at Screening.  
• Are currently using a medication such as digoxin with an increased risk for toxicity in the event 
of electrolyte changes. 
• Are taking an unstable dosage (change in the dose within 4 weeks prior to Screening) of a 
medication that may change the fluid or electrolyte status such as a diuretic. 
• Have AST or ALT >3 × the upper limit of normal. 


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Investigational Treatment, Dose, and Mode of Administration 
Study Drug: miricorilant 100 mg tablets 
Mode of Administration: Oral administration of miricorilant tablets. Patients should take tablets 
with food.  
Dose: 600 mg (6 × 100 mg tablets). All tablets should be taken at once and the patient should make 
every effort to take their miricorilant dose at the same time each day.  
Reference Product, Dose, and Mode of Administration 
Placebo tablets to match 100 mg miricorilant tablets. 
Mode of Administration: Oral administration of placebo tablets. Patients should take tablets with food.  
Dose: 6 placebo tablets daily. All tablets should be taken at once. 
Criteria for Evaluation 
Study endpoints corresponding to study objectives are listed below. 
Safety Endpoints 
• Incidence of adverse events (AEs), serious AEs (SAEs), and AEs leading to early 
discontinuation 
• Changes from Baseline in clinical laboratory tests (hematology and chemistry panels) at 
Week 12 
• Changes from Baseline in physical examinations and vital sign measurements at Week 12 
• Changes from Baseline in electrocardiogram parameters at Week 12  
Primary Efficacy Endpoint 
• Change from Baseline in body weight at Week 12 for 600 mg miricorilant versus placebo 
Secondary Efficacy Endpoints 
• Percentage of patients achieving a ≥5% weight loss from Baseline at Week 12 for 600 mg 
miricorilant versus placebo 
• Change from Baseline in waist-to-hip ratio at Week 12 for 600 mg miricorilant versus placebo 
• Change from Baseline in homeostatic model assessment for insulin resistance (HOMA-IR) at 
Week 12 for 600 mg miricorilant versus placebo  
Exploratory Endpoints 
• The following exploratory endpoints will be analyzed: 
• In all patients: 
- Change from Baseline in adrenocorticotropic hormone (ACTH) at Week 12 
- Change from Baseline in serum cortisol at Week 12 
• In patients with schizophrenia 
- Changes from Baseline in BPRS, C-SSRS, and Clinical Global Impression Scale (CGI) at 
Week 12 
• In patients with bipolar disorder 
- Changes from Baseline in C-SSRS, CGI, YMRS and the MADRS-SIGMA at Week 12 
• In patients with diabetes:  
- Change from Baseline in glycated hemoglobin (HbA1c) at Week 12 
- Change in fasting blood glucose at Week 12 
• In patients with high blood pressure: 
- Change from Baseline in blood pressure at Week 12 


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Pharmacokinetic Endpoints 
• Key PK parameters estimated from steady-state plasma concentrations 
Statistical Methods 
Sample Size 
Approximately 70 patients will be randomized 1:1 to treatment or placebo in this study. This sample 
size provides 90% power to detect a difference in body weight change of 4 kg between the 600 mg 
miricorilant dose group and the placebo group. Based on Larsen et al. 2017, which examined the effect 
of liraglutide on olanzapine-and clozapine-treated patients, as well as on other studies of AIWG 
summarized in Mizuno et al. 2014, a standard deviation (SD) of around 4 to 5 kg can be expected for 
the difference in body weight change between treatment groups. Accordingly, a SD of 4.5 kg is 
assumed here. Assuming a difference in body weight change between groups of 4 kg with an SD of 
4.5 kg, and setting α=0.05, 28 patients per group provides 90% power to detect a significant difference 
between active dose group and placebo after completing 12 weeks of treatment.  
Allowing for 20% dropouts increases the required sample size to 35 patients per group for a total of 
70 patients in the trial. 
With 35 patients receiving miricorilant 600 mg in the trial, there is a 83% chance that an uncommon 
AE (i.e., an AE expected to occur in only 1 in every 20 patients) will be observed at least once during 
the trial. If a specific AE is never seen in the trial, the 95% upper confidence bound on its true 
incidence would be 10%. 
Randomization will be stratified by the type of antipsychotic medication used (olanzapine, 
risperidone/paliperidone (active risperidone metabolite), quetiapine, aripiprazole, or other). If at least 
14 patients complete 12 weeks of treatment (7 patients treated with 600 mg miricorilant and 7 patients 
treated with placebo) in one of the allowed antipsychotic medications, this sample size provides 50% 
power to detect a difference in body weight change of 4 kg between 600 mg miricorilant and placebo, 
at alpha=0.1 level for that antipsychotic medication. 
Analysis Populations 
Analysis of the safety data will be performed on the Safety Population, defined as all patients who 
receive at least 1 dose of study medication. 
Analysis of the efficacy data will be performed on the Efficacy Evaluable (EE) Population, defined as 
all patients who receive ≥4 weeks of study medication and have Baseline and at least 1 body weight 
measurement taken on or after Week 4.  
Sensitivity analyses of the primary and other key endpoints will be performed on the Intent-to-Treat 
(ITT) Population, defined as all patients who receive at least 1 dose of study medication.  
Analysis of PK data will be performed on the PK Population, defined as all patients who have 
evaluable PK data. 
Safety Analyses 
An Independent Data Monitoring Committee (IDMC) will be established to conduct periodic reviews 
of data to ensure the safety of patients. 
Adverse events will be mapped to system organ classes and preferred terms using the Medical 
Dictionary for Regulatory Activities. Treatment-emergent AEs will be summarized overall and 
displayed by system organ class and preferred term, as well as by severity, seriousness, and relationship 
to study treatment. Serious AEs and AEs that lead to discontinuation of study treatment or withdrawal 
from the study will be listed by individual patient. 


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Clinical laboratory test results (chemistry and hematology), vital sign measurements, physical 
examination findings, and ECG results will be summarized by visit using descriptive statistics. Shift 
tables will be constructed that describe changes from Baseline in clinical laboratory values. 
Efficacy Analyses 
The primary efficacy endpoint is the change in body weight from Baseline to Week 12. The primary 
endpoint will be assessed using a mixed-effect model with repeated measures (MMRM) with change in 
body weight at each visit as the outcome variable; baseline body weight and antipsychotic medication 
(stratification factor) as covariates; and randomized treatment (600 mg miricorilant or placebo), visit, 
and treatment-by-visit interaction as fixed effects. The difference in body weight change between 
miricorilant and placebo will be estimated from the model along with its 95% confidence interval (CI). 
The MMRM used to assess the primary endpoint will be rerun as a sensitivity analysis using the ITT 
Population in place of the EE Population. 
The percentage of patients in each treatment group who lose ≥5% of their baseline body weight will be 
presented along with its 95% CI. In addition, a logistic regression model with baseline body weight and 
stratification factor as covariates will be used to compare miricorilant to placebo. 
HOMA-IR and waist-to-hip ratio will be analyzed using similar models as the primary analysis of body 
weight change. Both HOMA-IR and waist-to-hip ratio may be log-transformed prior to analysis; model 
estimates derived from log-transformed data will be back-transformed to the original scale for 
presentation.  
Pharmacokinetic Analyses 
The PK data obtained from the PK substudy, including the PK parameters of miricorilant will be 
presented. Additionally, plasma concentrations of miricorilant will be plotted over time. 


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CONTENTS 
CLINICAL STUDY PROTOCOL CORT118335-876 (GRATITUDE) ........................................ 1 
SPONSOR SIGNATURE PAGE ................................................................................................... 2 
PROTOCOL SYNOPSIS ............................................................................................................... 3 
CONTENTS .................................................................................................................................. 10 
List of Tables ................................................................................................................................ 16 
List of Figures ............................................................................................................................... 16 
List of Abbreviations and Definitions........................................................................................... 17 
1 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE ............................................................................................. 20 
1.1 
Therapeutic Area ............................................................................................................... 20 
1.1.1 Background ........................................................................................................... 20 
1.1.2 Therapeutic Hypothesis ........................................................................................ 20 
1.2 
Miricorilant: A Mixed Agonist/Antagonist of the Glucocorticoid-Receptor and Antagonist 
of the Mineralocorticoid-Receptor .................................................................................... 21 
1.2.1 Nonclinical Summary ........................................................................................... 21 
1.2.1.1 Pharmacology ........................................................................................ 21 
1.2.2 Absorption, Distribution, Metabolism, and Elimination ...................................... 24 
1.2.3 Safety Pharmacology and Toxicology .................................................................. 25 
1.3 
Clinical Summary ............................................................................................................. 26 
1.3.1 Phase 1 Study CORT118335-850 ......................................................................... 26 
1.3.2 Phase 1 Study CORT118335-851 ......................................................................... 29 
1.3.3 Phase 1 Study CORT118335-852 ......................................................................... 30 
1.3.4 Phase 1 Study CORT118335-853 ......................................................................... 31 
1.4 
Rationale for Study Design and Dose Regimen ............................................................... 31 
1.4.1 Differences Statement ........................................................................................... 31 
1.4.2 Design Considerations .......................................................................................... 31 
1.4.3 Rationale for Dose Selection and Regimen .......................................................... 32 
1.4.4 Rationale for Study Design ................................................................................... 32 
1.5 
Benefits and Risks............................................................................................................. 32 
2 
STUDY OBJECTIVES ..................................................................................................... 34 


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2.1 
Safety Objective ................................................................................................................ 34 
2.2 
Primary Efficacy Objective ............................................................................................... 34 
2.3 
Secondary Efficacy Objective ........................................................................................... 34 
2.4 
Pharmacokinetics Objective.............................................................................................. 34 
3 
STUDY DESIGN.............................................................................................................. 35 
3.1 
Overall Design .................................................................................................................. 35 
3.2 
Study Endpoints ................................................................................................................ 35 
3.2.1 Safety Endpoints ................................................................................................... 35 
3.2.2 Primary Efficacy Endpoint ................................................................................... 36 
3.2.3 Secondary Efficacy Endpoints .............................................................................. 36 
3.2.4 Exploratory Endpoints .......................................................................................... 36 
3.2.5 Pharmacokinetic Endpoint .................................................................................... 37 
3.3 
Number of Patients and Study Participation ..................................................................... 37 
3.3.1 Number of Patients ............................................................................................... 37 
3.3.2 Patient Study Completion ..................................................................................... 37 
3.4 
Definitions: End of Treatment, End of Study, and Study Duration .................................. 37 
3.4.1 End of Treatment .................................................................................................. 37 
3.4.2 End of Study ......................................................................................................... 37 
3.5 
Study Termination by Sponsor ......................................................................................... 37 
4 
STUDY POPULATION ................................................................................................... 38 
4.1 
Inclusion Criteria .............................................................................................................. 38 
4.2 
Exclusion Criteria ............................................................................................................. 39 
4.3 
Screen Failures .................................................................................................................. 41 
4.4 
Early Patient Discontinuation or Withdrawal ................................................................... 41 
4.4.1 Early Patient Discontinuation ............................................................................... 42 
4.4.2 Early Patient Withdrawal from Study ................................................................... 42 
4.5 
Replacement of Patients .................................................................................................... 42 
4.6 
Restrictions During Study ................................................................................................. 43 
5 
STUDY TREATMENTS AND MANAGEMENT .......................................................... 44 
5.1 
Study Drug and Placebo.................................................................................................... 44 


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5.2 
Safety Assessments ........................................................................................................... 45 
5.2.1 Monitoring of Liver Injury.................................................................................... 45 
5.2.2 Excessive GR/MR Antagonism ............................................................................ 45 
5.3 
Dose Adjustment Criteria ................................................................................................. 45 
5.3.1 Dose Reduction ..................................................................................................... 45 
5.3.2 Dose Interruption and/or Discontinuation: General Criteria ................................ 45 
5.3.3 Dose Interruption and/or Discontinuation: Special Safety Events ....................... 45 
5.4 
Concomitant Medications ................................................................................................. 49 
5.4.1 Permitted Concomitant Medications ..................................................................... 49 
5.4.2 Permitted Concomitant Therapy Requiring Caution ............................................ 49 
5.4.3 Prohibited Medications ......................................................................................... 50 
5.5 
Method of Treatment Assignment and Randomization .................................................... 50 
5.6 
Blinding............................................................................................................................. 50 
5.7 
Dose Diary ........................................................................................................................ 51 
5.8 
Product Accountability and Treatment Adherence ........................................................... 51 
5.9 
Independent Data Monitoring Committee to Monitor Patient Safety ............................... 51 
6 
DESCRIPTION OF STUDY ASSESSMENTS AND PROCEDURES AND 
APPROPRIATENESS OF MEASUREMENTS .............................................................. 52 
6.1 
Informed Consent and Screening ...................................................................................... 52 
6.2 
Placebo Tablet Swallow Assessment ................................................................................ 52 
6.3 
History............................................................................................................................... 52 
6.4 
Safety Measures ................................................................................................................ 52 
6.4.1 Physical Examination and Vital Signs .................................................................. 53 
6.4.2 Height .................................................................................................................... 53 
6.4.3 Electrocardiogram ................................................................................................. 53 
6.4.4 Adverse Events ..................................................................................................... 53 
6.4.5 Clinical Laboratory Assessments .......................................................................... 53 
6.4.5.1 Laboratory Parameters ........................................................................... 53 
6.4.5.2 Sample Collection, Preparation, and Shipping ...................................... 55 
6.4.5.3 Blood Volume Summary ....................................................................... 55 
6.5 
Efficacy Assessments........................................................................................................ 55 


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6.6 
Pharmacokinetic Assessments .......................................................................................... 55 
6.7 
Pharmacodynamic/Biomarker Assessments ..................................................................... 55 
6.8 
Clinician Assessed Outcomes ........................................................................................... 56 
6.9 
Appropriateness of the Measures ...................................................................................... 56 
7 
STUDY ASSESSMENTS AND PROCEDURES BY STUDY VISIT ............................ 57 
7.1 
Screening Period (Day-28 to Day-1) ................................................................................ 57 
7.2 
Baseline (Day 1) ............................................................................................................... 58 
7.3 
Treatment Period ............................................................................................................... 59 
7.3.1 Week 1: Study Day 8 (±2 Days) ........................................................................... 59 
7.3.2 Week 2: Study Day 15 (±2 Days) ......................................................................... 59 
7.3.3 Week 4: Study Day 29 (±2 Days) ......................................................................... 60 
7.3.4 Week 6: Study Day 43 (±2 Days) ......................................................................... 60 
7.3.5 Week 8: Study Day 57 (±2 Days) ......................................................................... 60 
7.3.6 Week 10: Study Day 71 (±2 Days) ....................................................................... 60 
7.3.7 Week 12: Study Day 85 (±2 Days) ....................................................................... 61 
7.4 
Early Termination Visit (In-Clinic Visit) ......................................................................... 61 
7.5 
Follow-Up Visit (In-Clinic Visit; 28±5 Days after Last Dose of Study Drug) ................ 62 
7.6 
Unscheduled Visits ........................................................................................................... 63 
8 
SAFETY EVENT DOCUMENTATION AND REPORTING ........................................ 64 
8.1 
Investigator’s Responsibilities .......................................................................................... 64 
8.2 
Monitoring Safety Data During the Study ........................................................................ 64 
8.3 
Definition of an Adverse Event ........................................................................................ 64 
8.4 
Definition of a Serious Adverse Event ............................................................................. 64 
8.5 
Expectedness ..................................................................................................................... 65 
8.6 
Clinical Significance ......................................................................................................... 65 
8.7 
Clinical Laboratory Adverse Events ................................................................................. 65 
8.8 
Documentation of Adverse Events ................................................................................... 65 
8.9 
Adverse Event Classification ............................................................................................ 66 
8.9.1 Intensity Grades of Adverse Events ...................................................................... 66 
8.9.2 Relationship of Adverse Event to Study Drug or Procedure ................................ 67 


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8.10 
Procedures for Reporting a Serious Adverse Event .......................................................... 67 
8.11 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as Adverse 
Events or Serious Adverse Events .................................................................................... 67 
8.12 
Adverse Event Follow-Up ................................................................................................ 67 
8.13 
Pregnancy .......................................................................................................................... 67 
8.13.1 Maternal Exposure ................................................................................................ 68 
8.13.2 Paternal Exposure ................................................................................................. 68 
8.14 
Treatment of Overdose ..................................................................................................... 68 
8.15 
Emergency Sponsor Contact ............................................................................................. 68 
9 
STATISTICAL METHODS ............................................................................................. 69 
9.1 
Analysis Populations ......................................................................................................... 69 
9.2 
Hypothesis Testing............................................................................................................ 69 
9.3 
Sample Size Calculation ................................................................................................... 69 
9.4 
Analysis Plan .................................................................................................................... 70 
9.4.1 Patient Disposition ................................................................................................ 70 
9.4.2 Demographic and Baseline Data ........................................................................... 70 
9.4.3 Concomitant Medications ..................................................................................... 70 
9.4.4 Safety Analyses ..................................................................................................... 70 
9.4.5 Efficacy Analyses ................................................................................................. 71 
9.4.5.1 Primary Efficacy Analysis ..................................................................... 71 
9.4.5.2 Sensitivity Analysis of Primary Endpoint.............................................. 71 
9.4.5.3 Secondary Efficacy Analyses ................................................................ 71 
9.4.6 Pharmacokinetic Analysis ..................................................................................... 72 
9.4.7 Exploratory Analysis ............................................................................................ 72 
9.4.8 Pharmacogenetic Analysis .................................................................................... 72 
9.4.9 Interim Analysis .................................................................................................... 72 
10 
ETHICAL AND LEGAL CONSIDERATIONS .............................................................. 73 
10.1 
Compliance with IRB Regulations ................................................................................... 73 
10.2 
Ethical Conduct of the Study ............................................................................................ 73 
10.3 
Protection of Human Patients ........................................................................................... 73 
10.3.1 Compliance with Informed Consent Regulations ................................................. 73 


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10.3.2 Patient Confidentiality .......................................................................................... 74 
10.3.3 Patient Privacy ...................................................................................................... 74 
11 
ADMINISTRATIVE CONSIDERATIONS ..................................................................... 75 
11.1 
Study Monitoring .............................................................................................................. 75 
11.2 
Quality Management ......................................................................................................... 75 
11.3 
Documentation .................................................................................................................. 75 
11.3.1 Case Report Forms and Study Records ................................................................ 75 
11.3.2 Access to Source Documentation ......................................................................... 76 
11.3.3 Source Documents ................................................................................................ 76 
11.3.4 Study Files and Retention of Study Records ........................................................ 76 
11.4 
Long-Term Retention of Biological Samples ................................................................... 77 
11.5 
Clinical Supplies ............................................................................................................... 77 
11.5.1 Inventory, Reconciliation, Return, and Disposition of Clinical Supplies ............. 77 
11.5.2 Clinical-Supply Inventory ..................................................................................... 77 
11.5.3 Return or Disposal of Study Drug and/or Supplies .............................................. 77 
11.6 
Drug Accountability.......................................................................................................... 78 
11.7 
Post-trial Care ................................................................................................................... 78 
11.8 
Noncompliance with the Protocol ..................................................................................... 78 
11.9 
Financial Disclosure.......................................................................................................... 79 
11.10 Publication and Disclosure Policy .................................................................................... 79 
11.11 Final Report Signature ...................................................................................................... 79 
12 
REFERENCES ................................................................................................................. 80 
13 
APPENDICES .................................................................................................................. 83 
Appendix A: Schedule(s) of Assessments .................................................................................... 84 
Appendix B: Summary of Changes .............................................................................................. 87 
 


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List of Tables 
Table 1 
Study Drug and Placebo: Formulation, Administration, Packaging, and Storage .44 
Table 2 
Criteria for Dose Modification or Discontinuation Due to Special Safety Events 46 
Table 3 
Permitted Concomitant Medications ......................................................................49 
Table 4 
Clinical Laboratory Variables Evaluated During the Study ..................................54 
Table 5 
Adverse Event Grades Based on the Common Terminology Criteria for 
Adverse Events ......................................................................................................66 
Table 6 
Causal Attribution Guidance for Adverse Events ..................................................67 
Table 7 
Definitions of Analysis Populations ......................................................................69 
Table 8 
Pharmacokinetic Variables for Analysis ................................................................72 
Table 9 
Schedule of Clinical Assessments and Procedures ................................................84 
Table 10 
Summary of Changes in Protocol CORT118335-876 Amendment 5 ...................88 
 
List of Figures 
Figure 1  
Effect of Miricorilant (CORT118335) on Body Weight in Female Rats Given 
Olanzapine .............................................................................................................23 
Figure 2  
Reversal of Olanzapine-Induced Weight Gain in Female Rats .............................24 
Figure 3 
CORT118335-876 Study Design ...........................................................................35 
 


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List of Abbreviations and Definitions 
Abbreviation 
Definition 
ACTH 
adrenocorticotropic hormone 
AE 
adverse event 
AIWG 
antipsychotic-induced weight gain 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANCOVA 
analysis of covariance 
AR 
androgen receptor 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BMI 
body mass index 
BCRP 
breast cancer resistance protein 
BPRS 
Brief Psychiatric Rating Scale 
CFR 
Code of Federal Regulations 
CGI 
Clinical Global Impression 
CI 
confidence interval 
Cmax 
maximum concentration 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DSM-5 
Fifth edition of the Diagnostic and Statistical Manual of Mental Disorders 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EE 
efficacy evaluable 
ET 
early termination 
FDA 
(United States) Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
GR 
glucocorticoid receptor 
HbA1c 
glycated hemoglobin 
hERG 
human ether-á-go-go-related gene 


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Abbreviation 
Definition 
HIPAA 
Health Information Portability and Accountability Act 
HME 
hot melt extrudate 
HOMA-IR 
homeostatic model assessment for insulin resistance 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 
IV 
intravenous 
IWRS 
interactive web response system 
Ki 
inhibition constant 
MADRS-SIGMA 
Structured Interview Guide for the Montgomery-Åsberg Depression Rating Scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
MINI 
Mini International Neuropsychiatric Interview 
MR 
mineralocorticoid receptor 
NCI 
National Cancer Institute 
NOAEL 
no-observed-adverse-effect level 
PK 
pharmacokinetic(s) 
PR 
progesterone receptor 
QTc 
corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s equation: QTcF=QT/(RR⅓) 
SAE 
serious adverse event 
SD 
standard deviation 
SDD 
spray dried dispersion 
SoA 
schedule of assessments 
T4 
thyroxine 
TAT 
tyrosine aminotransferase 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum concentration 
TSH 
thyroid-stimulating hormone 
UGT1A1 
uridine diphosphate glucuronosyltransferase 1A1 
US 
United States 


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Abbreviation 
Definition 
WBC 
white blood cell (count) 
YMRS 
Young Mania Rating Scale 


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1 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
1.1 
Therapeutic Area 
Antipsychotic-induced weight gain (AIWG) is the condition in which patients with 
schizophrenia, bipolar disorder, or other conditions treated with antipsychotic medications gain 
weight.  
There are currently no approved treatments for AIWG; adjunctive pharmacological treatment, 
behavioral therapy, and antipsychotic medication switch have limited efficacy (Maayan et al. 
2010, Mukundan et al. 2010, Mizuno et al. 2014). Dietary counseling and exercise programs 
have shown only modest effects on weight in these patients (Dayabandara et al. 2017). The 
investigational product miricorilant (CORT118335) has shown efficacy in rat models of AIWG 
and is expected to provide benefit in patients with AIWG. 
1.1.1 Background 
Atypical antipsychotic medications were initially developed to address the extrapyramidal effects 
and tardive dyskinesia seen with first-generation antipsychotic medications. These medications, 
while efficacious, cause significantly more weight gain in patients than the first-generation 
medications. Though all antipsychotic medications cause some amount of weight gain, the 
atypical antipsychotics (clozapine and olanzapine, followed by risperidone and quetiapine) 
appear to cause the most weight gain (ADA/APA/AACE/NAASO 2004). Olanzapine and 
clozapine cause between 4.0 to 4.5 kg of weight gain on a standard dose over the course of 
10 weeks (Allison and Casey 2001). Weight gain is of concern in the background of increasing 
rates of obesity and diabetes among the general population, since both are risk factors for 
cardiovascular disease.  
In addition to weight gain, antipsychotic medications also increase insulin resistance, cholesterol, 
and serum triglycerides, significantly increasing cardiovascular risk in this patient population 
(Dayabandara et al. 2017). Patients with schizophrenia treated with antipsychotics have 
increased risk of mortality (2–3 times above that of the general population), which corresponds 
to a 10 to 25 year reduction in life expectancy, largely due to increased cardiovascular disease 
(Laursen et al. 2012). In patients with bipolar disorder as well, treatment with atypical 
antipsychotic medications such as olanzapine, clozapine, quetiapine, and risperidone is 
associated with weight gain (McIntyre et al. 2003, Narasimhan et al. 2007, Torrent et al. 2008, 
Nashed et al. 2011). The weight gain can exacerbate other associated health risks such as 
compromised neurocognitive function or can increase obesity-related metabolic disorders in this 
patient population (McIntyre et al. 2003, Nashed et al. 2011). Weight gain in patients with 
schizophrenia or bipolar disorder is also associated with discontinuation of antipsychotic 
medications (Liebermann et al. 2005; Torrent et al. 2008), which could lead to a decrease in their 
overall effectiveness.  
1.1.2 Therapeutic Hypothesis 
The pathogenesis of weight gain from taking antipsychotic medications is not well understood. 
Antipsychotic medications act on a multiple neuroreceptors and may increase appetite and 


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decrease energy expenditure (Gothelf et al. 2002, Graham et al. 2005). Dysregulation of the 
hypothalamic-pituitary-adrenal axis has been implicated with the use of atypical antipsychotics. 
Rats treated with clozapine showed an increase in corticosterone (Tulipano et al. 2007).  
A role for the glucocorticoid receptor (GR) has been suggested in AIWG. In healthy volunteers 
treated with olanzapine or risperidone, mifepristone, a GR antagonist, ameliorated weight gain 
associated with the antipsychotic medication (Gross et al. 2009, Gross et al. 2010). Miricorilant, 
which is a mixed agonist/antagonist of the GR and an antagonist of the mineralocorticoid 
receptor (MR) has shown to be effective in a rat model of AIWG (Hunt et al. 2012). 
1.2 
Miricorilant: A Mixed Agonist/Antagonist of the Glucocorticoid-Receptor and 
Antagonist of the Mineralocorticoid-Receptor 
Miricorilant is a new molecular entity that is a mixed agonist/antagonist of the GR and an 
antagonist of the MR, and is being developed for the treatment of AIWG. The goals of this study 
(CORT118335-876 [GRATITUDE]) are to evaluate the safety, efficacy, and pharmacokinetics 
(PK) of miricorilant in reversing AIWG in patients taking any FDA-approved oral or injectable 
atypical antipsychotic medication (except clozapine) for the management of schizophrenia or 
bipolar disorder. 
Detailed information about miricorilant is provided in the Investigator’s Brochure (IB). This 
section summarizes the key data that are relevant to this study. 
1.2.1 Nonclinical Summary 
1.2.1.1 
Pharmacology 
This section summarizes in vitro and in vivo data relating to the pharmacology of miricorilant as 
a mixed agonist/antagonist of the GR. In most models, mifepristone was used as an active 
comparator. Mifepristone is an antagonist of the progesterone receptor (PR), androgen receptor 
(AR), and GR. Miricorilant has similar GR antagonism without effects at the PR or AR. 
1.2.1.1.1 In Vitro Pharmacology 
Miricorilant is a high-affinity mixed agonist/antagonist of cortisol at the GR. In a fluorescence 
polarization ligand-binding assay to assess affinity for GR, miricorilant had a Ki of 0.5 nM. 
Functional antagonism was assessed by measuring the ability of miricorilant to prevent a 
dexamethasone-induced increase in the activity of tyrosine aminotransferase (TAT). The 
expression of the TAT gene is regulated by GR, and a GR agonist such as dexamethasone 
increases gene expression, protein production, and enzyme activity. For routine screening, the 
human liver carcinoma cell line Hep-G2 and the rat hepatoma cell line H4-II-EC4 were used. 
Miricorilant is a full antagonist in the human Hep-G2 cell line, with no evidence of agonist 
activity, but does not achieve complete antagonism in the rat H4-II-EC4 cell line. When tested in 
the absence of dexamethasone, miricorilant acted as partial agonist in the rat cell line. In a 
reporter gene assay that assessed the ability of miricorilant to inhibit the dexamethasone-induced 
increase in luciferase expression, miricorilant behaved as a full antagonist, with a Ki of 24 nM 
(Hunt et al. 2012). GR antagonism was assessed using a protein:protein interaction assay, which 


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assesses activation of a nuclear hormone receptor by measuring the interaction of a full-length 
nuclear hormone receptor with a nuclear fusion protein, and miricorilant had a Ki of 118 nM.  
1.2.1.1.2 In Vivo Pharmacology 
Three studies (MPI 950-033, MPI 950-034, and MPI 950-035) have been conducted to evaluate 
the ability of miricorilant, at various doses, to prevent weight gain in female rats (10 per group) 
administered the antipsychotic medication olanzapine and fed a normal diet. The most 
commonly used animal model of antipsychotic-induced weight gain involves the administration 
of olanzapine to female rats. Several authors have reported differential effects of olanzapine 
depending on the diet used, the route, frequency and duration of drug administration, and the sex 
of the animals (reviewed in Van der Zwaal 2014). Olanzapine leads to a robust and reproducible 
increase in body weight in female rats, but results in male rats are less reliable. Thus, female rats 
were used in the studies reported here. In all 3 studies, olanzapine was administered by oral 
gavage at a dose of 1.2 mg/kg twice a day, 12 hours apart (i.e., 2.4 mg/kg/day, for 21 consecutive 
days). This series of studies shows a dose-dependent ability of miricorilant to prevent 
olanzapine-induced increases in body weight, food consumption, and abdominal fat content in 
female rats (Miricorilant IB).  
Of these 3 studies, MPI 950-035 (Hunt et al. 2012) investigated the lowest doses of miricorilant. 
At doses above 2 mg/kg/day in combination with olanzapine, or 0.6 mg/kg/day alone, 
miricorilant reduced basal body weight (Figure 1).  


