Clinical trial NCT04524403
Conditions: Antipsychotic-induced Weight Gain (AIWG)
Keywords: Antipsychotic-induced weight gain (AIWG) Obesity Weight Gain Mental disorders Schizophrenia Risperidone Paliperidone Quetiapine Olanzapine
Sponsor: Corcept Therapeutics
Start date: 2020-09-09; Completion date: 2022-08-25
Enrollment: 150 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 patients with schizophrenia 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 who are currently taking olanzapine, risperidone, paliperidone, or quetiapine.

Patients who meet the criteria for the Study CORT118335-877 will be randomized on Day 1 to receive 600 mg miricorilant, 900 mg miricorilant, or placebo for 26 weeks.

Arms: arm 1: Patients who meet the entry criteria will be randomized to receive 600 mg miricorilant for 26 weeks. arm 2: Patients who meet the entry criteria will be randomized to receive 900 mg miricorilant for 26 weeks. arm 3: Patients who meet the entry criteria will be randomized to receive placebo for 26 weeks.
Interventions: intervention 1: Miricorlilant intervention 2: Miricorlilant intervention 3: Placebo
Intervention descriptions: intervention 1: Miricorilant 600 mg (4 X 150 mg) for once-daily for oral dosing intervention 2: Miricorilant 900 mg (6 X 150 mg) for once-daily for oral dosing intervention 3: Placebo 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 in Obese Adult Patients with Schizophrenia 
Taking Antipsychotic Medications (GRATITUDE II) 
 
NCT Number: NCT04524403 
 
Date: 09 June 2022 




Protocol CORT118335-877 
Corcept Therapeutics  
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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 in Obese Adult Patients with Schizophrenia Taking 
Antipsychotic Medications (GRATITUDE II) 
Protocol Number 
CORT118335-877 
Version 
Amendment 5 
Date 
09 June 2022 
 
APPROVAL STATEMENT 
The undersigned has reviewed the format and content of the above protocol and approved 
for issuance.  
 
Signed and Dated:  
 


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PROTOCOL SYNOPSIS 
Name of Sponsor 
Corcept Therapeutics  
Name of Active Ingredient 
Miricorilant 
Study Number 
CORT118335-877  
Title of Study  
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Efficacy, and 
Pharmacokinetics of Miricorilant in Obese Adult Patients with Schizophrenia Taking Antipsychotic 
Medications (GRATITUDE II) 
Study Centers  
Approximately 35 sites in the US  
Phase of Development 
Phase 2 
Study Objectives 
Primary Efficacy 
• To assess the efficacy of both dose levels of miricorilant versus placebo in reversing 
antipsychotic-induced weight gain (AIWG). 
Secondary Efficacy 
• To assess the efficacy of both dose levels of miricorilant combined versus placebo in 
reversing AIWG.  
• To assess the efficacy of miricorilant versus placebo in improving markers of cardiovascular 
risk such as waist-to-hip ratio.  
Exploratory 
• To assess the efficacy of miricorilant versus placebo in reversing AIWG for each subgroup 
of patients taking: 
- Olanzapine 
- Risperidone or paliperidone (active risperidone metabolite) 
- Quetiapine 
• To assess the efficacy of miricorilant versus placebo in reducing insulin resistance in patients 
not treated with insulin. 
• To be assessed by patient group:  
- In all patients, change in adrenocorticotropic hormone (ACTH), serum cortisol, serum 
aldosterone, Brief Psychiatric Rating Scale (BPRS), Columbia Suicide Severity Rating 
Scale (C-SSRS), Clinical Global Impression (CGI) Scale, Obesity Weight Loss Quality 
of Life scale (OWLQOL), and Weight-Related Symptom Measure (WRSM).  
- In patients with diabetes, change in glycated hemoglobin (HbA1c) and fasting 
blood glucose. 
- In patients with high blood pressure, change in blood pressure. 
• To evaluate the dose-response relationship between miricorilant and change in body weight. 
• To evaluate the exposure-response relationship between miricorilant and change in body weight. 
Safety 
• To assess the safety of miricorilant versus placebo. 


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Pharmacokinetic (PK) 
• To assess the PK of both dose levels of miricorilant. 
Population 
Obese patients (BMI ≥30 kg/m2) with schizophrenia currently taking antipsychotic medication 
(olanzapine, risperidone, paliperidone, or quetiapine). 
Number of Patients Planned 
Approximately 150 patients will be enrolled in the study. 
Methodology 
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 currently 
taking olanzapine, risperidone, paliperidone, or quetiapine (Figure S1). 
Figure S1 
CORT118335-877 Study Design  
 
Abbreviations: PK, pharmacokinetics; W, week. 
 