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Figure 1  
Effect of Miricorilant (CORT118335) on Body Weight in Female Rats Given 
Olanzapine 
  
Source: Hunt 2012 
Abbreviation: O, olanzapine. 
 
The ability of miricorilant to reverse (rather than prevent) olanzapine-induced weight gain in 
female rats was investigated in 3 separate studies. In the first study (MPI 950-144) rats were fed 
a normal diet and administered olanzapine at a dose of 1.2 mg/kg twice a day, 
(i.e., 2.4 mg/kg/day, for 56 consecutive days). A control group (n=12), that received only vehicle 
throughout the duration of the study, was also included. 
A statistically significant increase in body weight was observed in all rats treated with olanzapine 
during the induction phase, and this effect was maintained for the duration of the study in rats 
that received only vehicle in the treatment phase (Figure 2). Miricorilant at all doses completely 
abrogated the olanzapine-induced increase in body weight gain and food consumption. The 
effects noted with a total daily dose of 2 mg/kg, regardless of whether this was administered as a 
single dose of 2 mg/kg (noted below as Mid Dose QD) or a split dose of 1 mg/kg twice a day 
(noted below as Low Dose BID), were very similar. Effects were observed from the first week of 
dosing and then throughout the remainder of the study.  


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Figure 2  
Reversal of Olanzapine-Induced Weight Gain in Female Rats 
 
Source: MPI 950-144 
Olanzapine: 2.4 mg/kg/day; CORT118335 Low Dose=1 mg/kg; CORT118335 Mid Dose=2 mg/kg; CORT118335 
High Dose=10 mg/kg 
 
The administration of olanzapine to female rats fed a high-fat diet results in a rapid increase in 
body weight, with a statistically significant effect noted by Day 5. The ability of miricorilant to 
reverse the effects of olanzapine in this model has been investigated in two studies 
(RenaSci RS1738 and RS1854), and doses as low as 0.5 mg/kg/day fully reverse the effects of 
olanzapine. These results provide additional support for the potential utility of miricorilant in the 
treatment of AIWG in patients. 
1.2.2 Absorption, Distribution, Metabolism, and Elimination 
The plasma protein binding of miricorilant in rat and human was >99.9% (Corcept PK-118335-
008) and in mouse and monkey was >99% (Corcept PK-118335-013). 
In vitro studies with human cytochrome P450 (CYP) isoforms indicated that miricorilant was 
metabolized almost exclusively by CYP2C19 (94%) (Corcept PK-118335-012). Miricorilant also 
exhibited inhibitory potential of CYP3A4, CYP2C8, CYP2C9, uridine diphosphate 
glucuronosyltransferase 1A1 (UGT1A1), and breast cancer resistance protein (BCRP) in vitro 
(Corcept PK-118335-004, Corcept PK-118335-009, and Sygnature Discovery TPT-125281-
118335-002). 


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Fecal elimination represented the principal route of elimination with 98.7% ± 2.48% recovered. 
1.2.3 Safety Pharmacology and Toxicology 
The nonclinical safety of miricorilant has been evaluated in preliminary ascending single- and 
repeat-dose studies followed by Good Laboratory Practice (GLP) 28-day and 91-day repeat-dose 
toxicology studies in mice and monkeys. Dose range finding reproductive toxicology studies 
have been conducted in mice and rabbits. In addition, standard packages of GLP safety 
pharmacology studies (in vitro human ether-à-go-go related gene [hERG] assay, cardiovascular 
effects in monkeys, respiratory function in mice, and neurobehavioral effects in mice) and 
genotoxicity studies (in vitro bacterial and mammalian cell assays; in vivo assay in mice), have 
been completed. All safety pharmacology and toxicology studies used oral administration, the 
intended clinical route. Miricorilant was not genotoxic in any study. There were no adverse 
findings in any safety pharmacology study up to the highest dose studied (500 mg/kg in mice, 
400 mg/kg in monkeys). In the GLP hERG assay, 0.9 μM miricorilant (the highest concentration 
studied, limited by solubility) produced maximum inhibition of hERG-mediated potassium 
currents of 23.8%. 
Mouse and monkey 28- and 91-day general GLP toxicology studies have been completed with 
miricorilant as follows: 
• Mice were administered doses of 30, 100, 300, or 500 mg/kg daily by oral gavage for 
28 days. No adverse effects were observed at any dose in this study, therefore the no 
observed adverse effect level (NOAEL) was 500 mg/kg. The NOAEL was associated 
with a Day 28 miricorilant area under the curve (AUC)0-24 of 36,184 ng∙h/mL in male 
mice and 36,896 ng∙h/mL in female mice (MPI 950-126). 
• Monkeys were administered doses of 20, 100, or 400 mg/kg daily by oral gavage for 
28 days. No adverse effects were observed at any dose in this study, so the NOAEL was 
400 mg/kg. The NOAEL was associated with a Day 28 miricorilant AUC0-24 of 
9,006 ng∙h/mL in male monkeys and 7,030 ng∙h/mL in female monkeys (MPI 950-127). 
• Mice were administered doses of 30, 100, or 500 mg/kg daily by oral gavage for 91 days. 
No adverse effects were observed at any dose in the study and the NOAEL was 
considered to be 500 mg/kg. The NOAEL was associated with a Day 91 AUC0-24 of 
34,230 ng∙h/mL in male mice and 37,950 ng∙h/mL in female mice (MPI 950-140). 
• Monkeys were administered doses of 20, 50, or 200 mg/kg daily by oral gavage for 
91 days. No adverse effects were noted in female monkeys, and the NOAEL was 
200 mg/kg, which was associated with an AUC0-24 of 30,145 ng∙h/mL on Day 1 and an 
AUC0-24 of 19,465 ng∙h/mL on Day 91. In male monkeys, the NOAEL was 50 mg/kg 
since adverse clinical effects, specifically abnormal feces, decreased activity, lack of 
appetite, hunched posture, dehydration and ataxia, were noted at the highest dose. The 
NOAEL was associated with a Day 1 AUC0-24 of 19,937 ng∙h/mL and a Day 91 
AUC0-24 of 3,813 ng∙h/mL (MPI 950-139). 
Other treatment-related findings in the nonclinical studies are considered related to the mode of 
action of miricorilant as a GR and MR antagonist. Although the risk of clinically significant 
safety concerns is considered to be low, potential adverse effects of miricorilant, based on the 
pharmacological effect of GR antagonists, may include signs and symptoms consistent with 


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excessive GR antagonism (e.g., weakness, tiredness, dizziness, orthostatic hypotension, 
hypoglycemia, dehydration, nausea, vomiting, diarrhea, and muscle aches). Potential adverse 
events of miricorilant, based on the pharmacological effects of an MR antagonist, may include 
signs and symptoms of excessive MR antagonism (e.g., hyperkalemia or hypotension).  
Reproductive toxicity studies have been completed in mice and rabbits as follows: 
• In the preliminary dose range finding study in mice, miricorilant was administered daily 
by oral gavage from gestation day (GD) 6 through 15 at doses of 0 (vehicle), 10, 30, 100 
and 300 mg/kg/day. No test article-related effects were observed on maternal survival, 
clinical observations, or maternal macroscopic evaluations at necropsy. No effects of 
miricorilant were observed on fetal sex ratios or fetal body weights. Test article-related 
maternal effects were observed at all dose levels evaluated. Test article-related fetal 
external malformations of cleft palate were observed at all dose levels evaluated. 
Additionally, the malformation exencephaly was observed in 2 fetuses in 1 litter at the 
100 mg/kg/day dose. The relationship of this finding to miricorilant is unclear. 
• In the preliminary dose range finding study in rabbits, miricorilant was administered 
daily by oral gavage from GD 7 through 19 at doses of 0 (vehicle), 3, 10, 30 and 
100 mg/kg/day. No clear miricorilant-related effects were observed on maternal survival, 
food consumption, maternal macroscopic observations, or number of corpora lutea at any 
of the dose levels evaluated. Miricorilant-related maternal effects were observed at doses 
≥10 mg/kg/day in this study. No effects of miricorilant were observed on fetal external 
evaluations at 3 and 10 mg/kg/day. Miricorilant related effects at doses above 
10 mg/kg/day included adverse pregnancy outcomes, such as abortions. 
Preliminary non-GLP prenatal development studies conducted in mice and rabbits suggest that 
miricorilant should not be administered to pregnant women due to adverse effects on fetal 
development (mice) or adverse pregnancy outcomes (rabbits). 
Women of childbearing potential and men with partners of childbearing potential in clinical 
studies must use a highly efficacious form of birth control as outlined in Section 4.1. 
More information is provided in the current Miricorilant IB. 
1.3 
Clinical Summary 
Clinical experience in humans with miricorilant is derived from four Phase 1 studies conducted 
in healthy adult subjects (Studies CORT118335-850, CORT118335-851, CORT118335-852, and 
CORT118335-853):  
Available safety and PK data from these studies are presented in this section. 
1.3.1 Phase 1 Study CORT118335-850 
CORT118335-850, the first-in-human study of miricorilant, was an adaptive-dose, 
single-ascending dose (SAD) and multiple-ascending dose (MAD) study of the safety, 
tolerability, PK, and food/pharmacological effects of orally administered miricorilant in male 
and female healthy subjects. 
Drug product was administered as a hot melt extrudate (HME) capsule, a suspension of 
spray-dried dispersion (SDD) with vehicle in bottle, or as a 100 or 300 mg tablet. The HME 


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capsule and 300 mg tablet led to lower than expected miricorilant exposures and will not be 
evaluated further in clinical development. Thus, only the efficacy, safety, and PK results of the 
suspension (SDD) and 100 mg tablet formulations are summarized below.  
In the SAD portion of the study, miricorilant was administered under fasting conditions as 100, 
300, 900, or 1500 mg. The SAD suspension portion of the study also evaluated 900 mg 
miricorilant administered under fed conditions with a high-fat breakfast versus 900 mg 
miricorilant administered under fasting conditions. 
In the MAD dose portion of the study, miricorilant was administered once-daily under fasting 
conditions for 14 days as 150, 450, or 900 mg in suspension. 
In addition, 2 × 100 mg miricorilant tablets and 2 × 300 mg miricorilant tablets were evaluated 
under fasting and fed conditions. 
Safety Results 
Drug-Related Treatment-Emergent Adverse Events 
Across all SAD/suspension cohorts, 1 of 7 (14.3%) fasted and 1 of 1 (100%) fed placebo subjects 
reported one or more TEAEs. Of subjects treated with miricorilant, the proportion reporting at 
least 1 TEAE ranged from 0 to 60% across all doses. No trend in the proportion reporting TEAEs 
with dose was apparent. In the MAD/suspension part of the study, 4 of 8 (50.0%) placebo treated 
subjects reported at least 1 TEAE. Across all doses of miricorilant, 3 of 8; 33.3% (150 mg and 
450 mg) or 3 of 9; 37.5% (900 mg) subjects reported at least 1 TEAE. In the food-effect 
(FE)/suspension part of the study, 3 subjects reported 4 TEAEs, none of which were considered 
related to treatment. 
Serious Adverse Events 
One serious adverse event (SAE) was reported in Study CORT118335-850. One subject 
experienced a non-fatal, acute myocardial infarction 28 days after a single oral dose of 
miricorilant 300 mg in suspension. The event was not considered related to study drug, but more 
likely related to the subject’s underlying coronary artery disease. 
No deaths were reported during the study.  
Adverse Events Leading to Discontinuation 
No AEs leading to discontinuation were reported.  
Vital Signs, Laboratory Evaluations, and Physical Examinations 
There were no clinically significant findings in any of the vital signs or laboratory evaluations. 
During physical examinations, a mild cardiac murmur was observed at the follow-up 
examination in a subject who had been treated with a single dose of miricorilant 900 mg in 
suspension under both fasted and fed conditions. The finding was not noted on previous 
examinations; the Investigator considered this asymptomatic finding most likely to be a 
pre-existing condition and not related to study drug. 
12-Lead Electrocardiogram 
Electrocardiograms (ECGs) were obtained in triplicate in the MAD/suspension parts of the 
study. Single ECGs were obtained in the SAD/suspension and FE/suspension parts of the study 


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unless abnormalities were detected. No subject recorded QT interval corrected for heart rate 
using Fridericia’s equation (QTcF) intervals that were >450 msec at any time point and no 
subject had increases in QTcF interval from baseline that were >30 msec. 
Holter Electrocardiogram: Exposure-Response Analysis 
In Study CORT118335-850, across the wide range of miricorilant doses/exposures evaluated, the 
majority of subjects recorded mean QTcF intervals that were ≤450 msec at all time points; those 
that did not were only slightly outside this range, with none exceeding 500 msec and none 
reported as clinically significant. Based on the totality of data, miricorilant does not have a 
clinically relevant effect on the QTc interval. 
Pharmacokinetic Results 
Plasma concentrations of miricorilant increased in an approximately dose-proportional manner 
following single-dose administration of 100 to 900 mg under fasting conditions, and in less than 
dose-proportional increases for doses of 900 or 1500 mg of the SDD-suspension formulation. 
Based on the concentration-time profile following administration of single 100 or 300 mg doses, 
the terminal half-life of miricorilant was estimated to be approximately 21 to 23 hours. 
Administration of 900 mg miricorilant suspension under fed conditions (with a high-fat 
breakfast) resulted in substantial increases in plasma concentrations versus fasting 
administration, with geometric mean (coefficient of variation [CV%]) relative bioavailability 
values (fed versus fasting) of 245% (24.5%) based on the maximum concentration (Cmax) and 
345% (28.8%) based on Cmax and AUC0-inf.  
In the MAD portion of the study, following once-daily administration of miricorilant suspension 
under fasting conditions for 14 days, the plasma concentrations of miricorilant increased in an 
approximately dose-proportional manner. The overall accumulation ratio (AUC0-tau) were 2.17 
for the 150 mg dose, 1.81 for the 450 mg dose, and 2.40 for the 900 mg dose.  
Following a single oral administration of 200 mg miricorilant (2 × 100 mg tablet) in the fasted 
state, the mean miricorilant Cmax, AUC24, and AUCinf were 105 ng/mL, 996 ng∙h/mL, and 
1790 ng∙h/mL respectively. These were contained within the exposures observed following the 
100 and 300 mg miricorilant doses. Based on the previously observed Part 4 (SAD/suspension) 
PK data, and the dose-proportional increases in miricorilant exposures to 900 mg (suspension), 
the exposures of 200 mg miricorilant (fasted), was modestly lower than expected. The geometric 
mean Cmax of 105 ng/mL for 200 mg miricorilant (2 × 100 mg tablets) is approximately 25% 
lower versus predicted Cmax of 140 ng/mL based on dose-proportionality.  
Following administration of 200 mg miricorilant (2 × 100 mg tablets) under fed conditions (with 
a high-fat breakfast), miricorilant Cmax, AUClast and AUCinf increased by 1.8-, 2.2- and 2.1-fold, 
respectively, compared to 200 mg miricorilant administered under fasting conditions. 
Efficacy Results 
This study was designed to evaluate safety and PK and was not powered to detect efficacy. There 
was no notable difference between miricorilant- and placebo-treated subjects in mean change 
from baseline in body weight, and no clinically significant individual laboratory values. 


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1.3.2 Phase 1 Study CORT118335-851 
CORT118335-851 was an open-label study conducted with [14C]-miricorilant to assess the 
absolute bioavailability (Part 1) and the mass balance recovery, absorption, metabolism and 
elimination, and metabolite profile and identification (Part 2) of miricorilant in healthy male 
subjects. 
Subjects were healthy men, aged 18 to 65 years (Part 1) and 30 to 65 years (Part 2), with a body 
mass index (BMI) in the range of 18.0 to 30.0 kg/m2. In Part 1, 6 subjects received a single oral 
dose of 900 mg miricorilant in suspension followed by a microdose (100 µg) of 
[14C]-miricorilant containing a microtracer amount of 14C given as an intravenous infusion. 
In Part 2, 6 subjects received a single oral dose of 150 mg [14C]-miricorilant oral solution in 
caprylic acid. 
Safety results 
Drug-Related Treatment-Related Adverse Events 
No TEAEs were reported in Part 1 of the study. In Part 2 of the study, 5 of 6 subjects reported at 
least 1 TEAE; only 1 TEAE (upper abdominal pain) was considered possibly related to 
miricorilant. 
Serious Adverse Events 
No SAEs were reported in Study CORT118335-851. 
Adverse Events Leading to Discontinuation 
No AEs leading to discontinuation were reported in Study CORT118335-851. 
Pharmacokinetic Results 
PK analysis in Part 1 (absolute bioavailability) was performed in 6 subjects who received a 
single oral dose of 900 mg miricorilant in suspension under fasting conditions and a microdose 
of 100 μg miricorilant containing a [14C] microtracer by intravenous infusion. The geometric 
mean absolute bioavailability of miricorilant was determined to be 16.9%.  
PK analysis in Part 2 (mass balance) was performed in 6 subjects who received a single oral 
administration of 150 mg [14C]-miricorilant as a solution in caprylic acid (5 mL) under fed 
conditions. (Note: Exposure with this formulation was higher than that observed in Study 
CORT118335-850 for the same dose of the suspension). Following administration of this single 
oral dose of 150 mg [14C]-miricorilant, total [14C]-radioactivity was quantifiable in whole blood 
in all subjects for 2‒12 hours and remained so for 12‒24 hours postdose. Plasma concentrations 
of total radioactivity were evident for 1‒4 hours postdose. Maximum plasma concentrations 
occurred 2‒12 hours postdose. Concentrations then declined in a biphasic manner and 
remained quantifiable for between 24 and 48 hours postdose. In comparison with the total 
[14C]-radioactivity observed in plasma, the total [14C]-radioactivity observed in whole blood was 
lower at all time points where radioactive levels were detectable. The whole blood:plasma 
concentration ratio based on total [14C]-radioactivity ranged from 0.613‒0.763. Administration 
of a single oral dose of 150 mg [14C]-miricorilant resulted in the majority of total radioactivity 
being recovered in the feces (mean, 89.1%), with much lower amounts (mean, 4.6%) in the 
urine. These results suggest that the predominant route of elimination is hepatic. 


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1.3.3 Phase 1 Study CORT118335-852 
CORT118335-852 is a two-part, single-center, double-blind, randomized, placebo-controlled 
assessment of the effect of the miricorilant, 100 mg tablets (as 600 mg [6 × 100 mg tablets] and 
900 mg [9 × 100 mg tablets given as a divided dose]) on weight gain induced by multiple doses 
of 10 mg olanzapine in healthy male subjects.  
In Part 1, 66 subjects received 10 mg daily of olanzapine for 14 days and were randomized in a 
1:1 ratio to receive 600 mg of miricorilant tablets daily or placebo. Part 1 is complete and final 
unblinded data are available. In Part 2, 30 subjects received 10 mg daily of olanzapine for 
14 days and were randomized in a 4:1 ratio to receive 900 mg of miricorilant tablets daily 
(600 mg in the morning and 300 mg in the evening) or placebo. Part 2 is complete and final 
unblinded data are available.  
Safety Results 
No deaths or SAEs were reported in this study.  
All subjects participating reported at least 1 TEAE. The majority of these TEAEs were attributed 
by the Investigator to the coadministered olanzapine (122 of the 150 TEAEs in the pooled 
placebo group, 85 of the 109 TEAEs in the 600 mg miricorilant group, and 53 of the 74 TEAEs 
in the 900 mg group). Only one subject had a severe TEAE in the placebo group of Part 1 
(described below); the majority of TEAEs reported were mild.  
In Part 1, 6 subjects were withdrawn early due to moderate or severe elevations in 
aminotransferases: 1 subject was administered miricorilant and olanzapine (1 moderate 
elevation) and 5 subjects were administered with placebo and olanzapine (1 severe and 
4 moderate elevations).  
Two subjects in Part 2 of the Study were withdrawn early due to moderate elevations in 
aminotransferases: 1 subject was administered with miricorilant and olanzapine and the other 
subject was administered with placebo and olanzapine. 
All TEAEs of elevated aminotransferases resolved following discontinuation of treatment; none 
had features of drug-induced liver injury (DILI) and subjects were asymptomatic. 
Efficacy Results 
In Part 1, healthy subjects administered olanzapine plus 600 mg of miricorilant gained less 
weight than subjects receiving olanzapine plus placebo. In addition, markers of liver damage that 
often rise temporarily at the start of olanzapine therapy increased less sharply in subjects 
receiving miricorilant, suggesting that miricorilant may have protective effects in the liver.  
Part 2 confirmed the weight mitigation results of Part 1. In Part 2, subjects treated with 
miricorilant showed statistically significantly smaller increases in triglycerides than the 
placebo group. 
Pharmacokinetic Results 
In Part 1, following once daily administration of miricorilant, 100 mg tablets at a total daily dose 
of 600 mg (6 × 100 mg tablets QAM only), the geometric mean (geometric CV%) AUC0-24, 
Cmax, and C24 were 6,680 (46.9) ng∙h/mL, 494 (40.6) ng/mL, and 153 (67.4) ng/mL, respectively. 


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In Part 2, following twice daily administration of miricorilant, 100 mg tablets at a total daily dose 
of 900 mg (6 × 100 mg tablets QAM plus 3 × 100 mg tablets QPM), the geometric mean 
(geometric CV%) AUC0-24, Cmax, and C24 were 17000 (41.9) ng∙h/mL, 958 (38.4) ng/mL, and 
547 (56.4) ng/mL, respectively. 
1.3.4 Phase 1 Study CORT118335-853  
This is an ongoing Phase 1, single-center, randomized, single-and multiple-dose study to assess 
the safety, tolerability, and PK of the miricorilant,150 mg tablet formulation proposed for use in 
future Phase 2 studies. 
Safety Results 
As of June 25, 2020, no deaths or SAEs have been reported in this ongoing study. 
Pharmacokinetic Results: 
In Cohort 1 (n=6) and cohort 2 (n=9), miricorilant tablets were administered, under fed 
conditions, as a single oral dose of 300 mg (2 × 150 mg tablets) or 900 mg (6 × 150 mg tablets), 
respectively. Preliminary PK data from both cohorts indicate that administration of the 
miricorilant tablet, 150 mg tablet under fed conditions provides generally similar miricorilant 
exposures as the miricorilant, 100 mg tablet under fed conditions (data from 
Study CORT118335-850), on a dose normalized basis. 
1.4 
Rationale for Study Design and Dose Regimen 
Antipsychotic-induced weight gain is the condition in which patients taking antipsychotic 
medications gain weight. As a result, patients are at increased risk for cardiovascular morbidity 
and mortality thought to be related to the increased incidence of metabolic syndrome. 
Approximately half of patients who take antipsychotic medications are obese (Annamalai 2017). 
There are currently no approved treatments for AIWG, and adjunct pharmacological treatment, 
behavioral therapy, and antipsychotic medication switch have limited efficacy. Miricorilant has 
shown efficacy in rat models of AIWG and is expected to provide benefit in patients with 
AIWG. This study is being conducted because GR antagonism has previously been shown to 
prevent weight gain in healthy volunteers taking olanzapine or risperidone (Gross et al. 2009, 
Gross et al. 2010). 
1.4.1 Differences Statement 
This is the first Phase 2 study with miricorilant to evaluate its ability to treat AIWG caused by 
any oral or injectable atypical antipsychotic medication (except clozapine) in obese patients with 
schizophrenia or bipolar disorder who have recently gained weight. Patients will have been on 
their antipsychotic medication for 18 months or less and have demonstrated weight gain within 
6 months of starting the antipsychotic medication.  
1.4.2 Design Considerations 
This is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety, 
efficacy, and PK of miricorilant. This study will be conducted in the USA, at approximately 
35 sites, and will randomize approximately 70 patients with schizophrenia or bipolar disorder 


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who have recent AIWG (see Section 4.1, exclusion criterion #6) in a 1:1 ratio to 600 mg 
miricorilant or placebo.  
The study will consist of 4 weeks of screening, 12 weeks of treatment, and 4 weeks of follow-up. 
Routine assessments of safety will consist of AE monitoring, measurement of vital signs, 
recording 12-lead ECG, physical examination, and clinical laboratory safety tests. Samples will 
be collected to determine standard PK parameters for miricorilant for patients who participate in 
the PK substudy. 
1.4.3 Rationale for Dose Selection and Regimen 
Single doses of miricorilant have been well tolerated up to doses of 2700 mg and multiple doses 
have been well tolerated up to 900 mg daily for 14 days. The dose chosen for this study are based 
on results from nonclinical studies in rats, in which miricorilant showed reversal of weight 
gained while on olanzapine (MPI 950-033, MPI 950-034, and MPI 950-035). In a Phase 1, 
placebo-controlled study in healthy volunteers, miricorilant administered at 600 mg once daily 
for 14 days demonstrated efficacy in mitigating olanzapine-induced weight gain (Study 
CORT118335-852, summarized in Section 1.3.3). CORT118335-876 is designed to evaluate the 
safety, efficacy, and PK of miricorilant to treat recent AIWG in patients with schizophrenia or 
bipolar disorder with the same lower dose (600 mg) of miricorilant used in Study CORT118335-
852. 
1.4.4 Rationale for Study Design 
This is the first study with miricorilant in obese patients with AIWG. Miricorilant, which is a 
mixed agonist/antagonist of the GR and an antagonist of the MR, has been shown to be effective 
in a rat model of AIWG (Hunt et al. 2012) and there is evidence that suggests GR antagonism 
may alleviate AIWG. In healthy volunteers treated with olanzapine or risperidone, mifepristone 
(a GR antagonist) ameliorated weight gain associated with the antipsychotic medication (Gross 
et al. 2009, Gross et al. 2010). The current study is powered to compare miricorilant and placebo, 
to determine whether once daily dosing of miricorilant for 12 weeks results in improvement of 
weight gain in patients with schizophrenia or bipolar disorder who are taking any FDA-approved 
oral or injectable atypical antipsychotic medication (except clozapine) for the management of 
schizophrenia or bipolar disorder. 
This study is placebo controlled to account for the effects of trial participation, and patients will 
be randomized to treatment or placebo in a double-blind manner to reduce bias. Miricorilant will 
be compared to placebo for safety, efficacy, and PK results. 
1.5 
Benefits and Risks 
Miricorilant has shown efficacy in rat models of AIWG and is expected to provide benefit in 
patients with AIWG. Weight gain is especially of concern in the background of increasing rates 
of obesity and diabetes among the general population, both risk factors for cardiovascular disease 
and early death. Patients with schizophrenia have an increased risk of mortality 2 to 3 times 
above that of the general population, which corresponds to a 10‒25-year reduction in life 
expectancy, largely due to increased cardiovascular disease (Laursen et al. 2012). In patients 
with bipolar disorder as well, treatment with atypical antipsychotic medications such as 


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olanzapine, clozapine, quetiapine, and risperidone is associated with weight gain (McIntyre et al. 
2003, Narasimhan et al. 2007, Torrent et al. 2008, Nashed et al. 2011). The weight gain can 
exacerbate other associated health risks such as compromised neurocognitive function or can 
increase obesity-related metabolic disorders in this patient population (McIntyre et al. 2003, 
Nashed et al. 2011). Reversal or possibly prevention of AIWG is expected to provide a clinically 
meaningful improvement in general health outcomes and life expectancy in this population. 
Based on the totality of data for miricorilant, the potential for clinically relevant drug-drug 
interactions in this study is minimal. In general, the class of atypical antipsychotic medications 
has the potential to undergo drug-drug interactions that are mediated predominately by CYP1A2, 
CYP2D6, and/or CYP3A4. Importantly, miricorilant does not affect the activity of CYP1A2 and 
CYP2D6, and in vitro data indicate that any inhibitory effect of miricorilant on CYP3A4 in vivo 
would be expected to be only weak-to-moderate (Corcept PK-118335-004). Additionally, there 
is no evidence that GR antagonism interferes with the efficacy of antipsychotic medications. 
The potential for drug-drug interactions between miricorilant and mood stabilizer medications is 
minimal, except for carbamazepine. In general, mood stabilizer medications are not expected to 
affect the activity of CYP2C19, the enzyme primarily responsible for the elimination of 
miricorilant. Furthermore, mood stabilizer medications are primarily eliminated renally and/or 
are glucuronidated; only carbamazepine is primarily metabolized by CYP3A4, for which 
miricorilant has shown inhibitory potential in vitro. 
Potential adverse effects of miricorilant may include signs and symptoms consistent with 
excessive GR antagonism (e.g., weakness, tiredness, dizziness, orthostatic hypotension, 
hypoglycemia, dehydration, nausea, vomiting, diarrhea, and muscle aches) and excessive 
mineralocorticoid receptor (MR) antagonism (e.g., hyperkalemia and hypotension).  
Many atypical antipsychotic medications have both orthostatic hypotension and drug induced 
leukopenia/neutropenia as reported adverse reactions. In clinical trial experience, events of 
leukopenia/neutropenia have been reported temporally related to antipsychotic agents. Patients 
who are at risk for clinically significant leukopenia/neutropenia or clinically significant 
orthostatic hypotension will be excluded from the study. Orthostatic hypotension will be 
measured at each study visit, including follow-up. 
Patients will be closely monitored during the study. Standard safety tests including orthostatic 
vital signs and chemistry panels (refer to Table 4) will be done at each study visit including 
follow-up as outlined in the Schedule of Assessments (SoA) (Appendix A); additional safety 
tests can be performed at the discretion of the Corcept Medical Monitor. 
The effects of any excessive GR or MR antagonism should be reversible by the administration of 
intravenous (IV) or oral hydrocortisone and intravenous fluids (IVF). Further information for 
monitoring and treating excessive GR or MR antagonism is provided in Section 5.2.2 and 5.3.3. 


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2 
STUDY OBJECTIVES 
2.1 
Safety Objective 
• To assess the safety of miricorilant with concurrent administration with an atypical 
antipsychotic medication. 
2.2 
Primary Efficacy Objective 
• To assess the efficacy of miricorilant compared with placebo in reversing recent AIWG 
caused by an atypical antipsychotic medication. 
2.3 
Secondary Efficacy Objective 
• To assess the efficacy of miricorilant in improving metabolic parameters associated with 
diabetes or cardiovascular morbidity. 
2.4 
Pharmacokinetics Objective 
• To assess the PK of miricorilant in patients with recent AIWG caused by an atypical 
antipsychotic medication. 


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3 
STUDY DESIGN 
3.1 
Overall Design 
This is a randomized, double-blind, placebo-controlled multicenter study to evaluate the safety, 
efficacy, and PK of miricorilant in obese patients (BMI ≥30 kg/m2) with schizophrenia or bipolar 
disorder who have recent AIWG caused by any FDA-approved oral or injectable atypical 
antipsychotic medication (except clozapine). 
The study consists of the following study periods: 
• Screening Period: up to 28 days 
• Treatment Period: Day 1 to Week 12 
• Follow-up Period: 28 days after last study dose  
 
The study design is illustrated in Figure 3. 
Figure 3 
CORT118335-876 Study Design 
 
Abbreviation: W, week. 
 
Patients who are eligible for participation in the study will be randomized on Day 1 in a 1:1 ratio 
to 600 mg miricorilant or placebo.  
Patients will be asked to volunteer for the PK substudy, and approximately 45 patients are 
expected to provide PK samples as part of this substudy. The PK substudy will be conducted at 
the Week 4 visit. In those patients who consent to participate in the substudy, blood samples will 
be collected according to the PK plan outlined in the study manual. 
3.2 
Study Endpoints 
3.2.1 Safety Endpoints 
The following endpoints will be summarized to assess the safety of miricorilant: 
• Incidence of AEs, SAEs, and AEs leading to early discontinuation 


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• Changes from Baseline in clinical laboratory tests (hematology and chemistry panels) at 
Week 12 
• Changes from Baseline in physical examinations and vital sign measurements at Week 12 
• Changes from Baseline in ECG parameters at Week 12 
3.2.2 Primary Efficacy Endpoint 
The following endpoints will be used to evaluate the primary objective of assessing the efficacy 
of miricorilant compared with placebo in reversing AIWG caused by an atypical antipsychotic 
medication: 
• Change from Baseline in body weight at Week 12 for 600 mg miricorilant versus placebo 
3.2.3 Secondary Efficacy Endpoints 
The following endpoints will be used to evaluate the secondary objective of assessing the 
efficacy of miricorilant in improving parameters associated with diabetes or cardiovascular 
morbidity 
• Percentage of patients achieving a ≥5% weight loss from Baseline at Week 12 for 600 mg 
miricorilant versus placebo 
• Change from Baseline in waist-to-hip ratio at Week 12 for 600 mg miricorilant versus 
placebo 
• Change from Baseline in HOMA-IR at Week 12 for 600 mg miricorilant versus placebo 
3.2.4 Exploratory Endpoints 
The following exploratory endpoints will be analyzed: 
In all patients: 
• Change from Baseline in adrenocorticotropic hormone (ACTH) at Week 12 
• Change from Baseline in serum cortisol at Week 12 
In patients with schizophrenia: 
• Changes from baseline in Brief Psychiatric Rating Scale (BPRS), Columbia-Suicide 
Severity Rating Scale (C-SSRS), and Clinical Global Impression Scale (CGI) at Week 12 
In patients with bipolar disorder: 
• Changes from Baseline in C-SSRS, CGI, Young Mania Rating Scale (YMRS), and the 
Structured Interview Guide for the Montgomery-Åsberg Depression Rating Scale 
(MADRS-SIGMA) at Week 12 
In patients with diabetes:  
• Change from Baseline in glycated hemoglobin (HbA1c) at Week 12 
• Change in fasting blood glucose at Week 12 
In patients with high blood pressure: 
• Change from Baseline in blood pressure at Week 12 


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3.2.5 Pharmacokinetic Endpoint 
The following endpoint will be summarized to meet the study PK objective of assessing the PK 
of miricorilant in patients with AIWG: 
• Key PK parameters estimated from steady-state plasma concentrations 
3.3 
Number of Patients and Study Participation 
3.3.1 Number of Patients 
Approximately 70 patients will be randomized in this study, with a target of randomizing 
35 patients in each treatment group: 600 mg miricorilant and placebo. See Section 9.3 for details 
regarding sample size calculation. See Section 4.5 for details regarding replacement of patients. 
Approximately 45 patients are expected to participate in the PK substudy. Patients who consent 
to participate in the PK substudy but do not provide adequate samples may be replaced. 
3.3.2 Patient Study Completion 
The maximum expected duration of a patient’s participation is 20 weeks (4 weeks of screening, 
12 weeks of treatment, and 4 weeks of follow-up). Patients are considered to have completed the 
study if they complete the treatment phase of the study, including the Week 12 visit. 
3.4 
Definitions: End of Treatment, End of Study, and Study Duration  
3.4.1 End of Treatment 
The end of treatment is defined as the date on which the patient received his or her last study 
treatment, which may be the end of the Treatment Period if the patient completed all treatments 
or may be earlier if the patient discontinued study treatment before the designated stopping point. 
3.4.2 End of Study 
The end of study is defined as the date of last contact (i.e., visit, telephone, e-mail) with any 
study patient. Corcept will ensure that the Institutional Review Board (IRB) is notified that the 
study has finished according to Corcept’s standard operating procedures and/or local or national 
regulations. 
3.5 
Study Termination by Sponsor 
If Corcept, Investigator, Study Monitor, or regulatory officials discover conditions arising during 
the study that indicate that the study should be halted or that a study site’s participation should be 
terminated, this action may be taken after appropriate consultation between Corcept and 
Investigator. Conditions that may warrant termination of the study include, but are not limited to, 
the following: 
• Discovery of an unexpected, serious, or unacceptable risk to patients enrolled in the study 
• Decision on the part of Corcept to suspend or discontinue testing, evaluation, or 
development of the product 
Study termination and follow-up will be performed in compliance with applicable regulations. 


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4 
STUDY POPULATION 
The following eligibility criteria are designed to select patients with schizophrenia or bipolar 
disorder, and a BMI ≥30 kg/m2 who have started any FDA-approved oral or injectable atypical 
antipsychotic medication (except clozapine) for the treatment of schizophrenia or bipolar 
disorder within the last 18 months prior to Screening and have since shown increase in body 
weight by ≥5% within 6 months of antipsychotic medication initiation either documented by 
medical records, treating physician’s report, or by an acceptable means of patient-documented 
weight gain; and for whom protocol treatment is considered appropriate. All relevant medical 
and nonmedical conditions will be taken into consideration when deciding whether this protocol 
is suitable for a particular patient. 
4.1 
Inclusion Criteria 
Patients eligible for enrollment into this study must meet the following criteria: 
1. Have provided informed consent. 
2. Are men or women ≥18 to ≤65 years old. 
3. Are able to successfully complete placebo-tablet swallow assessment. 
4. Meet the criteria for schizophrenia based on medical history and the Mini International 
Neuropsychiatric Interview (MINI) or meet the criteria for bipolar disorder as described 
by the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental 
Disorders (DSM-5) and the MINI.  
5. Have started any FDA-approved oral or injectable atypical antipsychotic medication 
(except clozapine) for treatment of schizophrenia or bipolar disorder within 18 months 
of Screening. Patients with bipolar disorder will need to either be on monotherapy with 
an antipsychotic medication or have been on a stable dose of a mood stabilizer for 
≥3 months with a stable weight and subsequently have an antipsychotic medication added 
that resulted in weight gain. Patients with bipolar disorder who are on a mood stabilizer 
must remain on a stable dose of their mood stabilizer throughout the study.  
6. Have shown an increase in body weight of ≥5% above their prior body weight within 
6 months of atypical antipsychotic medication initiation, as documented by medical 
records, physician’s report, or by an acceptable means of patient-documented weight 
gain.  
a. Historical weights from medical records must be within 6 months prior to initiation of 
antipsychotic medication.  
i. 
Patients who have had a treatment gap in their antipsychotic medication for 
≥28 days but have restarted medication within 18 months of Screening are 
eligible to participate if they have documented increase in body weight of ≥5% 
within 6 months of restarting the antipsychotic medication. Historical weights 
will not be accepted for these patients. 
ii. 
Historical weights will not be accepted for patients with bipolar disorder on 
mood stabilizers. 
b. Patients who document their own weight gain MUST show evidence of weight gain 
using one of the following methods: 1) using Smart Scale weight data, 2) using 
photographs to record weight displayed on a scale, or 3) using a weight diary.  


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i. 
Dates of weight collection need to be available for the weight gain 
documentation method used. 
• The scale photograph must clearly show the scale and displayed weight. 
The photograph must show the date and time stamp for inspection and 
verification by the study staff. 
ii. 
Historical “prior body weight” before the initiation of their antipsychotic 
medication will not be accepted for patient-documented weight.  
7. Have been on the same dose of oral or injectable atypical antipsychotic medication for 
the last month prior to Screening. 
8. Are clinically stable and unlikely to require changes to their antipsychotic medication 
(i.e. medication switch or dose change) through the duration of the study (20 weeks). 
9. Have a BMI ≥30 kg/m2. 
10. Patients with schizophrenia must have a BPRS of ≤50 at Screening. 
11. Patients with bipolar disorder must have a YMRS of ≤20 and MADRS-SIGMA of ≤20 
at Screening. 
12. Agree to use a highly effective method of contraception throughout the study and for at 
least 28 days after the last dose of assigned treatment (if a woman of childbearing 
potential or a man with a sexual partner of childbearing potential; see Section 4.6). Men 
with partners of childbearing potential must agree to use 2 forms of contraception, one of 
which is a double barrier method. Men must also agree to avoid sperm donation during 
the study and for at least 28 days after the final treatment administration. 
4.2 
Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible to participate in the study: 
1. Have psychiatric exclusion criteria: 
a. An acute psychiatric condition that might require emergent intervention during 
the study. 
b. A psychiatric hospitalization within the last 6 months prior to Screening. 
c. Are currently at risk of suicide in the opinion of the Investigator or as confirmed by 
the following: 
i. 
Answer “Yes” on items 4 or 5 (C-SSRS-ideation) with the most recent episode 
occurring within the last 6 months prior to Screening. 
ii. 
Answer “Yes” to any of the 5 items (C-SSRS-behavior) with an episode 
occurring within the last 6 months prior to Screening. 
2. Have participated in another Corcept study with miricorilant. 
3. Are currently taking the antipsychotic medication clozapine. 
4. Are currently taking the mood stabilizing medication carbamazepine. 
5. Are currently taking more than one antipsychotic medication. 
6. Have poorly controlled diabetes mellitus with HbA1c >10% or a fasting blood glucose 
>200 mg/dL. 
7. Have poorly controlled hypertension with a systolic blood pressure >170 mm Hg or a 
diastolic blood pressure >100 mm Hg by in-office blood pressure measurement. 
8. Have a history of symptomatic hypotension with a systolic blood pressure <100 mm Hg 
or a diastolic blood pressure <60 mm Hg. 


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9. Have a recent history of orthostatic hypotension with a systolic blood pressure decrease 
of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within 
the last year prior to Screening. 
10. Have a history of a seizure disorder. 
11. Are currently using or plan to use prescription or over-the-counter weight-loss treatments, 
including but not limited to*: 
a. Olanzapine/samidorphan (Lybalvi) or other samidorphan drug combinations. 
b. Prescription drugs such as orlistat (Xenical), phentermine (Adipex-P, Pro-Fast SA, 
Pro-Fast SR, Fastin, Oby-trim, Zantryl, Teramine, Phentride, Phentercot, Obephen, 
Oby-cap), phentermine/topiramate (Qsymia), liraglutide (Saxenda), semaglutide 
(Wegovy), or naltrexone HCl/bupropion HCl (Contrave). 
c. Over-the-counter anti-obesity agents such as orlistat (Alli), herbal supplements or 
other alternative remedies (Cortislim, Dexatrim, Acutrim). 
*Patients currently taking these medications may participate in the study if appropriate to 
discontinue the medication, and if the patient is amenable to discontinuing the medication 
for a wash-out period of 5 half-lives prior to the baseline assessment. 
Note: Names within parenthesis are trademarks of third-party companies. 
12. Are currently using any prohibited medications (Section 5.4.3). Prohibited medications 
must be discontinued at least 5 half-lives prior to a patient receiving their first study 
treatment. Administration of concomitant medications (Section 5.4) are at the discretion 
of the Investigator and/or Medical Monitor. 
13. Have a history of a medical condition affecting body weight including but not limited to 
poorly controlled hyper- or hypothyroidism; eating disorder such as anorexia, bulimia, or 
binge eating; or polycystic ovary syndrome. 
14. Have had weight-loss surgery including, but not limited to, gastric bypass, sleeve 
gastrectomy, gastric band placement, or biliopancreatic diversion with duodenal switch 
within the last 5 years prior to Screening or are planning weight-loss surgery during the 
study. 
15. Have had liposuction within 1 year prior to Screening or have planned liposuction during 
the study. 
16. Have any elective surgery planned during the study. 
17. Have the following laboratory abnormalities: 
a. Serum sodium ≤130 mmol/L or ≥145 mmol/L. 
b. Serum potassium ≤3.5 mEq/L or ≥5.1 mEq/L. 
c. Estimated glomerular filtration rate <60 mL/min/1.73m2. 
d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × the upper 
limit of normal. 
e. White blood cell count (WBC) below the limit of normal.  
f. Absolute neutrophil count <1,500 neutrophils/µL. 
18. Have a clinically significant electrolyte abnormality at Screening.  
19. Are currently using a medication such as digoxin with an increased risk for toxicity in the 
event of electrolyte changes. 
20. Are taking an unstable dosage (change in the dose within 4 weeks prior to Screening) of a 
medication that may change the fluid or electrolyte status such as a diuretic.  


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21. Have a clinically significant ECG abnormality as judged by the Investigator. 
22. Have a QTcF >450 ms for men or QTcF >470 ms for women. 
23. Are breast feeding, or pregnant, or planning a pregnancy. 
24. Have any clinical condition or significant concurrent disease judged by the Investigator to 
complicate the evaluation of the study treatment. 
25. Previous exposure to investigational drugs taken within 3 months or 5 half-lives of the 
investigational drug prior to Screening, whichever is longer. 
26. Are employees or immediate family members of the clinical site staff or Corcept 
employees. 
27. Have a current or prior history within the last 12 months of severe alcohol-use disorder, 
severe tobacco-use disorder, or severe cannabis use disorder as defined by the fifth 
edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 
28. Have a history of illicit drug use within the last 12 months including but not limited to 
cocaine, heroin, ecstasy, lysergic acid diethylymide (LSD) or other hallucinogens, and 
ketamine. 
29. Are seropositive for, hepatitis B or hepatitis C. 
30. Patients with a known HIV infection. 
31. Have an allergic reaction or hypersensitivity to miricorilant tablets. 
4.3 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomly assigned to study treatment. 
Patients who have an exclusionary laboratory, ECG, or vital sign result on initial screening tests 
may have that assessment repeated once within the 28-day screening period if the Investigator 
believes the result was spurious or otherwise confounded. 
Individuals who do not meet the criteria for participation in this study (screen failure) because of 
laboratory abnormalities alone may be rescreened at the discretion of the Investigator in 
discussion with the Medical Monitor. Rescreened patients should be assigned a new patient 
number. Rescreened patients should meet all of the entry criteria outlined in Sections 4.1 and 4.2. 
4.4 
Early Patient Discontinuation or Withdrawal  
In this study, patient “discontinuation” refers to early discontinuation of study treatment while 
remaining on study; that is, the patient may wish to stop treatment early but may agree to 
continue with study visits and/or assessments. 
Early patient “withdrawal” refers either to patient withdrawal of consent to any further study 
participation or to an Investigator/Sponsor decision to permanently withdraw the patient and 
cessation of all study treatments, procedures, and assessments without further follow-up. If a 
patient wishes to withdraw consent to further participation in the study entirely, this should be 
clearly documented (1) in the patient’s medical record and signed by the Investigator and (2) in 
the clinical study database (electronic case report form [eCRF]). 


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4.4.1 Early Patient Discontinuation  
Study treatment may be discontinued in the event of any of the following occurrences: 
• Unacceptable toxicity. 
• The Investigator decides it is in the patient’s best interest to discontinue treatment and/or 
participation in the study. Reasons may include the following: 
– The patient requires prohibited medications. 
– The patient is not compliant with protocol requirements. 
• Patient becomes pregnant. 
If a patient discontinues early from the study drug, that patient will complete an Early 
Termination (ET) visit at the time of the last dose of the study drug, or soon thereafter. The 
Follow-Up visit will be conducted 28±5 days after the last dose of the study drug. Investigators 
should encourage these patients to continue with all study visits and/or assessments per the 
patient’s original study schedule through Week 12 (end-of-treatment). If the Follow-Up visit 
coincides with any other study visit, the assessments performed at these visits will be combined. 
If a patient is unable to continue with all study visits, they will be encouraged to complete the 
end-of treatment Week 12 visit at the very least, in addition to the ET and Follow-Up visits. The 
date when the patient discontinues treatment and the reason for discontinuation must be recorded 
on the eCRF. 
For guidelines about temporary interruption of treatment, see Section 5.3. 
4.4.2 Early Patient Withdrawal from Study 
A patient may be withdrawn early from the study for the following medical or administrative 
reasons: 
• Withdrawal of consent. 
• Noncompliance, including refusal of the study treatment and/or failure to adhere to the 
study requirements, as specified in protocol. 
• Early termination of the study by Corcept. 
The date the patient is withdrawn from the study and the primary reason for withdrawal must be 
recorded on the eCRF. 
Patients may withdraw voluntarily from the study at any time. For patients who withdraw 
consent to participate in the study, every effort should be made to determine whether the 
withdrawal of consent was related to an AE or a specific aspect of the study. 
4.5 
Replacement of Patients 
Patients who withdraw from study early may be replaced, at the discretion of Corcept and 
the Investigator, to ensure that sufficient patients complete the study to achieve the objectives. 
A patient who is withdrawn because of AEs considered related to study medication will not 
be replaced. 


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4.6 
Restrictions During Study 
The following restrictions apply to patients in this study (prohibited or limited-use medications 
are described in Section 5.4):  
Dietary Restrictions: Patients will be asked to follow a healthy diet according to the American 
Heart Association guidelines (AHA 2018). 
Alcohol: Patients will be advised to limit alcohol use (also see Section 4.2 regarding alcohol 
consumption). 
Pregnancy: Miricorilant should not be administered to pregnant women due to adverse effects 
on fetal development (mice) or adverse pregnancy outcomes (rabbits). Therefore, women of 
childbearing potential must not become pregnant during this study. Men and women of 
childbearing potential who participate in this study must agree to use effective contraception.  
a. Highly effective forms of contraception include: 
i. Abstinence 
[Abstinence is only acceptable as true abstinence (i.e., when this is in line with 
the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., 
calendar, ovulation, symptothermal, post-ovulation methods), declaration of 
abstinence for the duration of a study, and withdrawal are not acceptable 
methods of contraception.] 
ii. Intrauterine device or intrauterine system 
iii. Oral contraceptive plus a barrier method 
iv. Diaphragm with vaginal spermicidal cream 
v. Vaginal spermicide with a condom  
vi. Surgical sterilization (≥6 months postsurgery)  
b. A patient is of childbearing potential if, in the opinion of the Investigator, she is 
biologically capable of having children and is heterosexually active. 
i. Women who are not of childbearing potential meet at least 1 of the following 
criteria: 
• Have undergone a documented hysterectomy and/or bilateral 
oophorectomy. 
• Have medically confirmed ovarian failure or have reached 
postmenopausal status, defined as cessation of regular menses for at least 
12 consecutive months with no alternative pathological or physiological 
cause and have a serum follicle stimulating hormone (FSH) level within 
the laboratory’s reference range for ovarian failure or postmenopausal 
women. 
Activity: Patients will be advised to continue their normal activity level and avoid excessive 
exertion beyond their normal activities. 


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5 
STUDY TREATMENTS AND MANAGEMENT 
5.1 
Study Drug and Placebo 
Study drug and placebo equivalent, including dose and regimen, formulation, packaging, and 
storage, are described in Table 1. A placebo tablet dosage form is developed to match the 
miricorilant 100-mg tablets. 
Table 1 
Study Drug and Placebo: Formulation, Administration, Packaging, 
and Storage 
Specifications 
Miricorilant 
Placebo 
Description 
Miricorilant tablets are white to off-white 
in color. 
Placebo tablets are white to off-white 
in color. 
Unit Dose Strength 
Miricorilant 100-mg tablets. 
Matching placebo tablets. 
Dose levels 
600 mg 
Placebo equivalent. 
Administration 
Orally, with 8 oz (240 mL) of water. Take 
with food. 
Orally, with 8 oz (240 mL) of water. Take 
with food. 
Regimen 
6 tablets, once daily at approximately the 
same time each day a. Swallow tablets 
whole. Do not chew, crush, cut, or 
dissolve the tablets. 
6 tablets, once daily at approximately the 
same time each day a. Swallow tablets 
whole. Do not chew, crush, cut, or 
dissolve the tablets. 
Dispensing study drug 
Dispense to patients according to their 
visit schedule. 
Dispense to patients according to their 
visit schedule. 
Missed doses 
If the patient remembers they missed a 
dose within 12 hours of their normally 
scheduled dosing time, then they should 
take their daily dose of study drug and 
then resume normal schedule. 
If the patient remembers they missed a 
dose within 12 hours of their normally 
scheduled dosing time, then they should 
take their daily dose of study drug and 
then resume normal schedule. 
Supplied 
Tablets, 42-count in child-resistant blister 
packaged cards and labeled per country 
requirement. 
Tablets, 42-count in child-resistant blister 
packaged cards and labeled per country 
requirement. 
Storage 
Store as follows:  
• In a secure location. 
• At 20°C–25°C (68°F–77°F), excursions 
permitted to 15°C–30°C (59°F–86°F). 
• Out of sight and reach of children. 
Store as follows:  
• In a secure location. 
• At 20°C–25°C (68°F–77°F), excursions 
permitted to 15°C–30°C (59°F–86°F). 
• Out of sight and reach of children. 
Procedures for inventory, reconciliation, and destruction or return of study tablets are provided in Section 11.5. 
a. Participants who participate in the PK substudy must take their medication in the morning. 
 


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5.2 
Safety Assessments 
5.2.1 Monitoring of Liver Injury 
Any patient experiencing signs and symptoms consistent with liver injury, such as a combination 
of nausea, vomiting, anorexia, fatigue, and/or right upper quadrant abdominal pain or discomfort, 
should undergo immediate testing prior to their next scheduled visit for ALT, AST, GGT, total 
and direct bilirubin, alkaline phosphatase, prothrombin time (PT), and international normalized 
ratio (INR). Should the patient have laboratory evaluations consistent with suspected liver injury, 
actions as outlined in Table 2 should be taken.  
5.2.2 Excessive GR/MR Antagonism  
Based on the mechanism of action of miricorilant, there is a theoretical risk of excessive GR 
antagonism and excessive MR antagonism. Excessive GR antagonism could manifest with 
findings such as weakness, tiredness, dizziness, orthostatic hypotension, hypoglycemia, 
dehydration, nausea, vomiting, diarrhea, and muscle aches. Excessive MR antagonism could 
manifest as hyperkalemia, dehydration, and hypotension; hypotension may be seen in the 
absence of antihypertensive medication. These symptoms should be monitored throughout the 
duration of the clinical trial both during treatment period (including Baseline) and in the follow-
up period. If excessive GR and MR antagonism is suspected, patients should discontinue the 
study medication, and administration of intravenous fluids (IVF), and intravenous (IV) or oral 
hydrocortisone begun without delay and the actions outlined in Table 2 should be taken. The 
half-life of miricorilant is approximately 21 to 23 hours. Symptoms should continue to be 
monitored even after the last dose of study medication in the follow-up period. 
5.3 
Dose Adjustment Criteria 
5.3.1 Dose Reduction 
No dose modification will be allowed. 
5.3.2 Dose Interruption and/or Discontinuation: General Criteria 
All attempts should be made to continue patients on the study for the duration of the study. 
However, study treatment can be temporarily interrupted up to 5 days if deemed necessary by the 
Investigator. Upon interrupting the study treatment, the Investigator should consult the Corcept 
Medical Monitor. Before restarting study treatment, the Investigator must obtain approval from 
the Corcept Medical Monitor. If the event that necessitated treatment interruption recurs after 
study treatment is restarted, the patient should be permanently discontinued from study 
treatment. In addition, patients will be permanently discontinued from study treatment if they 
experience any of the criteria listed for stopping treatment in Table 2. 
5.3.3 Dose Interruption and/or Discontinuation: Special Safety Events 
Guidelines for temporarily interrupting and restarting and for permanently discontinuing study 
treatment due to safety events (excessive GR or MR antagonism; hyperkalemia; hypotension; 
suspected liver injury; or significant trauma, surgery, or medical illness) are outlined in Table 2. 


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Table 2 
Criteria for Dose Modification or Discontinuation Due to Special Safety Events 
Safety Event 
Criteria for Interrupting and Restarting Study Treatment and Patient 
Management 
Criteria for Stopping Study Treatment 
Excessive GR or MR 
antagonism 
Criteria: signs and symptoms of excessive GR and MR antagonism (Section 1.5) 
Management:  
• Immediately interrupt miricorilant treatment for ≥5 days and start standard 
supportive care, including IV fluids, as indicated. 
• If appropriate, administer supplemental glucocorticoids given in high doses to 
overcome the GR antagonism produced by miricorilant. Initially, consider 
parenteral hydrocortisone, followed by additional IV or oral doses once or 
twice daily for 1 to 3 days and tapered thereafter, depending on clinical 
response. In some cases, higher doses of hydrocortisone for longer periods of 
time may be required. 
• If the patient has been receiving treatment with a MR antagonist, consider 
discontinuing it, particularly in the presence of hypotension. 
• Restart miricorilant treatment only if the workup reveals an alternative cause 
for symptoms of possible excessive GR/MR antagonism and after consultation 
with the Corcept Medical Monitor. 
A combination of the following Grade 3 or 
higher events:  
fatigue, anorexia, nausea, and vomiting 
(associated with decreased oral intake), 
and abdominal pain. 
Hypotension 
Criteria: development of hypotension while on study treatment. 
Management: 
• Confirm the diagnosis by in-office BP monitoring and orthostatic BP 
measurements. 
• Examine patient and check potassium levels.  
• If appropriate, advise the patient to hydrate orally with electrolyte containing 
hydration (e.g., Gatorade or Pedialyte). Hypotension can also be support with 
IV hydration with isotonic fluids. 
• Patients who have hypotension should have any antihypertensive medications 
and diuretic medications discontinued as appropriate.  
• Interrupt miricorilant if SBP <100 mm Hg or if DBP <60 mm Hg or if 
orthostatic hypotension is present or if patient requires treatment with 
IV fluids. 
SBP <100 mm Hg or DBP <60 mm Hg (as 
confirmed by in-office BP measurements) 
or orthostasis, despite the discontinuation 
of antihypertensive medications and IV 
and oral hydration. 


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Safety Event 
Criteria for Interrupting and Restarting Study Treatment and Patient 
Management 
Criteria for Stopping Study Treatment 
• Restart miricorilant only if hypotension is transient and reversible and not 
related to study medication, and after consultation with the Corcept 
Medical Monitor. 
Hyperkalemia 
Criteria: development of hyperkalemia during the study,  
Management:  
• Verify hyperkalemia and normal renal function. 
• Obtain ECG for evaluation of hyperkalemia. 
• Interrupt miricorilant if hyperkalemia is severe (>6.0 mEq/L) or if renal 
function is impaired. 
• As medically indicated, initiate treatment for hyperkalemia. 
• Restart miricorilant only if the underlying cause of hyperkalemia is transient 
and correctable and after discussion with the Corcept Medical Monitor. 
Severe (>6.0 mEq/L) hyperkalemia  
Confirmed ECG abnormalities including 
peaked T waves, shortened QT interval, 
ST segment depression, prolonged PR 
interval, flattened p wave, widened QRS, 
amplified R wave, or intraventricular/ 
fascicular/bundle branch blocks.  
Underlying renal disease.  
Suspected liver injury 
Criteria: AST or ALT >3 × ULN or total bilirubin >2.0 × ULN while on 
study drug  
Management: 
• Repeat liver biochemistries (ALT, AST, alkaline phosphatase, total bilirubin) 
within 48 to 72 hours of results.  
• Obtain a more detailed history of symptoms and prior or concurrent disease 
and a history of concomitant drug use (including nonprescription medication 
and herbal and dietary supplement preparations). 
• Obtain a history of exposure to environment chemical agents. 
• Rule out other causes of liver disease.  
• Obtain additional tests to evaluate liver function, as appropriate (e.g., INR, 
direct bilirubin). 
• Continue to monitor the liver biochemistry two or three times weekly but no 
less frequently than once weekly. Frequency can decrease to once a week or 
less if abnormalities stabilize, or study drug has been discontinued and the 
patient is asymptomatic. 
• Consider a gastroenterology or hepatology consultation. 
Study drug will be stopped if:  
• ALT or AST >5 × ULN.  
• ALT or AST >3 × ULN and 
(TBL >2 × ULN or INR >1.5).  
• ALT or AST >3 × ULN with the 
appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, 
fever, rash, and/or eosinophilia (>5%). 