Patients who are eligible for participation in the study will be randomized on Day 1 in a 1:1:1 ratio to 
600 mg miricorilant, 900 mg miricorilant, or placebo, for 26 weeks of treatment. Randomization will 
be stratified by background antipsychotic medication (3 strata: olanzapine, risperidone or paliperidone, 
or quetiapine) to ensure approximately equal numbers of patients in each stratum are assigned to the 
600 mg miricorilant, 900 mg miricorilant, and placebo groups. 
Patients will be encouraged to volunteer for the PK substudy, which will be conducted at the 
Week 4 visit. Approximately 45 patients are expected to participate. In patients who consent to 
participate, blood samples for the measurement of miricorilant plasma concentrations will be 
collected according to the PK plan. 
Duration of Treatment and Duration of Study  
The maximum expected duration of a patient’s participation is 34 weeks consisting to the following 
study periods: 
• Screening Period: Up to 28 days 
• Treatment Period: Day 1 (Baseline) to Week 26 
• Follow-up Period: 4 weeks after last dose of study drug 


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Key Inclusion Criteria 
Please see Sections 4.1 and 4.2 for a complete list of all eligibility criteria.  
Patients must meet the following criteria to be eligible for enrollment into this study: 
• Are men or women ≥18 to ≤65 years old. 
• Meet the criteria for schizophrenia based on medical history and the Mini International 
Neuropsychiatric Interview (MINI).  
• Are currently taking olanzapine, risperidone, paliperidone, or quetiapine; long-acting, injectable 
formulations of olanzapine, risperidone, and paliperidone are acceptable. 
• Have gained weight from treatment with olanzapine, risperidone, paliperidone, or quetiapine 
(patient must meet at least one criterion from each column):  
 
Self-Assessment:  
• Noticeable weight gain (~10 pounds 
or more) after initiation of 
antipsychotic medication  
Corroborated Reports:  
• Clinician or other health professional verifies 
that patient has gained weight (~10 pounds or 
more) since initiation of antipsychotic 
medication 
• 
Increase in clothing size by two size 
units (e.g., size 10 to 14) after 
initiation of antipsychotic medication 
• Caretaker or close friend/family member 
verifies that patient has gained weight 
(~10 pounds or more) since initiation of 
antipsychotic medication 
• 
Increase in pant waist size by 
4 inches (e.g., size 32 to 36) after 
initiation of antipsychotic medication  
• Hospital or medical records indicate that 
patient has gained ≥5% of baseline weight 
since initiation of antipsychotic medication 
• Have a BMI ≥30 kg/m2. 
• Have been on the same dose of antipsychotic medication for the last month prior to Screening. 
• Are clinically stable and unlikely to require change to their antipsychotic medication (i.e., switch 
medication or change dose) through the duration of the study (34 weeks). 
• Have a BPRS of ≤54 at Screening. 
Key Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible to participate in the study: 
• Have one of the following psychiatric conditions: 
- 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 (C-SSRS-ideation) with the most recent episode 
occurring within the last 6 months. 
o Answer “Yes” to any of the 5 items (C-SSRS-behavior) with an episode occurring 
within the 6 months. 
• Have participated in another Corcept study with miricorilant. 
• Are currently taking more than one antipsychotic medication. 
• Have a history of a medical condition affecting body weight (e.g., poorly controlled 
hyper- or hypothyroidism; eating disorder such as anorexia, bulimia, or binge eating; or 
polycystic ovary syndrome). 


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• Are currently using or plan to use 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 (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. 
• 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 any elective surgery planned during the study. 
• Have had liposuction within 1 year of Screening or have planned liposuction during the study.  
• Have poorly controlled diabetes mellitus with 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 history of orthostatic hypotension with a systolic blood pressure decrease of ≥20 mm Hg 
or a diastolic blood pressure decrease of ≥10 mm Hg within the last year. 
• Have a history of a seizure disorder. 
• Are currently using any medications prohibited due to the potential for drug-drug interactions 
(DDI) with study treatments. Prohibited medications must be discontinued at least 5 half-lives 
prior to a patient receiving their first study treatment. Administration of concomitant 
medications are at the discretion of the Investigator and/or the Corcept Medical Monitor 
(see Section 5.5). 
• Have a clinically significant electrolyte abnormality at Screening.  
• Are currently using medication such as digoxin with an increased risk of toxicity in the event of 
electrolyte changes. 
• Are taking an unstable dosage (change in the dose within 4 weeks of 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.  
Study Drug, Dose, and Mode of Administration 
Study Drug: Miricorilant tablet, 150 mg or placebo for miricorilant tablet, 150 mg.  
Dose: 600 mg or 900 mg miricorilant, or placebo.  
Patients will be instructed to take a total of 6 tablets at approximately the same time each day. Patients 
who participate in the PK substudy must take the study drug in the mornings; these patients will be 
instructed to take their dose in the clinic during the Week 4 visit. 
• Those in the 600 miricorilant group will take 4 miricorilant tablets and 2 placebo tablets. 