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Safety Event 
Criteria for Interrupting and Restarting Study Treatment and Patient 
Management 
Criteria for Stopping Study Treatment 
• During the period of close observation, study drug can be continued if desired 
at the discretion of Corcept Medical Monitor and Investigator unless one of the 
criteria for stopping study treatment are met. 
Significant trauma, surgery, 
or medical illness at any 
time during the study 
(through 2 weeks after last 
dose) 
Management: 
• As medically indicated, interrupt miricorilant treatment and provide 
supplemental hydrocortisone to offset the GR antagonism even in patients not 
experiencing signs and symptoms of excessive antagonism.  
• After resolution of the physiological stress associated with the event and if still 
within the Treatment Period, resume miricorilant. 
Patient does not recover from the 
significant trauma, surgery, or medical 
illness within the Treatment Period. 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; DBP, diastolic blood pressure; ECG, electrocardiogram; 
GR, glucocorticoid receptor; INR, international normalized ratio; IV, intravenous; MR, mineralocorticoid receptor; SBP, systolic blood pressure; 
TBL, total bilirubin level; ULN, upper limit of normal. 


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5.4 
Concomitant Medications 
Miricorilant is primarily eliminated hepatically by CYP2C19 and exhibits inhibitory potential of 
CYP3A4, CYP2C8, CYP2C9, UGT1A1, and BCRP in vitro (Section 1.2.2). Concomitant 
medications that have overlapping enzyme/transporter pathways with miricorilant must be 
evaluated for potentially clinically relevant drug-drug interactions. Accordingly, the 
coadministration of concomitant medications in this study is at the discretion of the Principal 
Investigator and/or Corcept Medical Monitor.  
5.4.1 Permitted Concomitant Medications 
Medications required to treat AEs, manage symptoms, concurrent diseases, and supportive care 
agents, such as pain medications, anti-emetics, and antidiarrheal agents, are allowed at the 
discretion of the Principal Investigator and/or Corcept Medical Monitor. Patients must be 
instructed to notify the investigational site about any new medications they take after the start of 
study treatment. All medications (other than study treatments) administered 30 days before study 
entry (i.e., after a patient signs the ICF) and during the study must be listed on the concomitant 
medications eCRF. 
Permitted concomitant medications are listed in Table 3. 
Table 3 
Permitted Concomitant Medications 
Medication 
Use and/or Restriction 
Antipsychotic medication 
No change to the antipsychotic medication during the study duration 
through the Follow-Up Visit 
Insulin and oral antidiabetic 
medication 
Dose may be decreased or stopped during study treatment to prevent 
hypoglycemia. Do not add new antidiabetic medication or titrate existing 
medication up without prior consultation with the Corcept Medical 
Monitor. 
Antihypertensive medication 
Dose may be decreased or stopped during study treatment to prevent 
hypotension or orthostatic symptoms. Do not increase dose or add new 
antihypertensive medications without prior consultation with the Corcept 
Medical Monitor. 
Lipid-lowering drug 
No increases in current dose allowed from 4 weeks before Baseline 
through the Follow-up Visit. 
Antidepressant medication 
No restrictions unless there is a potential DDI. 
Anxiolytic medication such as 
benzodiazepines 
No restrictions unless there is a potential DDI. 
 
5.4.2 Permitted Concomitant Therapy Requiring Caution 
Permitted concomitant medications to be used with caution from 1 week before Baseline through 
the Follow-up Visit are as follows:  
• Moderate inhibitors or inducers of CYP2C19. 


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• Substrates metabolized predominantly by CYP3A4, CYP2C8, and/or CYP2C9 with a 
narrow therapeutic index. 
• Strong inhibitors of CYP3A4, CYP2C8, and/or CYP2C9. 
• Medications that carry a possible risk for QT prolongation. 
5.4.3 Prohibited Medications 
The following medications are prohibited during treatment with miricorilant in this study: 
• Antipsychotic medication clozapine. 
• Mood stabilizing medication carbamazepine. 
• Other investigational therapies. 
• Digoxin or other medications with increased risk for toxicity in the event of electrolyte 
changes. 
• Prescription or over-the-counter medications that are strong inducers or strong inhibitors 
of CYP2C19 are prohibited.  
• Systemic corticosteroids, including inhaled corticosteroids (with exception of temporary 
use for treatment of excessive GR antagonism), potent (group III) topical corticosteroids, 
and intra-articular corticosteroids 
• Prescription or over-the-counter weight-loss treatments, including but not limited to: 
– Olanzapine/samidorphan (Lybalvi) or other samidorphan drug combinations. 
– Prescription drugs such as orlistat (Xenical), phentermine (Adipex-P, Pro-Fast SA, 
Pro-Fast SR, Fastin, Oby trim, Zantryl, Teramine, Phentride, Phentercot, Obephen, 
Oby-cap), phentermine/topiramate (Qsymia), liraglutide (Saxenda), semaglutide 
(Wegovy), or naltrexone HCl/bupropion HCl (Contrave). 
– Over-the-counter anti-obesity agents such as orlistat (Alli), herbal supplements, or 
other alternative remedies such as Cortislim, Dexatrim, Acutrim. 
5.5 
Method of Treatment Assignment and Randomization 
All patients will be centrally randomized to study treatment using an interactive web response 
system (IWRS). Permuted block randomization will be used to ensure approximate balance 
among treatment groups. Before the study is initiated, the log-in information and directions for 
the IWRS will be provided to each site. 
Study treatment will be dispensed at the study visits summarized in the Schedule of Assessments 
(SoA) (Appendix A).  
Returned study treatment should not be re-dispensed to patients. However, study treatment 
brought back by the patient for accounting reasons can be returned to the patient. 
5.6 
Blinding 
This is a double-blind, placebo-controlled study. Tablets containing 100 mg miricorilant or 
placebo will be identical in appearance. 
The Sponsor or designee, the Investigator, the Corcept Medical Monitor, study-site personnel, 
and the patient will be blinded to the study drug and will not be allowed to view the results of 


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laboratory tests that have the potential to reveal a patient’s treatment arm due to the expected 
effect of the active treatment on the analyte involved. 
The IWRS will be programmed with blind-breaking instructions. The blind may be broken if, in 
the opinion of the Investigator, it is in the patient’s best interest for the Investigator to know the 
study treatment assignment. To maintain the overall quality and legitimacy of the clinical trial, 
unblinding should occur in exceptional circumstances. These circumstances could include but are 
not limited to pregnancy of the patient or pregnancy of the patient’s partner. Corcept must be 
notified before the blind is broken unless identification of the study treatment is required for a 
medical emergency in which the knowledge of the specific blinded study treatment will affect 
the immediate management of the patient’s condition (e.g., antidote available). In this case, 
Corcept must be notified within 24 hours after breaking the blind. The date and reason that the 
blind was broken must be recorded in the source documentation and eCRF, as applicable. 
5.7 
Dose Diary 
A dose diary will be provided, and patients will be instructed to bring their dose diary to each 
clinic visit. Patients should complete an entry in the diary for each self-administered dose of 
miricorilant. Entries will include the number of tablets and the date and time of miricorilant 
administration. Time and dose administered should be documented in the clinic charts. 
5.8 
Product Accountability and Treatment Adherence  
Patients will be instructed to return all unused study tablets when they come in for each clinic 
visit. Study treatment adherence will be determined by review of the dose diary (Section 5.7) and 
counting returned tablets. On visit days, study treatment should be taken in the clinic during the 
visit and after initial blood draws.  
A patient who is assigned a study treatment (i.e., 600 mg miricorilant or placebo) will be 
considered nonadherent if he or she misses >30% of the prescribed doses during the study, unless 
the patient’s study treatment was withheld by the Investigator for safety reasons. Similarly, a 
patient will be considered nonadherent if he or she is judged by the Investigator to have 
intentionally or repeatedly taken more than the prescribed amount of study treatment. Patients 
found to be nonadherent with their assigned treatment regimen should be assessed to determine 
the reason for nonadherence and educated and/or managed as deemed appropriate by the 
Investigator to improve adherence. 
5.9 
Independent Data Monitoring Committee to Monitor Patient Safety  
An Independent Data Monitoring Committee (IDMC) will be established to conduct periodic 
reviews of data to ensure the safety of patients. The IDMC will be composed of at least 4 voting 
members: three physicians and one statistician, who, collectively, have endocrinology, 
psychiatry, and hepatology experience in the treatment of patients with schizophrenia or bipolar 
disorder and in the conduct and monitoring of randomized clinical trials. The IDMC will meet at 
least quarterly. Further details describing the IDMC composition, contents of data reports, 
responsibilities, and decision rules will be described in the IDMC Charter. 


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6 
DESCRIPTION OF STUDY ASSESSMENTS AND PROCEDURES AND 
APPROPRIATENESS OF MEASUREMENTS 
Study procedures and their timing are summarized in the SoA (Appendix A). Protocol waivers or 
exemptions are not allowed. 
The Investigator and Sponsor will conduct the study in accordance with International Council on 
Harmonisation (ICH) Good Clinical Practice (GCP) and local regulations. Adherence to the 
study design requirements, including those specified in the SoA, is essential and required for 
study conduct, and the Investigator must ensure that trial procedures are performed as described 
in the protocol. During the study, procedures and observations will be monitored to confirm that 
study requirements are being followed as outlined in the SoA. 
In the event that a patient is unable to come to the clinic to participate in study-related visits or 
procedures, sponsor-approved alternative options may be provided to the Investigator sites based 
on the needs and safety of patients. This may include the provision of study-drug dispensation 
and delivery outside of a clinic visit. 
6.1 
Informed Consent and Screening 
Written informed consent must be obtained before initiating any study-mandated procedures.  
All screening evaluations must be completed and reviewed to confirm that potential patients 
meet all eligibility criteria. The Investigator will maintain a screening log to record details of all 
patients screened and to confirm eligibility or record reasons for screening failure, as applicable.  
Procedures conducted as part of the patient’s routine clinical management (e.g., blood count) and 
obtained before signing of the informed consent form (ICF) may be used for Screening or 
Baseline purposes, provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA (Appendix A). 
6.2 
Placebo Tablet Swallow Assessment 
Patients will be asked to swallow 6 placebo tablets during screening to ensure ability to 
participate in the study. These placebo tablets will be administered with 8 oz (240 mL) of water 
and may be taken with or without food. 
6.3 
History 
Medical history, including details regarding surgeries, illnesses and allergies, date(s) of onset, 
and whether conditions are currently ongoing, and medication history will be collected on all 
patients during Screening. Medical history will be updated at the Day 1 Visit and will then serve 
as the baseline for other clinical assessments. 
6.4 
Safety Measures 
Safety will be determined from evaluation of AEs, physical examinations, clinical laboratory 
tests, vital signs, and ECGs. 


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6.4.1 Physical Examination and Vital Signs  
Physical examinations including a basic neurologic examination will be performed at every visit 
during the study and at Follow-Up. 
Vital signs will be measured at every visit during the study and include resting heart rate, blood 
pressure, respiratory rate, and body temperature. Systolic and diastolic blood pressure, measured 
in mm Hg, will be measured after patients have been at rest (seated) for ≥3 minutes. Heart rate, 
measured in beats per minute, will be taken after the patient has been in a resting state (seated) 
for ≥3 minutes. The heart rate should be recorded over 30 seconds or longer. 
Orthostatic vital signs should be performed for all patients at every visit. Heart rate and blood 
pressure should be taken first in a supine state at rest (lying for ≥3 minutes). Patient should then 
be instructed to stand and heart rate and blood pressure should be repeated 3 minutes after the 
patient has stood. 
Unscheduled assessments of vital signs can be performed as necessary.  
6.4.2 Height  
Height will be measured once, at Screening. 
6.4.3 Electrocardiogram 
Twelve-lead ECG tracings will be obtained in triplicate from all patients at every visit during 
the study. Patients should be lying down resting for approximately 15 minutes before each ECG 
evaluation. It is acceptable to start taking ECG 1-minute prior. A central reviewer will be used; 
instruction will be provided in the imaging manual.  
The Investigator or designee will indicate on the site’s copy whether the ECG was normal, 
abnormal but not clinically significant, or abnormal and clinically significant. Any new or 
worsened abnormality noted as clinically significant will be reported as an AE. 
6.4.4 Adverse Events 
Details on definitions and reporting of AEs are provided in Section 8. 
All AEs will be recorded from the time of signing the ICF until 28 days after the last dose of 
study treatment. Patients should be monitored for AEs and AEs assessed for expectedness 
consistent with the current IB for miricorilant. To help characterize any possible relationships 
between drug exposure and the clinical event, when an SAE occurs, ACTH and cortisol should 
be assessed as close to the time of the event as possible, and a PK sample may be drawn at the 
discretion of the Investigator. 
6.4.5 Clinical Laboratory Assessments 
6.4.5.1 
Laboratory Parameters 
Blood samples will be collected for the analysis of safety in all patients at the times indicated in 
the SoA (Appendix A). Laboratory samples will be analyzed at central or local laboratories as 
appropriate. 


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Laboratory values for an analyte that are outside of the normal range per the central or local 
laboratory will be identified and should be assessed as clinically significant or not and repeated 
at the Investigator’s discretion. The CTCAE grading for severity of abnormal labs should be 
applied for consistency in the evaluation and grading assessment.  
The Investigator will review all laboratory reports, evaluate the results, and sign/date the report. 
Laboratory tests to be performed are listed in Table 4 and should be performed according to the 
schedule provided in the SoA (Appendix A). 
Table 4 
Clinical Laboratory Variables Evaluated During the Study 
Hematology 
Serum Chemistry 
Urinalysis 
Red blood cell count  
Hemoglobin  
Hematocrit  
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin volume 
Mean corpuscular volume  
Platelet count 
Mean platelet volume 
Red blood cell distribution width 
White blood cell count 
 
White blood cell count with 5-part 
differential 
Neutrophils (percent and absolute) 
Lymphocytes (percent and absolute) 
Monocytes (percent and absolute) 
Eosinophils (percent and absolute) 
Basophils (percent and absolute) 
Sodium  
Potassium  
Calcium  
Chloride  
Phosphorus  
Magnesium  
Creatinine 
Bilirubin (total and direct) 
Albumin  
Alkaline phosphatase 
Lactate dehydrogenase 
Aspartate aminotransferase  
Alanine aminotransferase 
Glucose (fasting)  
Blood urea nitrogen 
Uric acid  
Bicarbonate  
Total protein  
Gamma-glutamyl transferase 
Drug screen 
Pharmacokinetics 
Miricorilant and its metabolites 
Pregnancy 
Serum/urine pregnancy test (for 
women of childbearing potential) 
Thyroid Function 
Thyroid-stimulating hormone  
Free thyroxine (T4) 
Lipid Panel 
Hormones 
Ad Hoc Testing 
Total cholesterol 
Direct Low-density lipoprotein-
cholesterol-c 
High-density lipoprotein-cholesterol 
Very low-density lipoprotein 
cholesterol 
Triglycerides (fasting only) 
Follicle-stimulating hormone  
Hypothalamic-pituitary-adrenal 
(HPA)-axis parameters: 
Plasma adrenocorticotropic 
hormone (ACTH) (morning) 
Serum cortisol (morning) 
Prothrombin time 
(PT)/international normalized 
ratio (INR) 
Activated partial thromboplastin 
time (aPTT) 
Creatine kinase 
Virus screen (hepatitis A, B, and 
C viruses) 
Antinuclear antibodies (ANA) 
Anti-smooth muscle antibodies 
(ASMA)  
Anti-liver-kidney microsome 
(anti-LKM) 
Glycemic Parameters 
Glycated hemoglobin (HbA1c) 
Serum insulin (fasting) 
Plasma glucose (fasting) 
Note: See Appendix A for the laboratory test schedule; ad hoc testing will be performed at the discretion of the 
Corcept Medical Monitor (hepatitis B and hepatitis C testing will be performed at Screening as listed in 
Appendix A and may also be performed on an ad hoc basis as needed). 
 


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6.4.5.2 
Sample Collection, Preparation, and Shipping 
Instructions for collection, preparation, and shipping of all laboratory samples will be provided 
in the study laboratory manual. Long-term retention of biological samples is described in 
Section 11.4. 
6.4.5.3 
Blood Volume Summary 
Blood samples will be taken for analysis of safety laboratory, efficacy, and PK parameters, at the 
time points indicated in the SoA (Appendix A). The total volume of blood to be collected from 
each patient will be specified in the ICF. 
6.5 
Efficacy Assessments 
The key primary efficacy assessment in this study is body weight measurement. The secondary 
efficacy measurement is waist-to-hip ratio. 
Body weight will be measured at every visit. Body weight will be measured without overcoat 
and shoes and with only light clothing.  
Waist circumference will be measured for all patients at every visit. Clinical sites will be 
provided with tape measures to ensure consistency of circumference measurements. Waist 
circumference should be measured midway between the lower rib margin and iliac crest. Hip 
circumference should be measured at the level of the widest circumference over the greater 
trochanters. Detailed instructions for measurements of the waist and hip circumferences will be 
provided in the study manual. 
The waist-to-hip ratio will be calculated as the ratio of the circumference of the waist to the hip. 
6.6 
Pharmacokinetic Assessments 
Blood samples will be collected for measurement of plasma concentrations of miricorilant and its 
relevant metabolites as specified in the SoA (Appendix A). Instructions for the collection and 
handling of biological samples will be provided in the study manual. The actual date and time 
(24-hour clock time) of each sample will be recorded. 
Samples collected for analyses of miricorilant plasma concentration may also be used to 
evaluate safety or efficacy aspects related to concerns arising during or after the study. Refer 
to Section 9.4.6 for a description of variables to be analyzed. 
Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
6.7 
Pharmacodynamic/Biomarker Assessments 
The development and improvement of therapies increasingly depends on insights gained from 
analysis of biomolecules. During this study and with the consent of patients (see Section 10.3.1), 
biological samples (e.g., blood, plasma, serum, or tumor tissue) will be obtained, some for 
analysis during the study and others for future analysis of genes or proteins at the time points 
specified in Appendix A. These samples will be used to develop a better understanding of the 
mechanisms of both treatment response (predictive biomarkers) and disease processes 


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(prognostic biomarkers) and ultimately to identify which patients have a high probability to 
benefit from treatment with miricorilant and which do not. 
6.8 
Clinician Assessed Outcomes 
The clinician assessed outcome assessments in the study include the BPRS, C-SSRS, and CGI. 
A brief description of each is provided below. 
The BPRS is a scale used to track changes in schizophrenia symptoms over time. The scale 
involves an interview of the patient by the Investigator and includes 24 different symptom areas 
in which the Investigator ranks the severity of each symptom using a scale of 1 (symptom is 
absent) to 7 (symptom is severe). 
The C-SSRS is a suicidal ideation rating scale used to evaluate suicidality (Posner et al. 2011). 
The C-SSRS consists of a series of questions to patients that can help identify patients at risk for 
suicide, assess the severity and immediacy of that risk, and gauge the level of support the patient 
may need. 
The CGI is a scale used to assess the patient’s global functioning. The CGI has 2 components—
the CGI-Severity (CGI-S), which rates illness severity, and the CGI-Improvement (CGI-I), 
which rates change from the initiation (baseline) of treatment. The CGI-S asks the Investigator 
one question: “Considering your total clinical experience with this particular population, how 
mentally ill is the patient at this time?”, which is rated on the following 7-point scale: 1=normal, 
not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely 
ill; 7=among the most extremely ill patients. The CGI-I also asks the Investigator 1 question: 
“Compared to the patient's condition at Baseline, this patient’s condition is: 1=very much 
improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no 
change from Baseline (the initiation of treatment); 5=minimally worse; 6=much worse; 7=very 
much worse since the initiation of treatment. Both ratings are based on observed and reported 
symptoms. 
The MADRS-SIGMA is a ten-item diagnostic questionnaire used by psychiatrists to measure the 
severity of depressive episodes in patients with mood disorders. The questionnaire includes 
questions on the following symptoms: 1) Apparent sadness, 2) Reported sadness, 3) Inner 
tension, 4) Reduced sleep, 5) Reduced appetite, 6) Concentration difficulties, 7) Lassitude, 
8) Inability to feel 9) Pessimistic thoughts, and 10) Suicidal thoughts. Each question yields a 
score from 0–6; higher MADRS-SIGMA score indicates more severe depression. 
The YMRS is a clinical interview scale to assess the severity of manic states. The scale has 
eleven items and is based on the patient’s subjective report of his or her clinical condition. The 
purpose of each item is to rate the severity of that abnormality in the patient, making it useful for 
continuous evaluations of manic symptoms. It can help guide clinicians on treatment planning 
and progress. 
6.9 
Appropriateness of the Measures 
All efficacy and safety measurements are well-validated and the standard measurements in this 
patient population are appropriate for this study. 


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7 
STUDY ASSESSMENTS AND PROCEDURES BY STUDY VISIT 
The schedule of assessments is provided in Appendix A. 
Corcept will be promptly notified of any protocol deviations.  
The acceptable visit window for all visits during the Treatment Period is ±2 days and the 
acceptable visit window for the Follow-up Period is ±5 days. 
7.1 
Screening Period (Day-28 to Day-1) 
At the start of Screening, the study will be discussed with the patient, and a patient wishing to 
participate must give written consent prior to any study-related procedures or change in 
treatment. The patient must also give written authorization regarding privacy requirements prior 
to any study-related procedures or change in treatment. 
After informed consent is obtained, prospective patients will be evaluated for entry into the study 
according to inclusion and exclusion criteria (Section 4.1 and 4.2). Each patient who receives 
study treatment will be assigned a patient number that will be used on patient documentation 
throughout the study. 
The patient should be instructed to fast (no food or drink other than water) before this clinic visit 
(at least 8 hours). 
The following Screening procedures will be performed: 
• Record medical history 
• In patients with schizophrenia, conduct MINI  
• In patients with bipolar disorder, conduct DSM-5 diagnostic assessment 
• Record prior and concomitant medications 
• Record demographic information 
• Perform urine drug test 
• Perform placebo tablet swallow assessment 
• Measure height and body weight 
• Measure waist-to-hip ratio 
• Perform physical examination 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Conduct psychological assessments:  
– In patients with schizophrenia: C-SSRS, CGI, and BPRS 
– In patients with bipolar disorder: C-SSRS, CGI, YMRS, and MADRS-SIGMA 
• Perform laboratory tests: 
– Hematology with platelet and white blood cell count (WBC) differential 
– Chemistry panel (fasting) 
– Lipid panel (fasting) 
– HbA1c 
– Serum pregnancy test (women of child-bearing potential) 


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– FSH test (only for women who have medically confirmed ovarian failure or are 
postmenopausal) 
– Hepatitis B screening  
– Hepatitis C screening 
– Thyroid-stimulating hormone (TSH) 
– Free thyroxine (T4) 
7.2 
Baseline (Day 1) 
The patient should be instructed to fast (no food or drink other than water) before this clinic visit 
(at least 8 hours). The following procedures will be performed for the baseline assessment at 
Day 1: 
• Confirm informed consent was obtained 
• Confirm patient eligibility (see Section 4.1 and 4.2 for inclusion and exclusion criteria) 
• Confirm medical and medication history  
• Record concomitant medications 
• Perform urine drug test 
• Measure body weight 
• Measure waist-to-hip ratio 
• Perform physical examination 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) before dosing and 2 hr ±15 min after dosing 
• Perform laboratory tests: 
– Hematology with platelet and WBC differential 
– Chemistry panel (fasting) 
– Lipid panel (fasting) 
– HbA1c  
– ACTH (morning–8 AM) 
– Serum insulin (fasting) 
– Plasma glucose (fasting) 
– Serum cortisol (morning–8 AM) 
– TSH 
– T4 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
• Conduct psychological assessments:  
– In patients with schizophrenia: C-SSRS, CGI, and BPRS 
– In patients with bipolar disorder: C-SSRS, CGI, YMRS, and MADRS-SIGMA 
• Glucocorticoid receptor activity marker 
• Provide dietary and exercise counseling 
• Record any AEs 
• Perform study randomization 


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• Dispense study tablets; patient will take their first dose of study treatment in the clinic at 
this visit after clinic assessments 
• Provide the patient with dose diary 
7.3 
Treatment Period 
At all clinic visits during the Treatment Period, the following will be performed: 
• Record any AEs 
• Record concomitant medications 
• Perform urine pregnancy test (women of child-bearing potential); if urine pregnancy test 
is positive, the result should be confirmed with a serum pregnancy test 
• Perform physical examination 
• Measure body weight 
• Record waist-to-hip ratio 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Conduct psychological assessments:  
– In patients with schizophrenia: C-SSRS, CGI, and BPRS 
– In patients with bipolar disorder: C-SSRS, CGI, YMRS, and MADRS-SIGMA 
In addition, assessments will be performed at specific visits of the Treatment Period as indicated 
in the following sections. 
7.3.1 Week 1: Study Day 8 (±2 Days) 
• Perform assessments listed in Section 7.3 
• Dispense study tablets 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
• Record unused study tablets brought back by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 
7.3.2 Week 2: Study Day 15 (±2 Days) 
• Perform assessments listed in Section 7.3 
• Dispense study tablets 
• Perform laboratory tests: 
– Chemistry panel 
• Record unused study tablets brought back by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 


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7.3.3 Week 4: Study Day 29 (±2 Days) 
• Perform assessments listed in Section 7.3 
• Dispense study tablets 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
– Lipid panel  
– ACTH (morning–8 AM) 
– Serum cortisol (morning–8 AM) 
• Record unused study tablets brought back by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 
For patients who consent to participate in the PK substudy only: 
Patients in the PK substudy will be required to take their dose of study treatment both the day 
prior and the day of their Week 4 visit in the clinic (witnessed dosing). Blood samples will be 
collected at the time points specified in the PK plan outlined in the study manual. 
7.3.4 Week 6: Study Day 43 (±2 Days) 
• Perform assessments listed in Section 7.3 
• Dispense study tablets 
• Perform laboratory tests: 
– Chemistry panel  
• Record unused study tablets brought back by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 
• Provide a refresher on dietary and exercise counseling on weight loss 
7.3.5 Week 8: Study Day 57 (±2 Days) 
• Perform assessments listed in Section 7.3 
• Dispense study tablets 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
– Lipid panel  
• Record unused study tablets brought back by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 
7.3.6 Week 10: Study Day 71 (±2 Days) 
• Perform assessments listed in Section 7.3 
• Dispense study tablets 


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• Perform laboratory tests: 
– Chemistry panel  
• Record unused study tablets brought back by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 
7.3.7 Week 12: Study Day 85 (±2 Days) 
Patients should be instructed to fast before this clinic visit (i.e., no food or drink other than water 
for at least 8 hours).  
• Perform assessments listed in Section 7.3 
• Perform laboratory tests: 
– Chemistry panel (fasting) 
– Hematology with platelet and WBC differential 
– Lipid panel (fasting) 
– Serum insulin (fasting) 
– Plasma glucose (fasting) 
– ACTH (morning–8 AM) 
– Serum cortisol (morning–8 AM) 
– TSH 
– Free T4 
– HbA1c 
• Record unused study tablets returned by the patient 
• Evaluate study treatment adherence based on returned dose diary and counting unused 
study tablets 
• Glucocorticoid receptor activity marker 
7.4 
Early Termination Visit (In-Clinic Visit)  
Patients who discontinue the study drug before the end of the Treatment Period (12 weeks) will 
be asked to complete an ET visit at the time of the last dose of study drug (or soon thereafter). 
They should be instructed to fast before coming to the ET clinic visit (i.e., no food or drink other 
than water for at least 8 hours).  
The following assessments should be performed during the ET visit: 
• Record any AEs 
• Record concomitant medications 
• Record unused study tablets returned by the patient 
• Evaluate study treatment adherence based on dose diary and pill counting 
• Perform physical examination 
• Measure body weight 
• Record waist-to-hip ratio 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 


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• Perform laboratory tests: 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
– Hematology with platelet and WBC differential 
– Chemistry panel (fasting) 
– Lipid panel (fasting) 
– HbA1c 
– Serum insulin (fasting) 
– Plasma glucose (fasting) 
– TSH 
– Free T4 
– ACTH (morning–8 AM) 
– Serum cortisol (morning–8 AM) 
• Conduct psychological assessments:  
– In patients with schizophrenia: C-SSRS, CGI, and BPRS 
– In patients with bipolar disorder: C-SSRS, CGI, YMRS, and MADRS-SIGMA 
• Glucocorticoid receptor activity marker 
7.5 
Follow-Up Visit (In-Clinic Visit; 28±5 Days after Last Dose of Study Drug) 
For patients who complete 12 weeks of treatment or for patients who discontinue early from the 
study drug, the Follow-Up visit will be conducted 28±5 days after their last dose of study drug. 
The following assessments should be performed during the end-of-study Follow-up visit: 
• Record any AEs 
• Record concomitant medications 
• Perform physical examination 
• Measure body weight 
• Record waist-to-hip ratio 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Perform laboratory tests: 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
– Hematology with platelet and WBC differential 
– Chemistry panel 
– Lipid panel 
• Conduct psychological assessments:  
– In patients with schizophrenia: C-SSRS, CGI, and BPRS 
– In patients with bipolar disorder: C-SSRS, CGI, YMRS, and MADRS-SIGMA 


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7.6 
Unscheduled Visits 
As appropriate, assessments deemed clinically necessary by the Investigator may be done at 
unscheduled visits. 


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8 
SAFETY EVENT DOCUMENTATION AND REPORTING 
8.1 
Investigator’s Responsibilities 
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for providing appropriate medical care. By exercising appropriate healthcare options, the 
Investigator remains responsible for managing AEs. Duration of follow-up and requirements for 
immediate SAE reporting (within 24 hours of the event) are described below. 
8.2 
Monitoring Safety Data During the Study 
Safety results collected during the study (e.g., AEs, laboratory test results, and physical 
findings) will be monitored on an ongoing basis by the Corcept Medical Monitor and 
Investigator. In addition, an IDMC will be established to conduct periodic reviews of data to 
ensure the safety of patients (Section 5.9). All abnormal lab, ECG, and exam findings will be 
assessed for clinical significance. The use of CTCAE severity grading will be implemented for 
systematically and consistently evaluating abnormal labs, ECG and vitals findings. All grade 3 
and above findings will immediately be reported to Corcept’s Medical Monitor within 24 hours.  
In addition, an IDMC will conduct periodic reviews of data to ensure the safety of patients (see 
Section 5.9). 
8.3 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a study patient administered a pharmaceutical 
product, which does not necessarily have to 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 that emerges or 
worsens relative to the patient’s pretreatment baseline, whether or not it is considered to be 
related to the investigational product. 
Illnesses present before the patient signs the ICF are considered pre-existing conditions and are 
documented on the medical history eCRF. Pre-existing conditions that worsen during the study 
are entered on the AE eCRF. 
8.4 
Definition of a Serious Adverse Event 
An SAE is any AE that meets any of the following criteria: 
• Results in death (i.e., the AE caused or led to the fatality). 
• Is life-threatening (i.e., the AE refers to an event in which the patient was at risk of death 
at the time of the event; it does not refer to an event that hypothetically might have 
caused death if it were more severe). 
• Requires hospitalization or prolongation of existing hospitalization (i.e., hospitalizations 
for scheduled treatments and elective medical/surgical procedures are not SAEs by this 
criterion). 
• Results in persistent or significant disability/incapacity (i.e., the AE results in substantial 
reduction of the patient’s ability to perform activities of daily living). 


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• Results in a congenital anomaly or birth defect (i.e., an adverse finding in a child or fetus 
of a patient exposed to the study medication before conception or during pregnancy). 
• Involves other medically important conditions (i.e., the AE does not meet any of the 
above serious criteria but based on appropriate medical judgment, may jeopardize the 
patient or require medical or surgical intervention to prevent one of the serious outcomes 
listed in these criteria). 
8.5 
Expectedness 
An SAE is considered unexpected if not reported in the IB or if the event is of greater severity or 
frequency than described in the IB. 
8.6 
Clinical Significance 
The Investigator (or medically qualified designee) is responsible for determining whether an AE 
is clinically significant for the patient. Clinical significance will be documented in the patient’s 
medical records with the AE information. 
8.7 
Clinical Laboratory Adverse Events 
All out-of-range laboratory values will be determined to be clinically significant or not clinically 
significant by the Investigator. An abnormal laboratory value that meets any of the following 
criteria will be recorded as an AE on the eCRF: 
• Leads to dose interruption or discontinuation or patient withdrawal from the study. 
• Is accompanied by clinical symptoms. 
• Requires a change in concomitant medications. 
Other clinically significant laboratory values should be reported as AEs at the discretion of the 
Investigator. 
Patients with a clinically significant out-of-range laboratory value will be followed until the 
laboratory value returns to normal, or the patient’s baseline value, or the value becomes 
medically stable, or the patient is deemed by the Investigator to be lost to follow-up. The 
Investigator will treat the patient as medically required at appropriate intervals until this occurs. 
The Investigator should report any Grade 3 or 4 laboratory abnormalities to Corcept. 
8.8 
Documentation of Adverse Events 
Patients will be evaluated and questioned to identify AEs during the study. 
Collection of AEs will start immediately following signing of the ICF and will continue 
throughout the study as noted in the SoA (Appendix A). Illnesses present before the patient signs 
the ICF are considered pre-existing conditions and are to be documented on the medical history 
eCRF. Pre-existing conditions that worsen during the study are entered on the AE eCRF. 
Adverse events that occur after start of study treatment after randomization to miricorilant or 
placebo and up to and including 28 days after administration of the last dose of miricorilant or 
placebo will be considered TEAEs.  
All AEs will be documented on the AE eCRF and in the patient’s medical record. The following 
attributes must be assigned: (1) description, (2) dates of onset and resolution, (3) severity (see 


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Section 8.9.1), (4) relationship to the study treatment (see Section 8.9.2), (5) seriousness criteria 
if applicable (see Section 8.4), and (6) action taken. The Investigator will actively solicit this 
information and assess the AEs in terms of severity and relationship to each study treatment. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
unifying diagnosis whenever possible, rather than individual underlying signs and symptoms. 
The Investigator will treat the patient as medically required until the AE either resolves or 
becomes medically stable. This treatment may extend beyond the duration of the study. The 
Investigator will record treatment and medications required for treatment on the appropriate 
eCRF(s). 
In the event that a patient is withdrawn from the study because of an AE, the event must be 
recorded on the Termination eCRF as the reason for discontinuation. 
All AEs considered to be related (see Section 8.9.2) to study treatment and all SAEs will be 
followed until resolved or until a stable status has been achieved. 
All SAEs that are study treatment-related and unexpected (not reported in the IB or if the event is 
of greater severity or frequency than that described in the IB) must be reported to the governing 
IRB as required by the IRB, local regulations, and the governing health authorities. 
8.9 
Adverse Event Classification 
8.9.1 Intensity Grades of Adverse Events 
The seriousness of an AE should not be confused with its severity. To describe the maximum 
severity of the AE on the AE eCRF, the Investigator will use the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0 (NCI 2017). For 
events not listed in the NCI-CTCAE, the definitions from the NCI-CTCAE provided in Table 5 
should be used to evaluate the grade of severity for the AE. 
Table 5 
Adverse Event Grades Based on the Common Terminology Criteria for 
Adverse Events 
Grade 
Description 
1 
Mild: asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated 
2 
Moderate: minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living (e.g., preparing meals, shopping for groceries or clothes, using 
the telephone, and managing money) 
3 
Severe: severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting selfcare activities of daily living (e.g., 
bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden) 
4 
Life-threatening: Life-threatening consequences; urgent intervention indicated 
5 
Death: Death related to AE 
Source: National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 
(NCI 2017). 


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8.9.2 Relationship of Adverse Event to Study Drug or Procedure 
The Investigator responsible for the patient’s care (or qualified designee) will assess causality of 
AEs and SAEs based on the causal attribution guidance in Table 6. The Investigator’s 
assessment of causality must be provided for all AEs (serious and nonserious). 
Table 6 
Causal Attribution Guidance for Adverse Events 
Not related to study treatment  
An AE that is judged to be clearly due only to extraneous causes such as 
diseases, environment, and the like or for which it is temporally 
implausible to be related to use of the study treatment. The cause must be 
noted on the AE eCRF. 
Possibly related to study treatment 
An AE that might be due to the use of the study treatment. The relationship 
in time is reasonable; therefore, a causal relationship cannot be excluded. 
An alternative explanation is inconclusive, e.g., concomitant drug (s), 
concurrent disease (s). 
Probably related to study treatment 
An AE that might be due to the use of the study treatment. The relationship 
in time is suggestive. An alternative explanation is less likely, e.g., 
concomitant drug(s) or concurrent disease(s). 
8.10 
Procedures for Reporting a Serious Adverse Event 
Any SAE occurring from the time of informed consent and for ≤28 days after the last dose of 
study treatment must be reported within 24 hours to the Corcept Medical Monitor and recorded 
on the SAE Form. All patients with an SAE must be followed and the outcomes reported. The 
Investigator must supply Corcept and the IRB with any additional requested information (e.g., 
autopsy reports and terminal medical reports). 
8.11 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Adverse Events or Serious Adverse Events 
There are no disease-related events or disease-related outcomes that are considered as not 
qualifying as AEs or SAEs (i.e., all AEs and SAEs should be reported as indicated in 
Sections 8.8 and 8.10, respectively).  
Deaths with an unknown cause should always be reported as an SAE, but every effort should be 
made to establish a cause of death. 
8.12 
Adverse Event Follow-Up 
All AEs considered to be related to study treatment (see Section 8.9.2) and all SAEs will be 
followed until resolution, until deemed stable by the Investigator, or until the patient is deemed 
by the Investigator to be lost to follow-up. 
8.13 
Pregnancy 
All pregnancies during the study and within 28 days of the last dose of the study treatment 
should be reported to Corcept; the outcomes of pregnancies should be reported to Corcept at the 
term of the gestational period. 


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8.13.1 Maternal Exposure 
If a patient becomes pregnant during the study, study treatment should be discontinued 
immediately. Pregnancy itself is not regarded as an AE unless there is a suspicion that the study 
treatment may have interfered with the effectiveness of a contraceptive medication.  
If any pregnancy occurs during the study or within 28 days of the final dose of the 
investigational product, the Investigator or designee should inform the appropriate Sponsor 
representatives immediately but no later than 24 hours of when he or she becomes aware of it. 
Congenital abnormalities/birth defects and spontaneous miscarriages should be reported and 
handled as SAEs. Elective abortions without complications should not be handled as AEs. The 
outcome of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, 
normal birth, or congenital abnormality) should be followed and documented for up to 2 months 
after the completion of pregnancy even if the patient discontinued the study. 
The designated Sponsor representative works with the Investigator to ensure that all relevant 
information is provided to the Corcept Patient Safety data entry site within 24 hours for SAEs 
(see Section 8.10) and within 28 days for all other pregnancies. The same timelines apply when 
outcome information is available. 
8.13.2 Paternal Exposure 
Pregnancy of the patient’s partner is not considered to be an AE. However, the outcome of all 
pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, or 
congenital abnormality) should be followed and documented, if possible. To capture information 
about a pregnancy from the partner of a male patient, the Investigator or designee must first 
obtain the consent of the male patient’s partner; the male patient should not be asked to provide 
this information. A consent form specific to this situation must be used. The outcome of any 
conception occurring from the date of the first dose until 28 days after the last dose should be 
followed and documented for up to 2 months after the completion of pregnancy. 
8.14 
Treatment of Overdose 
There is currently no experience with overdose of miricorilant. For monitoring symptoms of 
excessive GR and MR antagonism, refer to Section 5.3.3. 
8.15 
Emergency Sponsor Contact 
In a medical emergency (i.e., an event that requires immediate attention regarding the treatment 
of a patient, operation of the clinical study, and/or the use of investigational product), study site 
personnel will apply appropriate medical intervention according to current standards of care and 
contact the Corcept Medical Monitor. 


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9 
STATISTICAL METHODS 
Detailed procedures for statistical analyses to be performed for this study will be provided in a 
separate Statistical Analysis Plan (SAP) that will be finalized before database lock. 
9.1 
Analysis Populations 
The analysis populations are defined in Table 7.  
Table 7 
Definitions of Analysis Populations 
Population 
Description 
All Enrolled  
All patients who meet the study enrollment criteria. 
Safety Population 
All patients who receive at least 1 dose of study medication.  
Intent-to-Treat (ITT) Population 
All patients who receive at least 1 dose of study medication. 
Efficacy Evaluable (EE) 
Population 
All patients who receive ≥4 weeks of study medication and have baseline and 
≥1 body weight measurement taken on or after Week 4. 
PK Population 
All patients who have evaluable PK data. 
 
Summaries of demographics and baseline conditions will be done for the All Enrolled, Safety 
and Efficacy Evaluable (EE) Populations. Analysis of safety data will be performed on the 
Safety Population. Analysis of efficacy data will be performed on the EE Population. Sensitivity 
analyses of the primary and other key endpoints will also be performed on the Intent-to-Treat 
(ITT) Population. 
Pharmacokinetic analyses will be based on the PK Population. Prematurely discontinued patients 
and patients with missing sample concentrations will be included in the PK analyses, provided 
their PK parameters can be adequately characterized based on the remaining data. 
All summaries will be presented by assigned treatment group. In addition, data will be tabulated 
for all patients combined. All relevant data collected on the eCRF will be presented in by-patient 
data listings, to include the site identifier, patient number, and assigned treatment group. 
In general, continuous variables will be summarized by the number of patients with non-missing 
data, mean, standard deviation (SD), median, minimum, and maximum values. Categorical 
variables will be summarized by the number and percentage of patients in each category. 
Predose measurements on Day 1 will be considered the baseline values. If a Day 1 predose value 
is not available, the screening measurement may be used as the baseline value. 
9.2 
Hypothesis Testing 
All statistical hypotheses will be tested at a 2-sided α=0.05 significance level unless otherwise 
specified. 
9.3 
Sample Size Calculation 
Approximately 70 patients will be randomized 1:1 to treatment or placebo in this study. This 
sample size provides 90% power to detect a difference in body weight change of 4 kg between 


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the 600 mg miricorilant dose group and the placebo group. Based on Larsen et al. 2017, which 
examined the effect of liraglutide on olanzapine-and clozapine-treated patients, as well as on 
other studies of AIWG summarized in Mizuno et al. 2014, a standard deviation (SD) of around 
4 to 5 kg can be expected for the difference in body weight change between treatment groups. 
Accordingly, a SD of 4.5 kg is assumed here. Assuming a difference in body weight change 
between groups of 4 kg with an SD of 4.5 kg, and setting α=0.05, 28 patients per group provides 
90% power to detect a significant difference between active dose group and placebo after 
completing 12 weeks of treatment.  
Allowing for 20% dropouts increases the required sample size to 35 patients per group for a total 
of 70 patients in the trial. 
With 35 patients receiving 600 mg miricorilant in the trial, there is a 83% chance that an 
uncommon AE (i.e., an AE expected to occur in only 1 in every 20 patients) will be observed at 
least once during the trial. If a specific AE is never seen in the trial, the 95% upper confidence 
bound on its true incidence would be 10%. 
Randomization will be stratified by the type of antipsychotic medication used [olanzapine, 
risperidone/paliperidone (active risperidone metabolite), quetiapine, aripiprazole, or other]. If at 
least 14 patients complete 12 weeks of treatment (7 patients treated with 600 mg miricorilant and 
7 patients treated with placebo) in one of the allowed antipsychotic medications, this sample size 
provides 50% power to detect a difference in body weight change of 4 kg between 600 mg 
miricorilant and placebo, at alpha=0.1 level for that antipsychotic medication. 
9.4 
Analysis Plan 
9.4.1 Patient Disposition 
Patient disposition summaries will include the number of enrolled patients, the number of 
enrolled patients in each analysis population, the number of patients completing the study per 
protocol, and the number of patients terminating the study early by the primary reason for 
discontinuation. 
9.4.2 Demographic and Baseline Data 
Demographic and baseline data will include frequency and percentages for categorical variables, 
and mean, standard deviation, median, minimum, and maximum for continuous variables. 
Demographic and baseline characteristics will be summarized by treatment group and overall. 
9.4.3 Concomitant Medications 
Verbatim terms on eCRFs will be mapped to Anatomical Therapeutic Chemical class and 
Generic Drug Names using the most current version of the World Health Organization Drug 
Dictionary. Concomitant medications will be summarized for all treatment patients by treatment 
group and overall. 
9.4.4 Safety Analyses 
Adverse events will be mapped to system organ classes and preferred terms using the Medical 
Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs will be summarized 


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overall and displayed by system organ class and preferred term, as well as by severity, 
seriousness, and relationship to the study treatment. Serious AEs and AEs that lead to study 
treatment discontinuation or withdrawal from the study will be listed by individual patient. 
Clinical laboratory test results (chemistry, hematology, and coagulation), vital sign 
measurements, physical examination findings, and ECG results will be summarized by visit 
using descriptive statistics. Shift tables will be constructed that describe changes from baseline in 
clinical laboratory values. 
9.4.5 Efficacy Analyses 
Efficacy analyses will be performed on the EE Population. Sensitivity analyses of the primary 
and other key endpoints will be performed on the ITT Population (see Table 7 for definitions of 
analysis populations). 
9.4.5.1 
Primary Efficacy Analysis 
The primary efficacy endpoint is the change in body weight from baseline to Week 12. All 
values for body weight will be used in the analysis. For patients who discontinue treatment prior 
to Week 12 and do not have the Week 12 body weight available, a retrieved dropout approach 
will be used. The primary endpoint will be assessed using a mixed-effect model with repeated 
measures (MMRM) with change in body weight at each visit as the outcome variable; baseline 
body weight and antipsychotic medication (stratification factor) as covariates; and randomized 
treatment (600 mg miricorilant or placebo), visit, and treatment-by-visit interaction as fixed 
effects. The difference in body weight change between miricorilant and placebo will be 
estimated from the model along with its 95% confidence interval (CI).  
9.4.5.2 
Sensitivity Analysis of Primary Endpoint 
The MMRM used to assess the primary endpoint will be rerun as a sensitivity analysis using the 
ITT Population in place of the EE Population. 
9.4.5.3 
Secondary Efficacy Analyses 
The secondary efficacy endpoints are defined in Section 3.2.3. 
The percentage of patients in each treatment group who lose ≥5% of their baseline body weight 
will be presented along with its 95% CI. In addition, a logistic regression model with baseline 
body weight and stratification factor as covariates will be used to compare miricorilant to 
placebo. 
HOMA-IR will be calculated using the approximate formula (Matthews et al. 1985):  
HOMA-IR=(glucose (mg/dL) × insulin (µU/mL))/405  
HOMA-IR and waist-to-hip ratio will be analyzed using similar models as the primary analysis 
of weight change. Both HOMA-IR and waist-to-hip ratio may be log-transformed prior to 
analysis. Model estimates derived from log-transformed data will be back-transformed to the 
original scale for presentation of the treatment effect of miricorilant compared to placebo. For 
patients who discontinue treatment prior to Week 12 and do not have the Week 12 HOMA-IR or 


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waist-to-hip ratio available, a retrieved dropout approach will be used similar to the primary 
efficacy analysis. 
9.4.6 Pharmacokinetic Analysis 
The PK variables for analysis are listed in Table 8; details of the PK analyses will be described in 
a PK analysis plan finalized before database lock. 
The PK data obtained from the PK substudy, including the PK parameters of miricorilant 
estimated by noncompartmental methods, will be summarized descriptively. The 95% CIs for the 
PK parameters will be presented. Additionally, plasma concentrations of miricorilant will be 
plotted over time. 
Table 8 
Pharmacokinetic Variables for Analysis 
λz 
apparent terminal rate constant  
AUC 
area under the concentration-time curve 
AUClast 
AUC values from time 0 to time of last measurable concentration 
AUCtau 
AUC over the dosing interval 
Cmax 
maximum concentration over the dosing interval 
Ctau 
concentration at the end of the dosing interval 
t1/2 
apparent terminal elimination half-life 
tlast  
time of the last quantifiable concentration 
Tmax 
time to maximum concentration 
 
9.4.7 Exploratory Analysis  
Analyses of continuous endpoints, such as the change in BPRS, CGI, MADRS-SIGMA, YMRS, 
ACTH, and serum cortisol from baseline to Week 12 will be analyzed using similar models as 
the primary analysis of body weight change. C-SSRS results will be summarized descriptively. 
Changes in HbA1c and fasting blood glucose within patients with diabetes will employ pairwise 
Wilcoxon rank-sum tests to compare treatment groups. A similar strategy will be used to 
compare groups on the change from baseline in blood pressure among patients with high blood 
pressure. 
Exploratory analyses will be described in the SAP finalized before database lock. 
9.4.8 Pharmacogenetic Analysis 
Not applicable. 
9.4.9 Interim Analysis 
Not applicable. 


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10 
ETHICAL AND LEGAL CONSIDERATIONS 
10.1 
Compliance with IRB Regulations 
This study is to be conducted in accordance with IRB regulations (US 21 CFR Part 56.103) and 
applicable local regulations. The protocol, ICFs, recruitment materials, and all patient materials 
will be submitted to the IRB for review and approval. Approval of both the protocol and the 
consent form must be obtained before any patient is enrolled. The Investigator is responsible for 
informing the IRB of any amendment to the protocol in accordance with local requirements. The 
protocol must be re-approved by the IRB on receipt of amendments and annually, as local 
regulations require. 
All changes to the consent form must be approved by the IRB; a determination will be made 
regarding whether previously consented patients need to be re-consented. 
Corcept is to be notified immediately if the responsible IRB has been disqualified or if 
proceedings leading to disqualification have begun. Copies of all IRB correspondence with the 
Investigator should be provided to Corcept. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
according to local regulations and guidelines. 
10.2 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP and applicable regulatory 
requirements. 
The Investigator will ensure that the study procedures outlined in this protocol will be conducted 
in accordance with applicable country and local regulations. 
10.3 
Protection of Human Patients 
10.3.1 Compliance with Informed Consent Regulations  
Written informed consent is to be obtained from each patient before enrollment into the study.  
The Investigator(s) at each center will ensure that the patient is given full and adequate oral and 
written information about the nature, purpose, possible risk, and benefit of the study. Patients 
must also be notified that they are free to discontinue from the study at any time. The patient 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. 
• The ICF will contain all of the elements required by ICH guidelines for GCP and any 
additional elements required by local regulations. 
• The ICF must include information about the possible retention of biological samples at 
the conclusion of this study; with the patient’s permission, samples may be retained for 
future determination of active metabolite concentrations and possible biomarkers related 
to drug response. 
• The patient’s signed and dated ICF must be obtained before conducting any study 
procedures. 


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• The ICF must include information about the possible retention of biological samples at 
the conclusion of this study; with the patient’s permission, blood, plasma, serum and 
tissue samples may be obtained for future analysis to help identify biomarkers of disease 
or miricorilant treatment. 
The Investigator(s) must maintain the original, signed ICF. A copy of the signed ICF must be 
given to the patient. 
10.3.2 Patient Confidentiality 
To maintain patient privacy, all source documents, study reports, and communications will 
identify the patient by initials and the assigned patient number. The Investigator will grant 
monitor(s) and auditor(s) from Corcept or Corcept’s designee and regulatory authority(ies) 
access to the patient’s original study records for verification of data gathered on source 
documents and to audit the data collection process. The patient’s confidentiality will be 
maintained and their personal data will not be made publicly available to the extent permitted by 
applicable laws and regulations. 
10.3.3 Patient Privacy 
The Investigator or designee must explain to each patient, before enrollment into the study, that 
for evaluation of study results, the patient’s protected health information obtained during the 
study may be shared with Corcept, regulatory agencies, and IRB. It is the Investigator’s (or 
designee’s) responsibility to obtain written permission to use protected health information per 
country-specific regulations from each patient. If permission to use protected health information 
is withdrawn, it is the Investigator’s responsibility to obtain a written request, to ensure that no 
further data will be collected from the patient, and the patient will be removed from the study. 
Written authorization is to be obtained from each patient before enrollment into the study in 
accordance with the applicable privacy requirements. 


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11 
ADMINISTRATIVE CONSIDERATIONS 
11.1 
Study Monitoring 
Monitoring of study sites (including, but not limited to, reviewing eCRFs for accuracy and 
completeness, and assessing compliance with the protocol and adherence to regulatory and GCP 
requirements) will be performed by Corcept’s Clinical Monitor or designee. 
• Monitoring will be performed in accordance with applicable federal regulations and 
guidance. 
• Monitoring will include regular site visits and communication with the Investigator and 
site staff as appropriate to discuss and answer study questions; ensure compliance with 
the protocol; and ensure quality and integrity of the data. 
• Monitors will ensure sites maintain an adequate supply of investigational products and 
any necessary supplies and ensure that appropriate storage conditions are maintained. 
• Monitoring visits will be conducted according to the US CFR Title 21 parts 50, 56, and 
312 and ICH Guideline for GCP. 
Monitoring methods, responsibilities, and requirements will be outlined in a monitoring plan. 
11.2 
Quality Management 
Study sites, the study database, and study documentation will be monitored regularly and may be 
subject to a quality assurance audit during the study by Corcept or its designee on behalf of 
Corcept. In addition, inspections may be conducted by regulatory agencies at their discretion. 
Quality control procedures will be implemented beginning with the data entry system and data 
quality control checks that will be run on the database will be generated. Any missing data or 
data anomalies will be communicated to the site(s) for clarification/resolution. 
Following written standard operating procedures, the monitors will verify that the clinical trial is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
protocol, GCP, and the applicable regulatory requirements (e.g., GLP and Good Manufacturing 
Practices). 
The investigational site will provide direct access to all trial-related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by Corcept, and inspection by local and 
regulatory authorities. 
11.3 
Documentation 
11.3.1 Case Report Forms and Study Records 
The Investigator must generate and maintain complete, adequate, accurate, reliable, and 
consistent records to enable full documentation of study conduct. Study data will be captured 
in an EDC system on eCRFs. Investigators must retain all original source documents, and 
Corcept or its designee will notify Investigators in writing when the trial-related records are 
no longer needed. 


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11.3.2 Access to Source Documentation 
Corcept or its representative will be allowed to conduct site visits to the investigational facilities 
for the purpose of monitoring any aspect of the study. By signing the protocol, the Investigator 
agrees that, within local regulatory restrictions and institutional and ethical considerations, 
authorized representatives of Corcept, a regulatory authority, and/or an IRB may visit the site to 
perform audits or inspections, including the drug storage area, study drug stocks, drug 
accountability records, patient charts, source documents, and other records relative to study 
conduct. The purpose of a Sponsor audit or inspection is to systematically and independently 
examine all study-related activities and documents (e.g., laboratory reports, x-rays, workbooks, 
and patients’ medical records) to determine whether these activities were conducted, and data 
recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of the 
ICH, and any applicable regulatory requirements. 
The Investigator should contact Corcept immediately if contacted by a regulatory agency 
regarding an inspection. 
11.3.3 Source Documents 
Source documents provide all original records of clinical findings, observations, or other 
information from a clinical trial necessary for the reconstruction and evaluation of the trial (e.g., 
a patient’s medical records, hospital charts, and clinic charts; the Investigator’s patient study 
files; results of diagnostic tests, including laboratory tests and ECGs). All source data should be 
attributable, legible, contemporaneous, original, accurate, and completed. Changes to source data 
should be traceable, should not obscure the original entry, and should be explained, if necessary.  
Investigators must retain all original source documents. The Sponsor or its designee will notify 
Investigators in writing when the trial-related records are no longer needed. 
11.3.4 Study Files and Retention of Study Records 
The Investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. 
Study documents should be retained for a minimum of 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 until 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 local regulations. No records will be 
destroyed without the written consent of Corcept, if applicable. It is the responsibility of Corcept 
to inform the Investigator when these documents no longer need to be retained. 
Patient identification codes (patient names and corresponding study numbers) will be retained for 
this same period of time. These documents may be transferred to another responsible party, 
acceptable to Corcept, who agrees to abide by the retention policies. Written notification of 
transfer must be submitted to Corcept. The Investigator or designee must contact Corcept before 
disposing of any study records. 


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11.4 
Long-Term Retention of Biological Samples 
No samples will be retained long term (ie, beyond clinical study report) without prior written 
consent of the subject and IRB or IEC approval. All long-term retention samples will be retained 
by Corcept or designee. The long-term retention samples will be coded to allow de-identification 
according to applicable regulatory guidelines. 
After conclusion of this study, the long-term samples will be held for a period up to 10 years, 
after which they will be destroyed. During the conduct of the study, an individual subject can 
choose to withdraw consent to have his or her samples stored for future research; however, 
withdrawal of consent with regard to biological sample storage will not be possible after the 
study is completed. 
11.5 
Clinical Supplies 
11.5.1 Inventory, Reconciliation, Return, and Disposition of Clinical Supplies 
All study drug and related materials should be stored, inventoried, reconciled, and destroyed or 
returned according to applicable state and federal regulations and study procedures. Storage of 
study drug is described in Table 1. 
11.5.2 Clinical-Supply Inventory 
A detailed inventory must be completed for all study drug. The study drug is to be used in 
accordance with the protocol by patients who are under the direct supervision of an Investigator. 
The study drug must be dispensed only by an appropriately qualified person to patients in 
the study. 
Unused study drug must be kept in a secure location for accountability and reconciliation by the 
study monitor. The Investigator or designee must provide an explanation for any destroyed or 
missing study drug or study materials. 
The Investigator or designee is responsible for maintaining accurate records (including dates and 
quantities) of study drug(s) received, patients to whom study drug is dispensed (patient-by-
patient dose-specific accounting), and study drug lost or accidentally or deliberately destroyed. 
The Investigator or designee must retain all unused or expired study supplies until the study 
monitor (on-site clinical research associate) has confirmed the accountability data and Corcept 
has approved return or destruction. 
11.5.3 Return or Disposal of Study Drug and/or Supplies 
All clinical study drug and/or supplies will either be destroyed by the site per institutional policy 
or be returned to Corcept or Corcept’s designee for destruction. 
Unused study drug may be destroyed on site, per the site’s standard operating procedures, but 
only after Sponsor has granted approval for drug destruction. The monitor must account for all 
study drug in a formal reconciliation process, before study-drug destruction. All study drug 
destroyed on site must be documented.  
Documentation must be provided to Corcept and retained in the Investigator study files. If a site 
is unable to destroy study drug appropriately, the site can return unused study drug to Corcept 


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upon request. The return of study drug or study drug materials must be accounted for on a Study 
Drug Return Form provided by Corcept. 
11.6 
Drug Accountability 
It is the responsibility of the Investigator to maintain drug accountability at the study site and 
ensure that a current record of investigational product disposition is maintained. It is the 
responsibility of the Investigator to ensure that the investigational product is used only in 
accordance with the approved protocol. This includes acknowledgment of receipt of each 
shipment of study product (quantity and condition), patient dispensing records, and returned or 
destroyed study product. Dispensing records will document quantities received from Corcept (or 
Corcept’s designee) and quantities dispensed to patients, including lot number, date dispensed, 
patient identifier number, patient initials, and the initials of the person dispensing the drug. At 
the end of the study, after final drug inventory reconciliation by the monitor, the study site will 
dispose of and/or destroy all unused investigational medicinal product supplies, including empty 
containers, according to standard procedures. 
11.7 
Post-trial Care 
There is no provision for continuation of the investigational drug beyond the end of study 
treatment. Corcept will work with the Investigator to ensure that study participants continue to 
receive appropriate care, which may include referral to an ongoing clinical trial or another 
investigational treatment or may involve transition to medical management outside the 
research context. 
11.8 
Noncompliance with the Protocol 
Prospective approval of deviations from the inclusion and exclusion criteria, also known as 
protocol waivers or exemptions, is not permitted. 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or manual of 
procedures requirements. The noncompliance may be either on the part of the patient, the 
Investigator, or the study site staff. As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. These practices are consistent with ICH E6. 
The Investigator should not implement any deviation from the protocol without prior review and 
agreement by Corcept in writing and in accordance with the IRB and local regulations, except 
when necessary to eliminate an immediate hazard to study patients. When a deviation from the 
protocol is deemed necessary for an individual patient, the Investigator must obtain approval in 
writing from Corcept. 
Such contact must be made as soon as possible to permit a review by Corcept to determine the 
impact of the deviation on the patient and/or the study. 
Any significant protocol deviations affecting patient eligibility and/or safety must be reviewed 
and/or approved by the IRB and regulatory authorities, as applicable, prior to implementation. 