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• Those in the 900 miricorilant group will take 6 miricorilant tablets. 
• Those in the placebo group will take 6 placebo tablets.  
Mode of Administration: oral administration with 8 oz (240 mL) of water, along with food.  
Criteria for Evaluation 
Study endpoints corresponding to study objectives are listed below. 
Primary Efficacy Endpoint 
Change from Baseline to Week 26 in body weight for both dose levels of miricorilant versus placebo. 
Secondary Efficacy Endpoints 
The following endpoints will be assessed: 
• Change from Baseline in body weight for both dose levels of miricorilant combined versus 
placebo.  
• Percentage of patients achieving a ≥5% weight loss for miricorilant versus placebo. 
• Change from Baseline in waist-to-hip ratio for miricorilant versus placebo. 
Exploratory Endpoints 
The following endpoints will be assessed relative to Baseline: 
• Change in body weight for miricorilant versus placebo in each subgroup of patients taking: 
- Olanzapine 
- Risperidone or paliperidone 
- Quetiapine 
• Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in patients who 
are not treated with insulin. 
In all patients: 
• Changes in ACTH, serum cortisol, and serum aldosterone (pharmacodynamic assessments). 
• Changes in BPRS, C-SSRS, CGI, OWLQOL, and WRSM. 
In patients with diabetes:  
• Change in HbA1c. 
• Change in fasting blood glucose. 
In patients with high blood pressure: 
• Change in blood pressure. 
Safety Endpoints 
The following endpoints will be assessed for miricorilant versus placebo: 
• Incidence of TEAEs, AEs, and SAEs.  
• Changes from Baseline in clinical laboratory tests (hematology and chemistry panels). 
• Changes from Baseline in physical examinations and vital sign. 
• Changes from Baseline in ECG parameters. 
Pharmacokinetic Endpoints 
• Key PK parameters estimated from steady-state plasma concentration. 


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Statistical Methods 
Statistical Analyses 
Analysis of the Primary Efficacy Endpoints 
The primary efficacy endpoint is based on the change in body weight from Baseline to Week 26. The 
primary analysis will use a mixed-effect model with repeated measures (MMRM) with change in body 
weight at each visit as the outcome variable; baseline body weight as a covariate; and antipsychotic 
medication (stratification factor), randomized treatment (600 mg or 900 mg miricorilant or placebo), 
visit, and treatment-by-visit interaction as fixed effects.  
The difference in body weight change at Week 26 between each miricorilant treatment group and 
placebo will be estimated from the model along with its associated 95% confidence interval (CI). 
The primary efficacy analysis will use the Efficacy Evaluable population. Neither CIs nor p-values will 
be adjusted for multiplicity.  
Analysis of the Secondary Efficacy Endpoints 
For the first secondary endpoint, the 2 miricorilant dose groups will be combined into a single 
treatment group and assessed using a similar model as the MMRM for the primary analysis. The other 
factors in the model will remain the same. The difference in body weight change at Week 26 between 
the combined miricorilant treatment groups and placebo will be estimated from the model along with 
its associated 95% CI. 
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 as a 
covariate, and antipsychotic medication and randomized treatment as fixed effects, will be used to 
compare each miricorilant dose group to placebo. 
Waist-to-hip ratio will be analyzed using similar models as the primary analysis of weight change. 
Differences between each miricorilant dose group and placebo will be estimated along with 
corresponding 95% CIs. Waist-to-hip ratio data may require a log-transformation prior to analysis. 
Analyses of Exploratory Endpoints 
The relationship between background antipsychotic medication and efficacy will be explored through 
subgroup analyses. Specifically, 3 MMRM analyses will be performed, one for each subgroup of 
patients taking olanzapine, risperidone or paliperidone, or quetiapine. Each MMRM will be similar to 
the primary analysis except all miricorilant dose groups will be combined into a single treatment group. 
Each model will use change in body weight at each visit as the outcome variable; baseline body weight 
as a covariate; and treatment (miricorilant or placebo), visit, and treatment-by-visit interaction as fixed 
effects. For each background medication, the difference in body weight change at Week 26 between the 
combined miricorilant dose groups and placebo will be estimated from the appropriate model along 
with its associated 95% CI and p-value.  
Analyses of continuous endpoints assessed at multiple post-treatment timepoints, such as the change in 
BPRS, CGI, OWLQOL, and WRSM from Baseline to Week 26 will be analyzed using models similar 
to the primary analysis of body weight change. C-SSRS results will be summarized descriptively. 
Endpoints like ACTH, serum cortisol, and serum aldosterone that are measured only at Baseline and 
Week 26 will be assessed using analysis of covariance (ANCOVA) models that include the change in 
the endpoint between Baseline and Week 26 as the outcome variable, baseline body weight as a 
covariate, and antipsychotic medication and randomized treatment as factors. 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. 