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11.9 
Financial Disclosure 
Investigators will be required to disclose any financial equity interests in Corcept and any 
conflicts of interest, as defined by Corcept. 
11.10 Publication and Disclosure Policy 
Corcept, as the Sponsor, has a proprietary interest in this study. 
No individual publications will be allowed before publication of the multicenter results except as 
agreed with Corcept. The Investigator agrees to submit all manuscripts or abstracts to Corcept 
for review before submission to the publisher. 
Corcept will comply with the requirements for publication of study results and determination of 
authorship in accordance with standard editorial and ethical practice and with the International 
Committee of Medical Journal Editors requirements. 
11.11 Final Report Signature 
Corcept’s responsible Medical Officer will approve the final clinical study report for this study, 
confirming that, to the best of his or her knowledge, the report accurately describes the conduct 
and results of the study. 


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12 
REFERENCES 
ADA/APA/AACE/NAASO (American Diabetes Association, American Psychiatric Association, 
American Association of Clinical Endocrinologists, and North American Association for 
the Study of Obesity). 2004. Consensus Development Conference on Antipsychotic 
Drugs and Obesity and Diabetes. Diabetes Care 27(2):596–601. 
AHA (American Heart Association). https://www.heart.org/idc/groups/heart-
public/@wcm/@hcm/documents/downloadable/ucm_300467.pdf  
Allison DB1, Casey DE. 2001. Antipsychotic-induced weight gain: a review of the literature. J 
Clin Psychiatry 62 Suppl 7:22–31. 
Annamalai A. 2017. Prevalence of obesity and diabetes in patients with schizophrenia. World J 
Diabetes 8(8):390–396. 
Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA. 2017. 
Antipsychotic-associated weight gain: management strategies and impact on treatment 
adherence. Neuropsychiatr Dis Treat. 13:2231–2241. 
Gothelf D, Falk B, Singer P, Kairi M, Phillip M, Zigel L, et al. 2002. Weight gain associated 
with increased food intake and low habitual activity levels in male adolescent 
schizophrenic inpatients treated with olanzapine. Am J Psychiatry 159(6):1055–1057. 
Graham KA, Perkins DO, Edwards LJ, Barrier RC, Lieberman JA, Harp JB. 2005. Effect of 
olanzapine on body composition and energy expenditure in adults with first-episode 
psychosis. Am J Psychiatry 162(1):118–123. 
Gross C, Blasey CM, Roe RL, Allen K, Block TS, Belanoff JK. 2009. Mifepristone treatment of 
olanzapine-induced weight gain in healthy men. Adv Ther. 26(10):959–969. 
Gross C, Blasey CM, Roe RL, Belanoff JK. 2010. Mifepristone reduces weight gain and 
improves metabolic abnormalities associated with risperidone treatment in normal men. 
Obesity 18(12):2295–2300. 
Hamman RF, Wing RR, Edelstein SL, Lachin JM, Bray GA, Delahanty L, et al. 2006. Effect of 
weight loss with lifestyle intervention on risk of diabetes. Diabetes Care 29(9):2102–
2107. 
Hunt HJ, Ray NC, Hynd G, Sutton J, Sajad M, O’Connor E, et al. 2012. Discovery of a novel 
non-steroidal GR antagonists with in vivo efficacy in the olanzapine-induced weight gain 
model in the rat. Bioorg Med Chem Lett. 22:7376–7380. 
Larsen JR, Vedtofte L, Jakobsen MSL. 2017. Effect of liraglutide treatment on prediabetes and 
overweight or obesity in clozapine- or olanzapine-treated patients with schizophrenia 
spectrum disorder. JAMA Psychiatry 74(7):719–728. 
Laursen TM, Munk-Olsen T, Vestergaard M. 2012. Life expectancy and cardiovascular mortality 
in persons with schizophrenia. Curr Opin Psychiatry 25(2):83–88. 


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Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al; Clinical 
Antipsychotic Trials or Intervention Effectiveness (CATIE) Investigators. 2005. 
Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J 
Med. 353(12):1209–1223. 
Maayan L, Vakhrusheva J, Correll CU. 2010. Effectiveness of medications used to attenuate 
antipsychotic-related weight gain and metabolic abnormalities: a systematic review and 
meta-analysis. Neuropsychopharmacology 35(7):1520–1530. 
Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner RC. 1985. Homeostasis 
model assessment: insulin resistance and beta-cell function from fasting plasma glucose 
and insulin concentrations in man. Diabetologia 28(7): 412–419. 
McIntyre RS, Deborah A. Mancini DA, Basile VS, Srinivasan J, Kennedy SH. 2003. 
Antipsychotic-Induced Weight Gain: Bipolar Disorder and Leptin. J Clin 
Psychopharmacol 23:323–327.  
Mizuno Y, Suzuki T, Nakagawa A, Yoshida K, Mimura M, Fleischhacker WW, et al. 2014. 
Pharmacological strategies to counteract antipsychotic-induced weight gain and 
metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. 
Schizophr Bull. 40(6):1385–1403. 
Mukundan A, Faulkner G, Cohn T, Remington G. 2010. Antipsychotic switching for people with 
schizophrenia who have neuroleptic-induced weight or metabolic problems. Cochrane 
Database Syst Rev. 12:CD006629. DOI: 10.1002/14651858.CD006629.pub2. 
Narasimhan M, Bruce TO, Masand P. 2007. Review of olanzapine in the management of bipolar 
disorders. Neuropsychiatr Dis Treat. 3(5):579–587. 
NCI (National Cancer Institute). 2017. Common Terminology Criteria for Adverse Events, 
version 5.0 published: November 27, 2017. US Department of Health and Human 
Services, National Institutes of Health, Accessed at https://ctep.cancer.gov/protocol 
Development/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf 
Nashed MG, Restivo MR, Taylor VH. 2011. Olanzapine-induced weight gain in patients with 
bipolar I disorder: a meta-analysis. Prim Care Companion CNS Disord 
13(6):PCC.11r01174. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. 2011. The 
Columbia-Suicide Severity Rating Scale: initial validity and internal consistency 
findings from three multisite studies with adolescents and adults. Am J Psychiatry 
168(12):1266–1277. 
Torrent C, Amann B, Sanchez-Moreno J, Colom F, Reinares M, Comes M, Rosa AR, Scott J, 
Vieta E. 2008. Weight gain in bipolar disorder: pharmacological treatment as a 
contributing factor. Acta Psychiatr Scand 118: 4–18. 
Tulipano G, Rizzetti C, Bianchi I, Fanzani A, Spano P, Cocchi D. 2007. Clozapine-induced 
alteration of glucose homeostasis in the rat: the contribution of hypothalamic-pituitary-
adrenal axis activation. Neuroendocrinology 85:61–70. 


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Van der Zwaal E, Jahunen S, la Fleur S, Adan R. 2014. Modelling olanzapine-inducted weight 
gain in rats. International Journal of Neuropsychopharmacology 17:169–186. 
 


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13 
APPENDICES 
 


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Appendix A: Schedule(s) of Assessments 
Table 9 
Schedule of Clinical Assessments and Procedures 
 
 
 
Treatment Period 
ET a 
Follow-up 
28±5 days after 
last dose of study 
drug 
Assessment 
Screening 
Days−28 
to−1 
Baseline 
Day 1 
Week 1 
Day 8±2 
days 
Week 2 
Day 15±2 
days 
Week 4 
Day 29±2 
days 
Week 6 
Day 43±2 
days 
Week 8 
Day 57±2 
days 
Week 10 
Day 71±2 
days 
Week 12 
Day 85±2 
days 
Informed consent b 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria b 
X 
 
 
 
 
 
 
 
 
 
 
Medical history and prior 
medications c 
X  
 
 
 
 
 
 
 
 
 
 
Swallow assessment 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
Record AEs c 
 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test d 
X 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test d 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FSH test e 
X 
 
 
 
 
 
 
 
 
 
 
Urine drug test 
X 
X 
 
 
 
 
 
 
 
 
 
Diet and exercise counseling 
 
X 
 
 
 
X 
 
 
 
 
 
Physical examination f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body weight  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs (including orthostatic 
vital signs) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead resting ECG (in 
triplicate) g 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Waist-to-hip ratio 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispensing of study treatment 
(tablets) 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Accounting of unused tablets 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dose diary provided 
 
X 
 
 
 
 
 
 
 
 
 
Dose diary (assessed and 
returned to patient) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 


Protocol CORT118335-876 (GRATITUDE)
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Treatment Period 
ET a 
Follow-up 
28±5 days after 
last dose of study 
drug 
Assessment 
Screening 
Days−28 
to−1 
Baseline 
Day 1 
Week 1 
Day 8±2 
days 
Week 2 
Day 15±2 
days 
Week 4 
Day 29±2 
days 
Week 6 
Day 43±2 
days 
Week 8 
Day 57±2 
days 
Week 10 
Day 71±2 
days 
Week 12 
Day 85±2 
days 
Virus screen (HCV, HBV) 
X 
 
 
 
 
 
 
 
 
 
 
Hematology with platelet and 
WBC differential 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
Chemistry h  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panel i 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
HbA1c 
X 
X 
 
 
 
 
 
 
X 
X 
 
Serum insulin, fasting 
 
X 
 
 
 
 
 
 
X 
X 
 
Plasma glucose, fasting 
 
X 
 
 
 
 
 
 
X 
X 
 
TSH 
X 
X 
 
 
 
 
 
 
X 
X 
 
Free T4 
X 
X 
 
 
 
 
 
 
X 
X 
 
ACTH (morning–8 AM) 
 
X 
 
 
X 
 
 
 
X 
X 
 
Serum cortisol (morning–8 AM) 
 
X 
 
 
X 
 
 
 
X 
X 
 
Glucocorticoid receptor activity 
marker 
 
X 
 
 
 
 
 
 
X 
X 
 
MINI  
X 
 
 
 
 
 
 
 
 
 
 
DSM-5 bipolar disorder 
assessment 
X 
 
 
 
 
 
 
 
 
 
 
BPRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
C-SSRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CGI 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
YMRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MADRS-SIGMA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK substudy j 
 
 
 
 
X 
 
 
 
 
 
 
Abbreviations: ACTH, adrenocorticotropic hormone; AE, adverse event; BPRS, Brief Psychiatric Rating Scale; CGI, Clinical Global Impression, C-SSRS, 
Columbia-Suicide Severity Rating Scale; DSM-5, American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders; ECG, 
electrocardiogram; ET, early termination; FSH, follicle-stimulating hormone; HbA1c, glycated hemoglobin; ICF, informed consent form; MADRS-SIGMA, 
Montgomery-Åsberg Depression Rating Scale; MINI, Mini International Neuropsychiatric Interview; PK, pharmacokinetic; T4, thyroxine; TSH, thyroid-
stimulating hormone; WBC, white blood cell (count); YMRS. Young Mania Rating Scale. 
a. Patients who discontinue the study drug before the end of the Treatment Period will be asked to complete the ET visit at the time of the last dose of study drug 
(or soon thereafter); Follow-Up visit will be conducted 28±5 days after the last dose of study drug. 
b. Confirm informed consent was obtained and patient meets inclusion/exclusion criteria prior to randomization at Baseline Day 1 Visit. 


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c. Illnesses present before the patient signs the ICF are considered pre-existing conditions and are to be documented on the medical history eCRF. Illness/events 
that occur after patient signs the consent and pre-existing conditions that worsen will be recorded as AEs. 
d. Serum and urine pregnancy tests will be completed on all women of child-bearing potential. If urine pregnancy test is positive, the result should be confirmed 
with a serum pregnancy test. 
e. An FSH test will be completed on women who have medically confirmed ovarian failure or are postmenopausal. Menopause is defined as cessation of regular 
menses for at least 12 consecutive months with no alternative pathological or physiological cause, and an FSH level within the laboratory’s reference range for 
a postmenopausal woman. 
f. All physical examinations should include a basic neurological exam. 
g. At Baseline, the 12-lead resting ECG (in triplicate) will be performed both before dosing and 2 hr ±15 min after dosing. 
h. Fasting chemistry panels will occur on Screening, Baseline, Week 12 and ET. All other chemistry panels will be done non-fasting  
i. Lipid panel to include cholesterol, triglycerides, direct low-density lipoprotein (LDL), very-low density LDL (VLDL) and high-density lipoprotein (HDL). 
Fasting lipid panels will occur on Screening, Baseline, Week 12, and ET. All other lipid panels will be done non-fasting. 
j. Blood samples will only be collected from patients who consent to participate in the PK substudy, at the time points specified in the PK plan outlined in the 
study manual. Note: Patients will be required to take their dose of study treatment both the day prior and the day of their Week 4 visit in the clinic (witnessed 
dosing). 


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Amendment 5  |  11 January 2022 
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Appendix B: Summary of Changes 
Significant changes in Amendment 5 of the protocol dated 11 January 2022 compared with the 
Amendment 4 dated 03 August 2021 are summarized below with additional details in Table 10; 
deleted text is shown as a strikethrough and new text is shown in bold.  
Minor editorial or stylistic changes made for consistency are not summarized and may not be 
shown in the redline version of the amendment (e.g., punctuation, spelling, abbreviations). 
Throughout the document, sections, tables, and figures were renumbered as appropriate. Table of 
Contents, lists of tables or figures are updated without redline.  
Significant revisions to the protocol include the following: 
• Stopping criteria for study drug in case of suspected liver injury was modified per IDMC 
recommendations. 
• Change in number of patients planned for the study. 
 


Protocol CORT118335-876 (GRATITUDE)
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Table 10 
Summary of Changes in Protocol CORT118335-876 Amendment 5  
Section 
Summary of 
Change 
Revisions 
Global changes  
Updated version 
and date of the 
protocol. 
Amendment 4Amendment 5 
03 August 202111 January 2022 
Synopsis 
Updated text in 
synopsis to align 
with changes in 
the protocol body. 
-- 
1.4.2 Design 
Considerations 
Modified the 
expected number 
of patients to be 
randomized in the 
study. 
Paragraph 1: 
This is a Phase 2, randomized, double-blind, placebo-controlled study to 
evaluate the safety, efficacy, and PK of miricorilant. This study will be 
conducted in the USA, at approximately 35 sites, and will randomize 
approximately 10070 patients with schizophrenia or bipolar disorder who 
have recent AIWG (see Section 4.1, exclusion criterion #6) in a 1:1 ratio to 
600 mg miricorilant or placebo. 
3.1 Overall 
Design 
Modified study 
design to align 
with changes to 
expected number 
of patients to be 
randomized. 
CORT118335-876 Study Design (Figure 3) updated. 
3.3.1 Number of 
Patients 
Modified the 
expected number 
of patients to be 
randomized in the 
study. 
Paragraph 1: 
Approximately 100 70 patients will be randomized in this study, with a 
target of randomizing 5035 patients in each treatment group: 600 mg 
miricorilant and placebo. See Section 9.3 for details regarding sample size 
calculation. See Section 4.5 for details regarding replacement of patients. 
5.3.3 Dose 
Interruption 
and/or 
Discontinuation: 
Special Safety 
Events 
In Table 2, 
stopping criteria 
for study drug in 
case of suspected 
liver injury was 
modified per 
IDMC 
recommendations. 
Table 2: 
Row 4: 
Suspected 
liver 
injury 
Criteria: AST or ALT > 3 × 
ULN or total bilirubin > 
2.0 × ULN while on study 
drug  
Management: 
• Repeat liver 
biochemistries (ALT, 
AST, alkaline 
phosphatase, total 
bilirubin) within 48 to 
72 hours of results.  
• Obtain a more detailed 
history of symptoms and 
prior or concurrent 
disease and a history of 
concomitant drug use 
(including 
Study drug will be stopped 
if:  
• ALT or AST > 8 × ULN.  
• ALT or AST > 5 × ULN 
for more than 2 weeks.  
• ALT or AST > 3 × ULN 
and (TBL >2 × ULN or 
INR >1.5).  
• ALT or AST > 3 × ULN 
with the appearance of 
fatigue, nausea, vomiting, 
right upper quadrant pain 
or tenderness, fever, rash, 
and/or eosinophilia 
(>5%). 


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Page 89 
Section 
Summary of 
Change 
Revisions 
nonprescription 
medication and herbal and 
dietary supplement 
preparations). 
• Obtain a history of 
exposure to environment 
chemical agents. 
• Rule out other causes of 
liver disease.  
• Obtain additional tests to 
evaluate liver function, as 
appropriate (e.g., INR, 
direct bilirubin). 
• Continue to monitor the 
liver biochemistry two or 
three times weekly but no 
less frequently than once 
weekly. Frequency can 
decrease to once a week 
or less if abnormalities 
stabilize, or study drug 
has been discontinued and 
the patient is 
asymptomatic. 
• Consider a 
gastroenterology or 
hepatology consultation. 
• During the period of close 
observation, study drug 
can be continued if 
desired at the discretion 
of Corcept Medical 
Monitor and Investigator 
unless one of the criteria 
for stopping study 
treatment are met. 
5.4.3 Prohibited 
Medications 
Updated the list 
of prohibited 
medications to 
include inhaled 
corticosteroids. 
The following medications are prohibited during treatment with miricorilant 
in this study: 
…. 
Bullet 6: 
• Systemic corticosteroids, including inhaled corticosteroids [(with 
exception of temporary use for treatment of excessive GR antagonism]), 
potent (group III) topical corticosteroids, and intra-articular 
corticosteroids 


Protocol CORT118335-876 (GRATITUDE)
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Amendment 5  |  11 January 2022 
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Page 90 
Section 
Summary of 
Change 
Revisions 
8.10 Procedures 
for Reporting a 
Serious Adverse 
Event 
Text updated to 
remove reference 
to cover page 
with respect to the 
Medical Monitor. 
Any SAE occurring from the time of informed consent and for ≤28 days 
after the last dose of study treatment must be reported within 24 hours to the 
Corcept Medical Monitor listed on the cover page and recorded on the SAE 
Form. All patients with an SAE must be followed and the outcomes 
reported. The Investigator must supply Corcept and the IRB with any 
additional requested information (e.g., autopsy reports and terminal medical 
reports). 
8.15 Emergency 
Sponsor Contact 
Text updated to 
remove reference 
to cover page 
with respect to the 
Medical Monitor. 
In a medical emergency (i.e., an event that requires immediate attention 
regarding the treatment of a patient, operation of the clinical study, and/or 
the use of investigational product), study site personnel will apply 
appropriate medical intervention according to current standards of care and 
contact the Corcept Medical Monitor listed on the cover page. 
9.3 Sample Size 
Calculation 
Updated text to 
reflect changes in 
sample size.  
Approximately 10070 patients will be randomized 1:1 to treatment or 
placebo in this study. This sample size provides 90% power to detect a 
difference in body weight change of 54 kg between the 600 mg miricorilant 
dose group and the placebo group. Based on Larsen et al. 2017, which 
examined the effect of liraglutide on olanzapine-and clozapine-treated 
patients, as well as on other studies of AIWG summarized in Mizuno et al. 
2014, a standard deviation (SD) of around 4 to 5 kg can be expected for the 
difference in body weight change between treatment groups. Accordingly, a 
conservative SD of 64.5 kg is assumed here. Assuming a difference in body 
weight change between groups of 54 kg with an SD of 64.5 kg, and setting 
α=0.05, 3028 patients per group provides 90% power to detect a significant 
difference between active dose group and placebo after completing 12 
weeks of treatment.  
Allowing for 4020% dropouts increases the required sample size to 5035 
patients per group for a total of 10070 patients in the trial. 
With 5035 patients receiving 600 mg miricorilant in the trial, there is a 
9283% chance that an uncommon AE (i.e., an AE expected to occur in only 
1 in every 20 patients) will be observed at least once during the trial. If a 
specific AE is never seen in the trial, the 95% upper confidence bound on its 
true incidence would be 6.410%. 
Randomization will be stratified by the type of antipsychotic medication 
used [olanzapine, risperidone/paliperidone (active risperidone metabolite), 
quetiapine, aripiprazole, or other]. If at least 2014 patients complete 12 
weeks of treatment (107 patients treated with 600 mg miricorilant and 107 
patients treated with placebo) in one of the allowed antipsychotic 
medications, this sample size provides 6050% power to detect a difference 
in body weight change of 54 kg between 600 mg miricorilant and placebo, 
at alpha=0.1 level for that antipsychotic medication. 
 
 
 

SAP_001.pdf: 
Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, 
Efficacy, and Pharmacokinetics of Miricorilant (CORT118335) in Obese Adult Patients with 
Schizophrenia or Bipolar Disorder and Recent Weight Gain While Taking Antipsychotic 
Medications (GRATITUDE) 
 
NCT Number: NCT03818256 
 
Date: 27 July 2022 








  
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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACTH 
adrenocorticotropic hormone 
AIWG 
antipsychotic-induced weight gain 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
BMI 
body mass index 
BPRS 
brief psychiatric rating scale 
CGI 
clinical global impression scale 
CGI-I 
clinical global impression - improvement 
CGI-S 
clinical global impression - severity 
CI 
confidence interval 
COVID-19 
Coronavirus disease 2019 
CRO 
contract research organization 
CSR 
clinical study report 
C-SSRS 
Columbia-suicide severity rating scale 
CTCAE 
common terminology criteria for adverse events 
DBP 
diastolic blood pressure 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eDISH 
Evaluation of Drug-Induced Serious Hepatotoxicity 
GGT 
gamma glutamyl transferase 
GR 
glucocorticoid receptor 
HbA1c 
glycated hemoglobin  
HDL 
high-density lipoprotein 
HOMA-IR 
homeostatic model assessment for insulin resistance 
ICH 
International Council for Harmonisation 
INR 
international normalized ratio 
IWRS 
interactive web response system 
LDL 
low-density lipoprotein 


  
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 Statistical Analysis Plan v1.0 | 27 July 2022 
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Page 5 
Abbreviation 
Definition 
LLOQ 
lower limit of quantification 
LOCF 
last observation carried forward 
MADRS 
Montgomery-Asberg depression rating scale 
MAR 
missing at random 
MedDRA 
medical dictionary for regulatory activities 
MMRM 
mixed-effect model with repeated measures 
MR 
mineralocorticoid receptor 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
PT 
preferred term 
REML 
restricted maximum likelihood 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SDTM 
Study Data Tabulation Model 
SI 
Système International 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
ULOQ 
upper limit of quantification 
VLDL 
very low-density lipoprotein 
WHO 
World Health Organization 
YMRS 
Young mania rating scale 
 


  
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 Statistical Analysis Plan v1.0 | 27 July 2022 
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Page 6 
CONTENTS 
STATISTICAL ANALYSIS PLAN (SAP) .................................................................................... 1 
APPROVAL SHEET ...................................................................................................................... 2 
CONTRACT RESEARCH ORGANIZATION (CRO) REVIEW SHEET .................................... 3 
LIST OF ABBREVIATIONS ......................................................................................................... 4 
CONTENTS .................................................................................................................................... 6 
List of Tables .................................................................................................................................. 9 
List of Figures ................................................................................................................................. 9 
1 
INTRODUCTION ............................................................................................................ 10 
2 
STUDY OVERVIEW ....................................................................................................... 10 
2.1 
Overall Design .................................................................................................................. 10 
3 
STUDY OBJECTIVES ..................................................................................................... 11 
3.1 
Primary Efficacy Objective............................................................................................... 11 
3.2 
Secondary Objective ......................................................................................................... 11 
3.3 
Safety Objective ................................................................................................................ 11 
3.4 
Pharmacokinetic Objective ............................................................................................... 11 
4 
STUDY ENDPOINTS ...................................................................................................... 11 
4.1 
Primary Efficacy Endpoint ............................................................................................... 11 
4.2 
Secondary Efficacy Endpoints .......................................................................................... 12 
4.3 
Exploratory Endpoints ...................................................................................................... 12 
4.4 
Safety Endpoints ............................................................................................................... 12 
4.5 
Pharmacokinetics Endpoint .............................................................................................. 12 
5 
SAMPLE SIZE CONSIDERATIONS .............................................................................. 13 
6 
ANALYSIS POPULATIONS .......................................................................................... 13 
6.1 
All Enrolled Population .................................................................................................... 13 
6.2 
Safety Population .............................................................................................................. 13 
6.3 
Intent-To-Treat (ITT) Population ..................................................................................... 13 
6.4 
Efficacy Evaluable (EE) Population ................................................................................. 14 
6.5 
Pharmacokinetic (PK) Analysis Population...................................................................... 14 


  
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7 
DEFINITIONS, COMPUTATIONS AND CONVENTIONS ......................................... 14 
7.1 
Definitions......................................................................................................................... 14 
7.2 
Reporting Conventions ..................................................................................................... 14 
7.3 
Conventions for Dates....................................................................................................... 15 
7.4 
Treatment Group Presentation .......................................................................................... 16 
7.5 
Handling of Missing Data ................................................................................................. 16 
7.6 
Analysis Visit Windows ................................................................................................... 16 
8 
TIMING OF ANALYSES ................................................................................................ 17 
8.1 
Interim Analysis ................................................................................................................ 17 
8.2 
Final Analyses and Reporting ........................................................................................... 17 
9 
STATISTICAL METHODS ............................................................................................. 17 
9.1 
General Statistical Consideration ...................................................................................... 17 
9.2 
Patient Disposition ............................................................................................................ 17 
9.3 
Protocol Deviations ........................................................................................................... 17 
9.4 
Demographic and Baseline Characteristics ...................................................................... 18 
9.5 
Medical History ................................................................................................................ 18 
9.6 
Prior and Concomitant Medications and Subsequent Therapies ...................................... 18 
9.7 
Extent of Exposure and Study Drug Compliance ............................................................. 19 
9.8 
Efficacy Analyses ............................................................................................................. 20 
9.8.1 Multiplicity Adjustment for Efficacy Analyses .................................................... 20 
9.8.2 Primary Efficacy Analysis .................................................................................... 20 
9.8.2.1 Supportive Analyses .............................................................................. 22 
9.8.2.2 Sensitivity Analyses ............................................................................... 22 
9.8.3 Secondary Efficacy Analyses ............................................................................... 23 
9.8.3.1 Responders Achieving a ≥ 5% Body Weight Loss ................................ 23 
9.8.3.2 Waist-to-Hip Ratio ................................................................................. 24 
9.8.3.3 Homeostatic Model Assessment for Insulin Resistance ........................ 25 
9.8.4 Exploratory Analyses ............................................................................................ 25 
9.8.4.1 Adrenocorticotropic Hormone ............................................................... 25 


  
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9.8.4.2 Serum Cortisol ....................................................................................... 25 
9.8.4.3 Brief Psychiatric Rating Scale ............................................................... 26 
9.8.4.4 Columbia-Suicide Severity Rating Scale ............................................... 26 
9.8.4.5 Clinical Global Impression-Severity...................................................... 27 
9.8.4.6 Clinical Global Impression-Improvement ............................................. 27 
9.8.4.7 Montgomery-Asberg Depression Rating Scale ..................................... 28 
9.8.4.8 Young Mania Rating Scale .................................................................... 29 
9.8.4.9 HbA1c in Patients with Diabetes ........................................................... 29 
9.8.4.10 Fasting Plasma Glucose in Patients with Diabetes ................................ 29 
9.8.4.11 Blood Pressure in Patients with High Blood Pressure ........................... 30 
9.9 
Safety Analyses ................................................................................................................. 30 
9.9.1 Adverse Events ..................................................................................................... 30 
9.9.2 Deaths ................................................................................................................... 31 
9.9.3 Clinical Laboratory Tests ...................................................................................... 31 
9.9.4 Vital Signs ............................................................................................................. 32 
9.9.5 Electrocardiograms ............................................................................................... 32 
9.9.6 Physical Examination............................................................................................ 32 
9.9.7 Pregnancy Tests .................................................................................................... 32 
9.10 
Subgroup Analyses ........................................................................................................... 33 
9.11 
Other Exploratory Analyses .............................................................................................. 33 
9.11.1 Responders Achieving a ≥ 7% and ≥ 10% Body Weight Loss ............................. 33 
9.11.2 Fasting Lipids........................................................................................................ 33 
9.12 
COVID-19 Infection ......................................................................................................... 33 
9.13 
Pharmacokinetic Analyses ................................................................................................ 34 
10 
CHANGES FROM PROTOCOL IN STUDY CONDUCT OR STATISTICAL 
ANALYSIS PLAN ........................................................................................................... 34 
11 
REFERENCES ................................................................................................................. 34 
12 
APPENDIX ....................................................................................................................... 36 
12.1 
Imputation of Missing/Partially Missing Dates ................................................................ 36 
12.2 
Sample SAS Code ............................................................................................................. 37 


  
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List of Tables 
Table 1 
Analysis Visit Windows for Assessments .............................................................16 
Table 2 
List of statistical analyses of the primary endpoint ...............................................23 
 
List of Figures 
Figure 1 
CORT118335-876 Study Design ...........................................................................11 
 
 
 


  
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1 
INTRODUCTION 
This statistical analysis plan (SAP) contains definitions of analysis populations and endpoints, 
outlines the timing of statistical analyses, and provides a comprehensive description of statistical 
analyses to be implemented to assess the clinical efficacy and safety of protocol 
CORT118335-876, amendment 5, dated January 11, 2022: A Phase 2, Randomized, Double-
Blind, Placebo-Controlled Study Evaluating the Safety, Efficacy, and Pharmacokinetics (PK) of 
Miricorilant (CORT118335) in Obese Adult Patients with Schizophrenia or Bipolar Disorder and 
Recent Weight Gain While Taking Antipsychotic Medications (GRATITUDE). 
This SAP will be finalized before database lock and prior to data analysis to provide full details 
of statistical analysis to be presented in the clinical study report (CSR). Any changes between the 
statistical methods provided in the CSR and this SAP will be explained herein; any changes or 
deviations from this SAP relative to the final analysis will be fully documented in the CSR. 
Minor changes or deviations from the templates for tables, figures, and listings need not be 
documented in the CSR.  
2 
STUDY OVERVIEW 
2.1 
Overall Design 
This is a Phase 2, randomized, double-blind, placebo-controlled multicenter study to evaluate the 
safety, efficacy, and PK of miricorilant in obese patients (BMI ≥30 kg/m2) with schizophrenia or 
bipolar disorder who have recent antipsychotic-induced weight gain (AIWG) caused by any oral 
or injectable second-generation antipsychotic medication (except clozapine) within the last 18 
months prior to Screening. 
The study consists of the following study periods: 
• Screening Period: up to 28 days 
• Treatment Period: Day 1 to Week 12 
• Follow-up Period: 4 weeks after last study dose (Week 16) 
Patients who are eligible for participation in the study will be randomized on Day 1 in a 1:1 ratio 
to 600 mg miricorilant or placebo.  
Patients will be asked to volunteer for the PK substudy, and up to 45 patients are expected to 
provide PK samples as part of this substudy. The PK substudy will be conducted at the Week 4 
visit. In those patients who consent to participate in the substudy, blood samples will be collected 
according to the PK plan outlined in the study manual. 
An Independent Data Monitoring Committee (IDMC) will monitor safety during the study on a 
regular basis. The committee will operate independently from the sponsor and the investigators 
as described in the IDMC charter.   
 


  
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Figure 1 
CORT118335-876 Study Design 
 
Abbreviation: W, week. 
 
3 
STUDY OBJECTIVES 
3.1 
Primary Efficacy Objective 
To assess the efficacy of miricorilant compared with placebo in reversing recent AIWG caused 
by an atypical antipsychotic medication. 
3.2 
Secondary Objective 
To assess the efficacy of miricorilant in improving metabolic parameters associated with diabetes 
or cardiovascular morbidity. 
3.3 
Safety Objective 
To assess the safety of miricorilant with concurrent administration of an atypical antipsychotic 
medication. 
3.4 
Pharmacokinetic Objective 
To assess the PK of miricorilant in patients with recent AIWG caused by an atypical 
antipsychotic medication. 
4 
STUDY ENDPOINTS 
4.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the change from baseline in body weight at Week 12 for 600 
mg miricorilant versus (vs) placebo.   


  
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4.2 
Secondary Efficacy Endpoints 
The efficacy of 600 mg miricorilant vs placebo in improving metabolic parameters will be 
measured by 
• Percentage of patients achieving a ≥ 5% body weight loss from baseline at Week 12  
• Change from baseline in waist-to-hip ratio at Week 12  
• Change from baseline in Homeostatic Model Assessment for Insulin Resistance 
(HOMA-IR) at Week 12  
4.3 
Exploratory Endpoints 
Exploratory endpoints are listed by associated population.  
In all patients: 
• Change from baseline in adrenocorticotropic hormone (ACTH) at Week 12, and 
• Change from baseline in serum cortisol at Week 12. 
In patients with schizophrenia: 
• Changes from baseline in Brief Psychiatric Rating Scale (BPRS), Columbia-Suicide 
Severity Rating Scale (C-SSRS), and Clinical Global Impression scale (CGI) at 
Week 12.  
In patients with bipolar disorder: 
• Changes from baseline in C-SSRS, CGI, Young Mania Rating Scale (YMRS), and the 
Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12. 
In patients with diabetes:  
• Change from baseline in glycated hemoglobin (HbA1c) at Week 12, and 
• Change in fasting plasma glucose at Week 12. 
In patients with high blood pressure: 
• Change from baseline in blood pressure measurements at Week 12. 
4.4 
Safety Endpoints 
Safety endpoints consist of the incidence of adverse events (AEs), treatment-emergent adverse 
events (TEAEs), serious TEAEs, and AEs leading to early discontinuation.  Furthermore, safety 
endpoints include the change from baseline in clinical laboratory tests, physical examinations, 
vital sign measurements and electrocardiogram (ECG) parameters at Week 12. 
4.5 
Pharmacokinetics Endpoint 
PK assessments will be summarized in the PK/pharmacodynamic (PD) SAP. 


  
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5 
SAMPLE SIZE CONSIDERATIONS 
Approximately 70 patients will be randomized 1:1 to treatment or placebo in this study. This 
sample size provides 90% power to detect a difference in body weight change of 4 kg between 
the 600 mg miricorilant dose group and the placebo group. Based on Larsen et al. 2017, which 
examined the effect of liraglutide on olanzapine-and clozapine-treated patients, as well as on 
other studies of AIWG summarized in Mizuno et al. 2014, a standard deviation (SD) of around 
4 to 5 kg can be expected for the difference in body weight change between treatment groups. 
Accordingly, a SD of 4.5 kg is assumed here. Assuming a difference in body weight change 
between groups of 4 kg with an SD of 4.5 kg, and setting α=0.05, 28 patients per group provides 
90% power to detect a significant difference between active dose group and placebo after 
completing 12 weeks of treatment.  
Allowing for 20% dropouts increases the required sample size to 35 patients per group for a total 
of 70 patients in the trial. 
With 35 patients receiving 600 mg miricorilant in the trial, there is an 83% chance that an 
uncommon AE (i.e., an AE expected to occur in only 1 in every 20 patients) will be observed at 
least once during the trial. If a specific AE is never seen in the trial, the 95% upper confidence 
bound on its true incidence would be 10%. 
Randomization will be stratified by the type of antipsychotic medication used (olanzapine, 
risperidone/paliperidone, quetiapine, aripiprazole, or other). If at least 14 patients complete 12 
weeks of treatment (7 patients treated with 600 mg miricorilant and 7 patients treated with 
placebo) in one of the allowed antipsychotic medications, this sample size provides 50% power 
to detect a difference in body weight change of 4 kg between 600 mg miricorilant and placebo, at 
alpha=0.1 level for that stratum of antipsychotic medication. 
6 
ANALYSIS POPULATIONS 
6.1 
All Enrolled Population 
The All Enrolled population comprises all patients who meet study enrollment criteria.  
6.2 
Safety Population 
The Safety population comprises all patients who receive at least 1 dose of study drug. Safety 
data such as AEs will be summarized on the safety population.  
6.3 
Intent-To-Treat (ITT) Population 
The ITT population comprises all patients who receive at least 1 dose of study drug. The ITT 
contains the same patients as the safety population but will be referred to in sensitivity analyses 
of selected efficacy endpoints.  


  
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6.4 
Efficacy Evaluable (EE) Population 
All patients who receive ≥4 weeks of study drug and have baseline and at least 1 body weight 
measurement taken on or after Week 4. Efficacy analyses, including the primary analysis will be 
performed on the EE population. 
≥4 weeks of study drug is defined as study drug duration ≥23 days per Section 7.6. See 
Section 9.7 for calculation of study drug duration. 
6.5 
Pharmacokinetic (PK) Analysis Population 
The PK population comprises all patients who have evaluable PK data. 
7 
DEFINITIONS, COMPUTATIONS AND CONVENTIONS 
The statistical principles applied in the design and planned analyses of this study are consistent 
with International Council for Harmonisation (ICH) E9 guidelines (ICH 1998). All statistical 
analyses detailed in this SAP will be conducted using SAS version 9.4 or higher. 
7.1 
Definitions 
Last dose date will be the last documented dose date. 
Study day for efficacy will be calculated in reference to the date of first dose of miricorilant or 
placebo (Study Day 1).  For assessments conducted on or after the first dose date, study day is 
calculated as (assessment date − first dose date + 1).  For assessments conducted before the first 
dose date, study day is calculated as (assessment date − first dose date date).  There is no study 
day 0.  
Treatment-emergent period: The treatment-emergent period is defined as the period from the 
date and time of the first dose of study drug through 28 days after the last dose of study drug.  
The treatment-emergent period will be used in the summaries of TEAEs. 
Baseline will be the assessment on the Day 1 visit if non-missing, or the last non-missing 
assessment prior to first dose of study drug if Day 1 visit is missing. 
7.2 
Reporting Conventions 
Unless otherwise specified, the following conventions will be applied to all analyses:  
• Mean, median, first quartile, and third quartile values will be formatted to 1 more decimal 
place than the measured value. SD values will be formatted to 2 more decimal places than 
the measured value; minimum and maximum values will be presented to the same 
number of decimal places as the measured value.  
• Percentages will be rounded to 1 decimal place. Number and percentage values will be 
presented as xx (xx.x%). 
• Listings will be sorted for presentation in order of patient identifier (ID) and date of 
procedure or event.  


  
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• Analysis and summary tables will have the analysis population sample size (i.e., number 
of patients).  
• Laboratory data will be reported using Système International (SI) units with the exception 
of HbA1c, which will be reported using %. 
• Odds ratios will be rounded to 2 decimal places.  
• For by-visit observed data analyses, percentages will be calculated based on the number 
of patients with nonmissing data as the denominator unless otherwise specified.  
• For other continuous endpoints, the summary statistics will include mean, SD, median, 
first quartile, third quartile, and range (minimum and maximum).  
• For categorical endpoints, the summary statistics will include frequency counts and 
percentages.  
• Confidence intervals (CIs), when presented, will generally be constructed at the 95% 
level. For binomial variables, exact methods will be employed unless otherwise specified.  
• P-values will be rounded to 4 decimal places. P-values that round to 0.0000 will be 
presented as ‘<.0001’ and p-values that round to 1.000 will be presented as ‘1.000’.  
• Medical history and AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA v 23.0. AE severity will be evaluated using the National Cancer 
Institute Common Terminology Criteria for Adverse Events (CTCAE v.5.0).  
• Prior therapies and concomitant medications will be coded using the World Health 
Organization (WHO) Drug Dictionary Global B3 (September 2019) version and 
summarized by Anatomical Therapeutic Chemical (ATC) therapeutic subgroup and 
preferred drug names.  
• For continuous values (clinical laboratory values) that are not able to be determined due 
to being less than the lower limit of quantification (LLOQ) or higher than the upper limit 
of quantification (ULOQ), the value will be assigned to one unit lower than the LLOQ or 
one unit higher than the ULOQ for any analyses performed.  The original value will be 
displayed in any listings provided. 
7.3 
Conventions for Dates 
Conventions for calculations with dates are as follows:  
• Dates will be stored as numeric variables in the SAS analysis files and reported in 
DDMMMYYYY format (i.e., the Date9. date format in SAS).  
• Dates recorded in comment fields will not be imputed or reported in any specific format.  
• Intervals that are presented in weeks, months, or years will be transformed from days by 
using the following conversion formula, and rounding to 1 decimal place:  
o WEEKS = DAYS / 7  
o MONTHS = DAYS / 30.4375  
o YEARS = DAYS / 365.25 
Detailed rules for imputation of missing/partially missing dates for AEs, prior/concomitant 
medications/procedures, and schizophrenia or bipolar disorder diagnosis are provided in 
Section 12.1. 


  
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7.4 
Treatment Group Presentation 
Patient disposition, protocol deviations, demographics and baseline characteristics, medical 
history, prior medications and procedures, and efficacy data summaries will be presented by 
randomized treatment group. Unless otherwise specified, safety data summaries will be 
presented by the actual treatment received. 
7.5 
Handling of Missing Data 
Unless stated otherwise, missing data will not be replaced with imputed values.   
Missing dates or partially missing dates will be imputed conservatively for AEs and 
prior/concomitant medications/procedures. Specific rules for handling of missing or partially 
missing dates for date of birth, AEs, prior/concomitant medications/procedures, and diagnosis of 
schizophrenia or bipolar disorder are provided in Section 12.1. 
7.6 
Analysis Visit Windows 
In analyses of data summarized by study visit, if a scheduled visit is missing then unscheduled, 
early termination, and follow-up visits will be reassigned a study visit where data is scheduled 
for collection based on the actual days relative to baseline (Table 1).  If multiple visits fall in the 
analysis visit window the one closest to the target day will be used.  If two visits are equidistant 
to the target day, then the later visit will be used. 
Table 1 
Analysis Visit Windows for Assessments 
Visit Name 
Start Day 
Target Day 
End Day 
Screening 
Date of informed consent 
-28 
-1 
Baseline 
— 
1 
— 
Week 1 
2 
8 
11 
Week 2 
12 
15 
22 
Week 4 
23 
29 
36 
Week 6 
37 
43 
50 
Week 8 
51 
57 
64 
Week 10 
65 
71 
78 
Week 12 
79 
85 
92 
Follow-up 
> Study day of last dose 
of study drug  
Study day of last dose 
of study drug +28 
-  
Note: Any unscheduled, early termination or follow-up visits will be assigned to a Baseline – Week 12 analysis 
visit as priority if it fits within the window, regardless of whether the visit was after last dose of study drug. 
Otherwise, it will be considered for the follow-up analysis visit. 


  
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8 
TIMING OF ANALYSES 
8.1 
Interim Analysis  
No interim analyses are planned for this study. 
8.2 
Final Analyses and Reporting 
All planned analyses described in the SAP will be performed after the last patient has completed 
the study, all outstanding queries resolved, and the database has been locked.  
9 
STATISTICAL METHODS 
9.1 
General Statistical Consideration 
Statistical analyses will be reported with tables, figures, and listings, presented in rich text 
format, and using recommended ICH numbering. Output specifications for all tables, figures, and 
listings will be in conformance with guidelines specified by the ICH of the Electronic Common 
Technical Document Specification (Apr 2003).  
All efficacy summaries will be presented by treatment group as randomized. All safety 
summaries will be presented by actual treatment group. In addition, data will be tabulated for all 
patients combined. All relevant data collected on the electronic case report form (eCRF) will be 
presented in by-patient data listings, to include the site identifier, patient number, and assigned 
treatment group. 
In general, continuous variables will be summarized by the number of patients with non-missing 
data, mean, SD, median, minimum, and maximum values. Categorical variables will be 
summarized by the number and percentage of patients in each category. 
9.2 
Patient Disposition 
Participant disposition will show the number of patients who have been enrolled, in All Enrolled, 
Safety, ITT and EE analysis population, took study drug, discontinued treatment, discontinued 
treatment but continued with remaining scheduled visits, discontinued from the study, reasons 
for discontinuations (including if due to Coronavirus disease 2019 [COVID-19]), completed 
12 weeks of study treatment, completed the study, and completed the follow-up study visit. 
Completion of the follow-up study visit is defined as completing the date of visit eCRF for the 
follow-up visit.  
9.3 
Protocol Deviations 
Protocol deviations will be categorized as important or other according to the protocol deviation 
specification document. Important protocol deviations that occur during the study will be 
summarized by deviation category for all patients in the ITT population by treatment group as 
randomized. A by-patient listing of important protocol deviations will be provided. 


  
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Patient eligibility including inclusion and exclusion criteria that were not met at randomization 
will be summarized for all patients in the ITT population. 
9.4 
Demographic and Baseline Characteristics 
The following demographic characteristics will be presented for the All Enrolled populations in 
listings, and summarized by treatment and overall in All Enrolled, Safety and EE populations: 
• Age at informed consent (continuous and categorical variable: ≥18 to <30, ≥30 to <50, 
≥50 to ≤65) will be summarized 
• Sex  
• Of childbearing potential (Yes/No) 
• Ethnicity 
• Race 
Additionally, baseline characteristics including height, body weight, body mass index (BMI), 
BMI category (obesity class 1 (30-34.9 kg/m2), obesity class 2 (35-39.9 kg/m2), extreme obesity 
class 3 (≥ 40 kg/m2), time on current antipsychotic medication (months), antipsychotic 
medication used (olanzapine, risperidone/paliperidone, quetiapine, aripiprazole, or other), 
HOMA-IR score, ACTH, serum cortisol, BPRS, C-SSRS, CGI-S, MADRS, YMRS, time from 
schizophrenia diagnosis to enrollment (years), time from bipolar disorder diagnosis to enrollment 
(years), and waist-to-hip ratio will be summarized. BMI will be calculated as: body weight (kg) / 
[height (cm) / 100]2. Time (years) since diagnosis will be calculated as (the randomization date − 
the diagnosis date + 1)/365.25. The imputation rules for missing or partial diagnosis dates are 
described in Section 12.1. 
The demographic and baseline characteristics will also be summarized separately for patients 
diagnosed with schizophrenia or bipolar disorder using the Safety population.  Only those 
measurements associated with the given disorder will be presented. 
9.5 
Medical History 
Medical history will be summarized for all patients in the All Enrolled and Safety population. 
Frequency counts and percentages to summarize patients reporting medical history by system 
organ class (SOC) (coded using MedDRA version 23.0).   
Schizophrenia and bipolar disorder medical history will be presented separately.   
9.6 
Prior and Concomitant Medications and Subsequent Therapies 
Medications will be coded using the WHO Drug Global B3 version March 2020 or above. 
Medications entered on the eCRF will be mapped to ATC drug class (level 4) and generic drug 
name.  
A prior medication is defined as any medication administered prior to the date of the first dose of 
study drug. A concomitant medication is defined as any medication administered on or after the 
date of the first dose of study drug and up to and including the last dose date. Medications newly 


  
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administered after the last dose date are defined as subsequent therapies. A medication may be 
defined as more than one medication classification (prior, concomitant, or subsequent). The 
imputation rules for missing start and end date of a concomitant medication are described in 
Section 12.1. 
The proportion of patients who received prior, concomitant, and subsequent therapies or 
medications will be summarized separately for the Safety population. For all table summaries, 
the number and percentage of patients receiving any medication will be summarized by 
treatment group and overall. The preferred drug name and the preferred drug name within ATC 
drug class will be summarized separately and displayed by alphabetical order of ATC and 
descending order of incidence for the preferred drug name within ATC. Patients reporting use of 
more than one medication at each level of summarization (any medication received, ATC class, 
and preferred drug name) will be counted only once. The medication classification (e.g., prior, 
concomitant, subsequent, or a combination of classification) will be presented on the listing of 
prior, concomitant, and subsequent medications. 
Additionally, for patients who have diabetes at baseline, prior, concomitant, and subsequent 
medications related to diabetes will be listed. Similarly, for patients with high blood pressure at 
baseline as defined in Section 9.8.4.11, prior, concomitant, and subsequent antihypertensive 
medications will be listed.    
9.7 
Extent of Exposure and Study Drug Compliance 
All recorded information on oral dosing of miricorilant and placebo, including kit number, actual 
dose, start and end date, any dose modifications and related reason will be presented in a data 
listing sorted by start date of administration. 
A table by treatment arm and overall will provide summary statistics on the following: 
• Duration of Exposure: The duration of exposure for each study drug will be presented in 
days and calculated as: 
Duration = date of last dose − Date of the first dose + 1. 
• Total Tablets Received: The total tablets received for each study drug will be:  
Total Tablets Received = Total tablets dispensed – Total tablets returned. 
• Total Tablets Expected: A patient will have an expected number of tablets determined by 
the earliest start date and the latest end date times six tablets taken daily. For patients 
where their dose received is either zero or missing, an associated expected dose is 
included in the total dose expected derivation.  Therefore, the total dose expected to be 
taken is: 
Total Tablets Expected = Duration of Exposure × 6. 
• Compliance: Compliance is calculated for each study drug as: 
Compliance = (Total Tablets Received / Total Tablets Expected) × 100. 


  
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A by-patient listing including the study drug start date, study drug end date, number of tablets 
taken, number of tablets expected to be taken, and overall compliance will be produced.   
9.8 
Efficacy Analyses 
9.8.1 
Multiplicity Adjustment for Efficacy Analyses 
Each efficacy endpoint will be evaluated at the 2-sided 0.05 level of significance without 
adjustment for multiplicity of testing. P-values from secondary and exploratory tests will be 
considered descriptive.   
9.8.2 
Primary Efficacy Analysis 
The primary endpoint is used to evaluate the primary objective of assessing the efficacy of 
miricorilant compared with placebo in reversing AIWG caused by an atypical antipsychotic 
medication. 
The primary endpoint will be assessed using a mixed-effect model with repeated measures 
(MMRM). An MMRM analysis refers to a restricted maximum likelihood (REML)-based, 
mixed-effects repeated measures analysis using all longitudinal observations at baseline and each 
scheduled post-baseline visit. That is the change in body weight at baseline and each post-
baseline visit will be assessed using an MMRM model with baseline body weight as a 
continuous covariate; antipsychotic medication (olanzapine, risperidone/paliperidone, quetiapine, 
aripiprazole, or other), randomized treatment (600 mg miricorilant or placebo), visit, and 
treatment-by-visit interaction as fixed, categorical effects. The difference in body weight change 
between miricorilant and placebo will be estimated from the model along with its 95% CI. The 
primary analysis will be performed on the EE population. 
In more detail, the baseline body weight is reported in kg and measured at the day 1 (baseline) 
visit and at 7 post-baseline visits: Weeks 1, 2, 4, 6, 8, 10, and 12. If the body weight from the day 
1 visit is missing, then the body weight from the last non-missing assessment prior to the first 
dose of study drug will be used for the baseline body weight. For each patient, the outcome 
variable for the MMRM is the arithmetic difference between the baseline body weight and 
baseline body weight and the body weight at each post-baseline visit. Specifically, the outcome 
variable, 𝑌𝑌𝑘𝑘𝑘𝑘, at visit 𝑘𝑘, 𝑘𝑘= 1, … , 8, for the lth patient is  
𝑌𝑌𝑘𝑘𝑘𝑘= 𝑊𝑊𝑘𝑘𝑘𝑘−𝑊𝑊𝑏𝑏𝑘𝑘 
where 𝑊𝑊𝑘𝑘𝑘𝑘 is the body weight measured at visit k for the lth patient, where k =1 is the baseline 
visit, and 𝑊𝑊𝑏𝑏𝑘𝑘 is the baseline body weight for the lth patient. 
A retrieved dropout approach will be used to provide outcome measurements for patients who 
discontinue treatment prematurely. Specifically, patients will be asked to continue the study 
visits and assessments after discontinuation of study medication. Patients who return for weight 
measurements after the discontinuation of study medication will be referred to as ‘retrieved 
dropouts’. 


  
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For patients who discontinue early and do not return for weight measurements, the body weight 
from the early termination visit, follow-up visit or an unscheduled visit, if available, will be 
mapped to the analysis visit window as outlined in Section 7.6, and will be used in analysis. 
For patients who discontinue treatment earlier than Week 12, do not have weight measurements 
available after treatment discontinuation, and therefore have missing data (“non retrieved 
dropouts”), no imputations will be used. The missing at random (MAR) assumption is implied. 
The expected value of the primary analysis model can be written 
𝐸𝐸ൣ𝑌𝑌𝑖𝑖𝑖𝑖𝑘𝑘𝑘𝑘൧= 𝜇𝜇+ 𝛼𝛼𝑊𝑊𝑏𝑏𝑘𝑘+ 𝛽𝛽𝑖𝑖+ 𝛾𝛾𝑖𝑖+ 𝛿𝛿𝑘𝑘+ (𝛾𝛾𝛿𝛿)𝑖𝑖𝑘𝑘 
where 
• 𝜇𝜇 is the overall mean 
• 𝛼𝛼 is the effect of body weight at baseline 
• 𝛽𝛽𝑖𝑖, 𝑖𝑖= 1,2,3,4,5 is the effect of background antipsychotic medication (olanzapine, 
risperidone/paliperidone, quetiapine, aripiprazole, or other) 
• 𝛾𝛾𝑖𝑖, 𝑗𝑗= 1,2, is the effect of randomized treatment (placebo or 600 mg miricorilant, 
respectively) 
• 𝛿𝛿𝑘𝑘, 𝑘𝑘= 1, … , 8 is the effect of visit k 
• (𝛾𝛾𝛿𝛿)𝑖𝑖𝑘𝑘, 𝑗𝑗= 1,2; 𝑘𝑘= 1, … , 8, is the interaction between treatment j and visit k.  
The primary hypothesis tests whether there is a difference in change body weight change at 
Week 12 between miricorilant and placebo: 
𝐻𝐻0: 𝛾𝛾1 + (𝛾𝛾𝛿𝛿)1,8 − ൫𝛾𝛾2 + (𝛾𝛾𝛿𝛿)2,8൯= 0  
𝐻𝐻1: 𝛾𝛾1 + (𝛾𝛾𝛿𝛿)1,8 − ൫𝛾𝛾2 + (𝛾𝛾𝛿𝛿)2,8൯ ≠0. 
The analysis will be performed using SAS PROC MIXED (Section 12.2). REML will be used to 
fit the model. An unstructured covariance structure will be used to model the within-patient 
errors. The Kenward-Roger approximation will be used to estimate degrees of freedom.  
The primary hypothesis will be assessed using a linear contrast to estimate the difference in body 
weight change at Week 12 between miricorilant and placebo along with its 95% CI. The 
estimated difference, its 95% CI, and its associated p-value will be presented. Sample SAS code 
to implement the model is provided in Section 12.2. 
If the model does not converge with both the Hessian and the G matrix being positive definite 
under the default fitting algorithm used by PROC MIXED, the Fisher scoring algorithm will be 
implemented by specifying the SCORING option in SAS. If the model still does not converge, 
the following covariance structures will be used until the convergence criteria is met, in this 
order: Toeplitz (TOEP), first-order autoregressive [AR(1)], heterogeneous compound symmetry 
(CSH), and compound symmetry (CS). Both the Toeplitz and autoregressive structures assume 
that observations on the same patient are more closely related when they are closer in time. The 
autoregressive structure is a special case of the Toeplitz structure that requires fewer parameters 


  
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to be estimated. The compound symmetry assumes the variances are homogeneous. There is a 
correlation between two separate measurements, but it is assumed that the correlation is constant 
regardless of how far apart the measurements are. 
The least squares mean and 95% CI of the change from baseline at Week 12 will also be 
estimated from the model for each treatment group. No adjustment for multiplicity will be 
applied. 
9.8.2.1 
Supportive Analyses 
The primary analysis model (Section 9.8.2) will also be used to estimate the difference between 
treatment groups at baseline and each of other 6 post-baseline visits from Week 1 through Week 
10. The comparisons will be specified using linear contrasts analogous to that used to compare 
treatment groups at Week 12. The estimated difference between groups, its 95% CI, and its 
associated p-value will be presented for each visit. No adjustments will be made for multiplicity. 
In addition to model estimates, descriptive statistics will summarize body weight at each visit by 
treatment group, and body weight change and percent body weight change group at each post-
baseline visit. Statistics for any visit will be calculated from all patients who had body weight 
measurements at the visit. The full set of descriptive statistics will be presented tabularly and a 
subset will also be graphed. Specifically, the mean body weight change per treatment group and 
95% CI from MMRM will be graphed with time in weeks on the x axis and change in body 
weight from MMRM on the y-axis. A similar graph of the mean body weight per treatment 
group over time will be produced with 95% CI (sourced from the t-distribution).  Additionally, 
mean percent change from baseline in body weight will be presented graphically along with 
95% CI (sourced from the t-distribution) for each treatment group and visit. 
9.8.2.2 
Sensitivity Analyses 
The primary analysis uses all data observed (including data from retrieved dropouts) and a MAR 
assumption for non-retrieved dropouts (the patients with missing body weight at Week 12). 
Retrieved dropouts are patients who discontinue study treatment before Week 12 and return for 
measurement of body weight at the time of the pre-scheduled visit up to Week 12. Non-retrieved 
dropouts are patients who discontinue study treatment before Week 12 and do not return for the 
measurement of body weight after study discontinuation. 
As a sensitivity analysis, the primary analysis model as described in Section 9.8.2 will also be 
performed in ITT population. Like the primary analysis, this sensitivity analysis will use 
supplied retrieved dropout data without imputation at Week 12. 
A second sensitivity analysis will rerun the primary analysis model as described in Section 9.8.2, 
without using retrieved dropout data. Weight measurements will be considered MAR for any 
visit after a patient discontinues treatment. 
Moreover, for patients who do not have body weight at Week 12 (non-retrieved dropouts), their 
change in body weight from Baseline to Week 12 will be imputed with the treatment group mean 
change in body weight from Baseline to Week 12, derived from retrieved dropouts (the patients 




  
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As with the primary analysis, a retrieved dropout approach will be used for patients who 
discontinue treatment prior to their Week 12 visit. Those patients will be asked to return for their 
Week 12 visits, and the body weight measurement at that visit will be used to calculate the 
percent change from baseline. 
For patients who discontinue early and do not supply retrieved dropout data, the body weight 
from the early termination visit, follow-up visit or an unscheduled visit, if available and within 
the analysis visit window of Week 12 as outlined in Section 7.6, will be assigned for the body 
weight measured at Week 12 when calculating the percent change in body weight. Otherwise, the 
last available body weight measurement will be substituted for the body weight measured at 
Week 12. This is equivalent to a last observation carried forward (LOCF) approach. 
A logistic regression model with baseline value as a continuous covariate, and background 
antipsychotic medication and treatment group as factors will be used to compare miricorilant to 
placebo. The analysis will be performed on the EE population. 
A sample of SAS code that can be used to implement the logistic regression model is provided 
in Section 12.2. The p-value comparing treatment to placebo, as well as the odds ratio and its 
95% CI, will be reported from the model. 
In addition to the model results, the percentage of patients in each treatment group who lose ≥5% 
of their baseline body weight by week will be presented along with its 95% CI. The CI will be 
calculated using the Exact method. Descriptive statistics for the percent change from baseline are 
described in Section 9.8.2.1. 
9.8.3.2 
Waist-to-Hip Ratio  
The second secondary efficacy endpoint is the change from baseline in waist-to-hip ratio at 
Week 12 for 600 mg miricorilant vs placebo. The waist-to-hip ratio will be calculated as the ratio 
of the circumference of the waist to the hip. The waist-to-hip ratio will be analyzed using the 
MMRM model described in Section 9.8.2.  The difference between miricorilant and placebo at 
Week 12 will be estimated from the model along with its 95% CI and associated p-value. The 
analysis will be performed on the EE population and retrieved dropout data will be used, when 
possible, for patients who discontinue the trial early. A sample of SAS code that can be used to 
implement the MMRM model is provided in the Section 12.2. 
The same MMRM will also be used to estimate the difference between treatment groups at 
baseline and each of other 6 visits from Week 1 through Week 10. The comparisons will be 
specified using linear contrasts analogous to that used to compare treatment groups at Week 12. 
The estimated difference between groups, its 95% CI, and its associated p-value will be 
presented for each visit.  
Descriptive statistics will summarize the waist-to-hip ratio by treatment group for all visits and 
the change and percent change from baseline in waist-to-hip ratio by treatment group for all post-
baseline visit. The change from baseline in waist-to-hip ratio by treatment group and 95% CI 
from MMRM will be graphed with time in weeks on the x axis and MMRM estimated change in 
waist-to-hip ratio on the y-axis. Additionally, the mean percent change in waist-to-hip ratio at 


  
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each visit, along with 95% CI (sourced from the t-distribution), will be graphed for each 
treatment group with time in weeks on the x-axis and percent change from baseline on the y-axis. 
9.8.3.3 
Homeostatic Model Assessment for Insulin Resistance  
HOMA-IR will be calculated for each patient at Baseline and Week 12 using the approximate 
formula (Matthews et al. 1985):  
HOMA-IR = (fasting plasma glucose (mg/dL) × fasting insulin (µU/mL))/405. 
Miricorilant will be compared to placebo on the difference in HOMA-IR between Week 12 and 
baseline using a Wilcoxon rank-sum test on the EE population. For patients who discontinue 
early, HOMA-IR from the early termination visit, follow-up visit, or an unscheduled visit, if 
available and within the analysis visit window as outlined in Section 7.6, will be used in place of 
missing Week 12 results. Data for non-retrieved dropouts will not be imputed. 
Descriptive statistics will summarize HOMA-IR by treatment group for all visits and the change 
and percent change from baseline in HOMA-IR by treatment group for all post-baseline visit. 
The median percent change in HOMA-IR at each visit will be graphed as box plots for each 
treatment group with time in weeks on the x-axis and percent change from baseline on the y-axis. 
Similar plots will be generated for median change in HOMA-IR at each visit. 
9.8.4 
Exploratory Analyses 
9.8.4.1 
Adrenocorticotropic Hormone 
ACTH will be measured at baseline, Week 4, and Week 12. Miricorilant will be compared to 
placebo on the change from baseline in ACTH at Week 12 using the MMRM model described in 
Section 9.8.2. The outcome variable will be the difference between ACTH at baseline and each 
post-baseline visit and the ACTH value at baseline. Retrieved dropout data will be used for 
patients who discontinue treatment early. Data for non-retrieved dropouts will not be imputed. 
The analysis will be performed on the EE population.  
A linear contrast analogous to that used in the primary analysis will estimate the difference 
between miricorilant and placebo in the change in ACTH at Week 12. The estimated difference, 
its 95% CI, and its associated p-value will be presented. A sample of SAS code that can be used 
to implement the MMRM model is provided in the Section 12.2. 
Descriptive statistics will summarize ACTH by treatment at each visit and the change from 
baseline in ACTH by treatment at each post-baseline visit. The mean ACTH, along with its 95% 
CI from MMRM, will be graphed for each treatment group with time in weeks on the x-axis and 
change from baseline on the y-axis. 
9.8.4.2 
Serum Cortisol 
Like ACTH, serum cortisol will be measured at baseline, Week 4, and Week 12. Miricorilant 
will be compared to placebo on the change from baseline in serum at Week 12 using the same 
method and model as ACTH (Section 9.8.4.1) with only two differences: (1) baseline serum 


  
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cortisol will replace serum ACTH as a continuous covariate in the model; and (2) the outcome 
variable will be the difference between serum cortisol at baseline and each post-baseline visit and 
the serum cortisol value at baseline. Data for non-retrieved dropouts will not be imputed. 
A sample of SAS code that can be used to implement the MMRM model is provided in the 
Section 12.2.  
Descriptive statistics will summarize serum cortisol by treatment at each visit and the change 
from baseline in serum cortisol by treatment at each post-baseline visit. The mean serum cortisol, 
along with its 95% CI from MMRM, will be graphed for each treatment group with time in 
weeks on the x-axis and change from baseline on the y-axis. 
9.8.4.3 
Brief Psychiatric Rating Scale 
The BPRS is a scale used to track changes in schizophrenia symptoms over time. The scale 
involves an interview of the patient by the Investigator and includes 24 different symptom areas 
in which the Investigator ranks the severity of each symptom using a scale of 1 (symptom is 
absent) to 7 (symptom is severe). The BPRS total score is calculated by adding together the 
scores from the 24 individual symptom areas. Higher scores indicate more severe pathology. 
It will be assessed at every visit.  
The change from baseline in the BPRS total score will use the MMRM analysis as described in 
Section 9.8.2 to assess the difference between miricorilant and placebo. Baseline BPRS total 
score will be incorporated into the model as the continuous baseline covariate. The outcome 
variable will be the difference between the total BPRS score at baseline and each post-baseline 
visit and the total BPRS value at baseline. Data for non-retrieved dropouts will not be imputed. 
The analysis will be performed on the EE population for patients with schizophrenia. 
A linear contrast will estimate the difference between miricorilant and placebo in the change in 
BPRS total score at Week 12. The estimated difference, its 95% CI, and its associated p-value 
will be presented. A sample of SAS code that can be used to implement the MMRM model is 
provided in the Section 12.2. 
Descriptive statistics will summarize the BPRS total score by treatment at each visit and the 
change from baseline in BPRS total score by treatment at baseline and each post-baseline visit. 
The mean change from baseline in BPRS total score, along with its 95% CI from MMRM, will 
be graphed for each treatment group with time in weeks on the x-axis and change from baseline 
on the y-axis. 
9.8.4.4 
Columbia-Suicide Severity Rating Scale 
The C-SSRS is a suicidal ideation rating scale used to evaluate suicidality (Posner et al. 2011). 
The C-SSRS consists of a series of questions to patients that can help identify patients at risk for 
suicide, assess the severity and immediacy of that risk, and gauge the level of support the patient 
may need.  
Suicidal ideation is defined as a “yes” response to any of the five suicidal ideation questions 
(wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods 


  
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(not plan) without intent to act, active suicidal ideation with some intent to act, without specific 
plan, or active suicidal ideation with specific plan and intent). 
Suicidal behavior is defined as a “yes” response to any of the five suicidal behavior questions 
(actual attempt, interrupted attempt, aborted attempt, preparatory acts or behavior, or suicide). 
C-SSRS suicidal ideation, suicidal behavior and suicidal ideation or behavior will be 
summarized as dichotomous variables by treatment at each visit for the Safety population 
separately for patients with schizophrenia or bipolar disorder. A shift table will be provided to 
demonstrate changes in C-SSRS categories from baseline to the worst post-baseline category 
(suicidal behavior being considered worse than suicidal ideation).  
The suicidal ideation intensity rating is defined as the sum of the five intensity item scores 
(frequency, duration, controllability, deterrents, and reasons for ideation) to create a total score 
(range 0 to 25) to represent the intensity rating. If the patient did not endorse any suicidal 
ideation, set the intensity rating to 0. The suicidal ideation intensity rating score will be listed. 
9.8.4.5 
Clinical Global Impression-Severity 
The CGI, used to assess the patient’s global functioning, is comprised of two scales: the 
CGI-Severity scale (CGI-S), which assesses illness severity, and the CGI-Improvement scales 
(CGI-I), which assesses change from the initiation of treatment. The CGI-S asks the Investigator 
one question: “Considering your total clinical experience with this particular population, how 
mentally ill is the patient at this time?”, which is rated on the following 7-point scale: 1=normal, 
not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely 
ill; 7=among the most extremely ill patients.  
The numerical results from the CGI-S will be treated as a continuous variable. The MMRM 
described in Section 9.8.2 will be used to assess the difference between miricorilant and placebo 
in the change from baseline in CGI-S at Week 12. Baseline CGI-S will be incorporated into the 
model as the continuous baseline covariate. The outcome variable will be the difference between 
the CGI-S score at baseline and each post-baseline visit and the CGI-S score at baseline. Data for 
non-retrieved dropouts will not be imputed. The analysis will be performed on the EE 
population. A sample of SAS code that can be used to implement the MMRM model is provided 
in the Section 12.2.   
Descriptive statistics will summarize the CGI-S score by treatment at each visit and the change 
from baseline in CGI-S score by treatment at each post-baseline visit. 
Additionally, the MMRM analysis and descriptive statistics summary table will be presented 
separately for patients diagnosed with schizophrenia or bipolar disorder using the EE population.   
9.8.4.6 
Clinical Global Impression-Improvement 
The CGI-I comprises one question to the investigator: “Compared to the patient's condition at 
baseline, this patient’s condition is: 1=very much improved since the initiation of treatment; 
2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of 


  
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treatment); 5=minimally worse; 6=much worse; 7=very much worse since the initiation of 
treatment.” 
Note that the CGI-I inherently incorporates change from baseline into its scores. Thus, the scores 
themselves are used to evaluate change from baseline with no need to explicitly calculate the 
difference from baseline. The baseline CGI-S score is still used in the CGI-I analysis but only as 
a covariate in the analysis model. 
To assess the exploratory CGI-I endpoint, the numerical results from the CGI-I will be treated as 
a continuous variable and an MMRM similar to that described in Section 9.8.2 will be used to 
assess the difference between miricorilant and placebo at Week 12. The difference is the 
outcome variable will be the CGI-I score at each post-baseline visit. Other aspects of the model 
such as the fitting algorithm, covariance structure, and degrees of freedom are the same as for the 
primary analysis. Data for non-retrieved dropouts will not be imputed. The analysis will be 
performed on the EE population.  
Descriptive statistics will summarize the CGI-I score by treatment at each visit. Additionally, the 
MMRM analysis and descriptive statistics summary table will be presented separately for 
patients diagnosed with schizophrenia or bipolar disorder using the EE population.   
The CGI-I will also be summarized as a dichotomous variable where a positive response is 
defined as having a score of 1 (very much improved), 2 (much improved) and 3 (minimally 
improved). The number and percentage of patients with a positive response will be presented by 
treatment group for each post-baseline visit. Fisher’s exact tests will be used to compare the 
treatment groups on the percent with a positive response at each visit.  
9.8.4.7 
Montgomery-Asberg Depression Rating Scale  
The MADRS is a ten-item diagnostic questionnaire used by psychiatrists to measure the severity 
of depressive episodes in patients with mood disorders. The questionnaire includes questions on 
the following symptoms: 1) Apparent sadness 2) Reported sadness 3) Inner tension 4) Reduced 
sleep 5) Reduced appetite 6) Concentration difficulties 7) Lassitude 8) Inability to feel 9) 
Pessimistic thoughts 10) Suicidal thoughts. Each question yields a score from 0–6; higher 
MADRS score indicates more severe depression. A total MADRS score will be determined as 
the sum of the individual scores (range 0 to 60). 
The change from baseline in the MADRS score will use the MMRM analysis as described in 
Section 9.8.2 to assess the difference between miricorilant and placebo. Baseline MADRS score 
will be incorporated into the model as the continuous baseline covariate. The outcome variable 
will be the difference between the total MADRS score at baseline and each post-baseline visit 
and the total MADRS value at baseline. Data for non-retrieved dropouts will not be imputed. The 
analysis will be performed on the EE population for patients with bipolar disorder. A sample of 
SAS code that can be used to implement the MMRM model is provided in the Section 12.2.   
Descriptive statistics will summarize the MADRS score by treatment at each visit and the change 
from baseline in MADRS score by treatment at each post-baseline visit. 


  
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9.8.4.8 
Young Mania Rating Scale 
The YMRS is a clinical interview scale to assess the severity of manic states. The scale has 
eleven items and is based on the patient’s subjective report of his or her clinical condition. The 
purpose of each item is to rate the severity of that abnormality in the patient, making it useful for 
continuous evaluations of manic symptoms. It can help guide clinicians on treatment planning 
and progress. A total YMRS score will be determined as the sum of the individual scores 
(range 0 to 60). 
The change from baseline in the YMRS score will use the MMRM analysis as described in 
Section 9.8.2 to assess the difference between miricorilant and placebo. Baseline YMRS will be 
incorporated into the model as the continuous baseline covariate. The outcome variable will be 
the difference between the total YMRS score at baseline and each post-baseline visit and the 
total YMRS value at baseline. Data for non-retrieved dropouts will not be imputed. The analysis 
will be performed on the EE population for patients with bipolar disorder.  
Descriptive statistics will summarize the YMRS score by treatment at each visit and the change 
from baseline in YMRS score by treatment at each post-baseline visit. 
9.8.4.9 
HbA1c in Patients with Diabetes 
The analysis described here will be performed on the subset of patients in the EE population who 
have diabetes at baseline. Measurements of glycated hemoglobin (HbA1c) will be obtained at 
screening, baseline, and Week 12. Miricorilant will be compared to placebo on the difference in 
HbA1c between Week 12 and baseline using a Wilcoxon rank-sum test. For patients who 
discontinue early, HbA1c from the early termination visit, follow-up visit, or an unscheduled 
visit, if available and within the analysis visit window as outlined in Section 7.6, will be used in 
place of missing Week 12 results. Data for non-retrieved dropouts will not be imputed. 
Descriptive statistics will summarize HbA1c by treatment at baseline and Week 12 and the 
change from baseline in HbA1c by treatment at Week 12. 
Similarly, descriptive statistics and Wilcoxon rank-sum test will be provided separately for 
patients with an HbA1c < 6.5%, 6.5% ≤ HbA1c < 8%, and an HbA1c ≥8%  at baseline 
regardless of whether the patient has diabetes at baseline, assuming at least 10 patients per group.  
If there are less than 10 patients for a given group, then only descriptive statistics will be 
provided for that group. 
9.8.4.10 
Fasting Plasma Glucose in Patients with Diabetes 
The analysis described here is analogous to that described for HbA1c and will be performed on 
the subset of patients in the EE population who have diabetes at baseline. Fasting plasma glucose 
measurements will be obtained at baseline and Week 12. Miricorilant will be compared to 
placebo on the difference in fasting plasma glucose between Week 12 and baseline using a 
Wilcoxon rank-sum test. For patients who discontinue early, fasting plasma glucose measured at 
the early termination visit, follow-up visit or an unscheduled visit, if available and within the 


  
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analysis visit window as outlined in Section 7.6, will be used in place of missing Week 12 
results. Data for non-retrieved dropouts will not be imputed. 
Descriptive statistics will summarize fasting plasma glucose by treatment at baseline and Week 
12 and the change from baseline in fasting plasma glucose by treatment at Week 12. 
9.8.4.11 
Blood Pressure in Patients with High Blood Pressure 
The analysis described here will be performed on the subset of patients in the EE population who 
have high blood pressure at the baseline visit. High blood pressure is based on the limits for 
Stage 1 hypertension defined in the 2017 guideline developed by the American College of 
Cardiology and American Heart Association (Whelton 2017). Specifically, a patient will be 
considered to have high blood pressure if they satisfy any of the following criteria regardless of 
position (seated, supine, or standing): 
• baseline systolic blood pressure (SBP) is ≥ 130 mm Hg, 
• baseline diastolic blood pressure (DBP) ≥ 80 mm Hg, or 
• if being treated with an antihypertensive medication at baseline or has medical history of 
hypertension.  
Vital signs, including orthostatic vital signs, including SBP and DBP, will be measured at every 
visit. Descriptive statistics will summarize SBP and DBP by position (seated, supine, and 
standing) by treatment at baseline and each post-baseline visit. The difference in SBP and DBP 
at each visit and their corresponding baseline values will be calculated and summarized by 
position (seated, supine, and standing) by treatment group for each post-baseline visit. The 
significance of the difference between groups in change from baseline will be assessed using a 
pair of Wilcoxon rank-sum tests – one comparing groups on change in SBP and the second 
comparing groups on change in DBP – at each visit. 
9.9 
Safety Analyses 
All safety analyses will be performed in the Safety Population. All safety data will appear in by-
patient data listings. Unless specified otherwise, the categorical safety analyses will include both 
scheduled and unscheduled visits.  
9.9.1 
Adverse Events 
TEAEs are defined as those AEs with onset on or after the first dose of study drug or existing 
events that worsened after the first dose during the study and up to and including 28 days after 
the last dose of study drug. 
Events reported with a partial onset date (e.g., month and year are reported but the day is 
missing) will be considered to be treatment-emergent, as appropriate, if it cannot be confirmed 
that the event onset was prior to the first dose of study drug based on the available date entries. 


  
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Summaries that are displayed by SOC and preferred terms (PT) will be ordered by alphabetical 
order of SOC and by descending incidence of PT nested within each SOC. Summaries displayed 
by PT only will be ordered by descending incidence of PT.  
Tabular summaries with numbers and percentages of patients that have the following AEs will be 
provided: 
• Overview of AEs  
• Summary of TEAEs  
• Summary of TEAEs related to study drug (defined as possibly related or probably 
related) 
• Summary of TEAEs leading to dose discontinuation (i.e. study drug withdrawn) 
• Summary of TEAEs leading to dose interruption 
• Summary of serious TEAEs 
• Summary of serious TEAEs related to study drug 
• Summary of serious TEAEs leading to dose discontinuation 
• Summary of TEAEs with fatal outcome 
• Summary of TEAEs with grade 3 or higher  
• Summary of TEAEs related to study drug with grade 3 or higher  
• Summary of TEAEs of excessive glucocorticoid receptor (GR) or mineralocorticoid 
receptor (MR) antagonism (Protocol section 5.2.2) 
All above summaries will be presented by PT, and by PT nested within SOC. Also, summaries 
by maximum severity will be provided for TEAEs and serious TEAEs.   
TEAEs and serious TEAEs will also be presented by decreasing incidence of PT per 100 patient 
years of exposure, calculated as (number of subjects with events/total patient-years) × 100, 
where patient-years is the sum of exposure patient-years (days / 365.25) of all patients within the 
treatment group.  
All AEs, whether treatment-emergent or not, will be listed by individual patient and treatment 
arm, including dates of onset and resolution and associated study day, duration, serious, CTCAE 
grade, action taken, outcome, and relationship to study drug. Serious TEAEs and TEAEs leading 
to discontinuation will also be listed separately. 
9.9.2 
Deaths 
All deaths during the study, including the Follow-up period, will be listed including the primary 
cause of death.  
9.9.3 
Clinical Laboratory Tests 
All descriptive summaries of laboratory results will be based on data analyzed by the central 
laboratory and presented in SI units with the exception of HbA1c, which will be presented in 
% units. All data will be included in by-patient data listings. Laboratory measurements identified 
as abnormal (i.e., outside the normal range) will also be listed separately by patient, study visit, 


  
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laboratory test, unit laboratory value, normal ranges, and abnormal category (e.g. high, low, 
abnormal). 
Clinical laboratory measurements, including chemistry and hematology, will be summarized by 
visit. Descriptive statistics will be presented for observed values as well as change from baseline 
for all post-baseline visits for the Treatment and Follow-up periods.  Shift from baseline CTCAE 
grade to worst post-baseline grade, as well as shift from baseline abnormal category to worst 
post-baseline category will be provided. 
Additionally, a summary of the number of patients with liver test abnormalities will be provided 
for the worst value after first dose of study drug including alanine aminotransferase (ALT) 
(>3x upper limit of normal [ULN], >5xULN, >8xULN, >10xULN, and >20xULN), aspartate 
aminotransferase (AST) (>3xULN, >5xULN, >8xULN, >10xULN, and >20xULN), total 
bilirubin (>ULN and >2xULN), ALP (>1.5xULN), ALT or AST >3xULN and total bilirubin 
(>1.5xULN and >2xULN), and ALT or AST >3xULN and  international normalized ratio (INR) 
>1.5. A listing of all patients with liver test abnormalities will be provided including all 
laboratory values and corresponding abnormality. For ALT, AST, total bilirubin, alkaline 
phosphatase, and gamma-glutamyl transferase (GGT), the mean and 95% CI per treatment group 
will be graphed with time in weeks on the x axis and lab value on the y-axis. Furthermore, an 
Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) graph will be provided. 
9.9.4 
Vital Signs  
Vital sign parameter measurements, including orthostatic vital signs, including systolic and 
diastolic BP, heart rate, respiratory rate, and body temperature, will be summarized. Descriptive 
statistics will be presented by position (seated, supine, and standing) for observed values as well 
as change from baseline for all post-baseline visits for the Treatment and Follow-up periods.  
9.9.5 
Electrocardiograms 
Twelve-lead ECG interval parameters will be summarized. Descriptive statistics will be 
presented for observed values as well as change from baseline for all post-baseline visits for the 
Treatment and Follow-up periods using the average of the triplicate readings per patient per visit. 
Twelve-lead ECG results will be classified as “normal” and “abnormal.” A listing of ECG results 
will be provided including visit, date, and interpretation results. 
9.9.6 
Physical Examination 
Results of the physical examination will be presented in patient data listings by study visit and 
body system. A listing of abnormal physical exam findings by visit and body system will be 
provided. The description of the abnormal finding and indication if the finding was clinically 
significant or not will be displayed. 
9.9.7 
Pregnancy Tests 
Results of the pregnancy tests will be presented in patient data listings by study visit.  


  
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9.10 
Subgroup Analyses 
Subgroup analyses will be performed for the primary efficacy measure (mean change from 
baseline in body weight) for the EE patients for the following: 
• For the subgroup variable of antipsychotic medication (stratification factor). 
o Each subgroup will be analyzed as is. 
o We will perform an additional subgroup analysis by combining Aripiprazole, 
Quetiapine and Other. 
• For the subgroup variable of disorder diagnosis (schizophrenia or bipolar disorder).  
• For the subgroup variable of BMI group (30-34.9, 35-39.9, ≥ 40). 
Treatment group differences will be evaluated within each category of the subgroup variable.  
For all the subgroup variables, the subgroup analysis for change from baseline in body weight 
to each week will be conducted with MMRM. The same MMRM model as described in 
Section 9.8.2 will be used with terms of subgroup, subgroup-by-treatment, subgroup-by-visit, 
and subgroup-by-treatment-by-visit interactions added as factors. Data for non-retrieved 
dropouts will not be imputed. A sample of SAS code that can be used to implement the 
MMRM model is provided in the Section 12.2.   
9.11 
Other Exploratory Analyses 
Additional exploratory efficacy/safety analyses will be conducted as deemed necessary. 
9.11.1 Responders Achieving a ≥ 7% and ≥ 10% Body Weight Loss 
A responder is defined as a patient achieving ≥7% and ≥10% body weight loss, respectively, and 
will be determined as described in Section 9.8.3.1.  Similar to the secondary efficacy endpoint, 
the binary responder outcome will be analyzed using a logistic regression model as described in 
Section 9.8.3.1.  
9.11.2 Fasting Lipids 
Fasting lipids (triglycerides, low-density lipoprotein [LDL], high-density lipoprotein [HDL], 
very low-density lipoprotein [VLDL], total cholesterol) will be summarized by visit (baseline 
and Week 12) using the safety population. Descriptive statistics will be presented for observed 
values as well as change from baseline to Week 12.  
9.12 
COVID-19 Infection 
Information regarding visits that are affected by COVID-19 pandemic are being collected on the 
eCRF. A listing of visits that are affected by COVID-19 pandemic will be provided. 
Additionally, a listing of protocol deviations associated with COVID-19 and an AE listing of 
patients with a positive diagnosis of COVID-19 infection will be provided. Any additional 


  
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analyses determined to be appropriate for patients impacted by COVID-19 pandemic will be 
performed as deemed necessary.  
Summaries of protocol deviations associated with COVID-19 will be provided for all enrolled 
patients. A summary of subjects with visits affected by COVID-19 will be provided for all 
enrolled patients. 
9.13 
Pharmacokinetic Analyses 
PK endpoints and analysis methods will be described in a separate PK Analysis Plan that will be 
finalized before the database lock. 
10 
CHANGES FROM PROTOCOL IN STUDY CONDUCT OR STATISTICAL 
ANALYSIS PLAN 
The SAP supersedes the statistical methods described in the clinical study protocol. Analysis 
methods that summarize and evaluate study efficacy endpoints for statistical significance will be 
implemented as described in the SAP. 
The Protocol specifies that HOMA-IR will be analyzed using similar models as the primary 
analysis of body weight change (i.e. MMRM), and that it may be log-transformed prior to 
analysis. However, HOMA-IR is only collected at one post-baseline visit, so MMRM is not 
appropriate. Wilcoxon rank-sum test is used instead, and it is done without log-transformation of 
the data. 
Similarly for waist-to-hip ratio, the Protocol specifies that it may be log-transformed prior to 
analysis. However, the data looks reasonably symmetric, so the untransformed values will be 
used.  
11 
REFERENCES 
Larsen JR, Vedtofte L, Jakobsen MSL. 2017. Effect of liraglutide treatment on prediabetes and 
overweight or obesity in clozapine- or olanzapine-treated patients with schizophrenia 
spectrum disorder. JAMA Psychiatry 74(7):719–728. 
Mathews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner RC. 1985. Homeostasis model 
assessment: insulin resistance and beta-cell function from fasting plasma glucose and 
insulin concentrations in man. Diabetologia 28(7): 412–419. 
Mizuno Y, Suzuki T, Nakagawa A, Yoshida K, Mimura M, Fleischhacker WW, et al. 2014. 
Pharmacological strategies to counteract antipsychotic-induced weight gain and 
metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. 
Schizophr Bull. 40(6):1385–1403. 
M2 eCTD: Electronic Common Technical Document Specification Appendix 7, provided by the 
International Conference on Harmonization. Available from: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/ucm073240.pdf 


  
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Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin 
GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial 
validity and internal consistency findings from three multisite studies with adolescents 
and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. 
Whelton PK, Carey RM, Aronow WS, et al. 2017 
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the 
Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A 
Report of the American College of Cardiology/American Heart Association Task Force 
on Clinical Practice Guidelines. Hypertension. 2017. 
doi:10.1161/HYP.0000000000000065  
 


  
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12 
APPENDIX 
12.1 
Imputation of Missing/Partially Missing Dates  
For AEs with a partial date, available date parts (year, month, and day) of the partial date will be 
compared with the corresponding date components of the start date and end date of the 
treatment-emergent period to determine if the event is treatment emergent. The following rules 
will be applied to impute partial dates for AEs. 
If start date of an AE is partially missing, following imputation rules will be applied: 
• If both Month and Day are missing and Year = Year of treatment start date, then set to 
treatment start date. 
• If both Month and Day are missing and Year ≠ Year of treatment start date, then set to 
January 1. 
• If Day is missing and Month and Year = Month and Year of treatment start date, then set 
to treatment start date. 
• If Day is missing and Month and Year ≠ Month and Year of treatment start date, then set 
to first of the month. 
• If start date is completely missing, set to treatment start date as long as AE end date is not 
prior to treatment start date. 
If end date of an AE is partially missing, following imputation rules will be applied: 
• If both Month and Day are missing, then set to December 31. 
• If only Day is missing, then set to last day of the month. 
• If end date is completely missing, do not impute. 
When the start date or end date of a medication is partially missing, the date will be imputed to 
determine whether the medication is prior or concomitant (or both). The following rules will be 
applied to impute partial dates for medications: 
If start date of a medication is partially missing, following imputation rules will be applied: 
• If both Month and Day are missing, then set to January 1. 
• If only Day is missing, then set to the first. 
If end date of a medication is partially missing, following imputation rules will be applied: 
• If both Month and Day are missing, then set to December 31. 
• If only Day is missing, then set to last day of the month. 
If start date or end date of a medication is completely missing, no imputation is applied. 
When the diagnosis date of schizophrenia or bipolar disorder is missing, the following 
imputation rules will be applied: 
• If both Month and Day are missing, then set to January 1. 
• If only Day is missing, then set to the first. 


  
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12.2 
Sample SAS Code 
A sample SAS code to implement the MMRM model is as follows. The MMRM model is 
described in Section 9.8.2. The baseline covariate and outcome variable may differ for each 
analysis, refer to associated section for more details.   
proc mixed data=Data; 
  class patient antipsyc treat visit; 
  model chg = base antipsyc treat visit treat*visit /ddfm=KR; 
  repeated visit / subject=patient type=un; 
  lsmeans treat*visit /cl; *Get change lsm estimates at Wk 12; 
  estimate 'Miricorilant - Placebo at Week 12'  
    treat 1 -1  
    treat*visit 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 -1 /cl; *Get diff 
at Wk 12; 
run; 
A sample of SAS code that can be used to implement the logistic regression model is as follows. 
The code assumes the reference group, i.e., the placebo patients, comes first in the 
parameterization of the data. 
proc logistic data=WtData; 
  class antipsyc treat (ref=first) / param=glm; 
  model WtXPct (event="1") = wtbase antipsyc treat; 
  lsmeans treat / diff oddsratio cl; 
run; 
where WtXPct is the responder variable as determined in Section 9.8.3.1.