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HOMA-IR will be analyzed using similar models as the primary analysis of weight change. 
Differences between each miricorilant dose group and placebo will be estimated along with 
corresponding 95% CIs. HOMA-IR data may require a log-transformation prior to analysis. 
Dose response will be evaluated using an MMRM identical to that used for the primary analysis except 
that the placebo group will not be included. The difference between the miricorilant dose groups in the 
change in body weight at Week 26 will be estimated from the model using a linear contrast. The 
difference will be accompanied by an associated 95% CI and p-value.  
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 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. 
Pharmacokinetic Analysis 
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. 
Details of the PK analyses will be described in a PK analysis plan finalized before database lock. 
Sample Size 
The planned sample size is 150 subjects randomized 1:1:1 across 2 miricorilant treatment groups and 
1 placebo group. 
Fifty patients per group will ensure at least 90% power to detect a difference of 5 kg in mean change 
from Baseline in body weight between placebo and either miricorilant treatment group. These 
calculations assume a common standard deviation of 6 kg and a 0.05 two-sided significance level 
two-sample z-test. A drop-out rate of 40% from Baseline to Week 26 is assumed in this calculation. 
Randomization will be stratified by the type of antipsychotic medication used (one stratification factor 
with 3 levels). If ≥20 patients complete 26 weeks of treatment (10 patients treated with miricorilant and 
10 patients treated with placebo) in one of the allowed antipsychotic medication groups (olanzapine, 
risperidone or paliperidone, or quetiapine), this sample size provides 60% power to detect a difference 
in body weight change of 5 kg between the miricorilant and placebo groups, at alpha=0.1 level for that 
antipsychotic medication. The sample size estimates have not been adjusted for multiple comparisons. 
 


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CONTENTS 
CLINICAL STUDY PROTOCOL CORT118335-877 .................................................................. 1 
SPONSOR SIGNATURE PAGE ................................................................................................... 2 
PROTOCOL SYNOPSIS ............................................................................................................... 3 
CONTENTS .................................................................................................................................. 10 
List of Tables ................................................................................................................................ 17 
List of Figures ............................................................................................................................... 17 
List of Abbreviations and Definitions........................................................................................... 18 
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 ...................................... 23 
1.2.3 Safety Pharmacology and Toxicology .................................................................. 24 
1.3 
Clinical Summary ............................................................................................................. 25 
1.3.1 Phase 1 Study CORT118335-850 ......................................................................... 25 
1.3.2 Phase 1 Study CORT118335-851 ......................................................................... 27 
1.3.3 Phase 1 Study CORT118335-852 ......................................................................... 28 
1.3.4 Phase 1 Study CORT118335-853 ......................................................................... 29 
1.3.5 Phase 2 Study CORT118335-876 (GRATITUDE) .............................................. 30 
1.4 
Rationale for Study Design and Dosage Regimen ............................................................ 30 
1.4.1 Design Considerations .......................................................................................... 30 
1.4.2 Rationale for Dose Selection and Regimen .......................................................... 31 
1.5 
Benefits and Risks............................................................................................................. 31 
2 
STUDY OBJECTIVES ..................................................................................................... 33 
2.1 
Primary Efficacy Objective ............................................................................................... 33 


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2.2 
Secondary Efficacy Objectives ......................................................................................... 33 
2.3 
Exploratory Objectives ..................................................................................................... 33 
2.4 
Safety Objectives .............................................................................................................. 33 
2.5 
Pharmacokinetics Objective.............................................................................................. 33 
3 
STUDY DESIGN.............................................................................................................. 34 
3.1 
Overall Design .................................................................................................................. 34 
3.2 
Study Endpoints ................................................................................................................ 35 
3.2.1 Primary Efficacy Endpoint ................................................................................... 35 
3.2.2 Secondary Efficacy Endpoints .............................................................................. 35 
3.2.3 Exploratory Endpoints .......................................................................................... 35 
3.2.4 Safety Endpoints ................................................................................................... 35 
3.2.5 Pharmacokinetic Endpoints .................................................................................. 36 
3.3 
Number of Patients and Study Participation ..................................................................... 36 
3.3.1 Number of Patients ............................................................................................... 36 
3.3.2 Duration of Patient Participation .......................................................................... 36 
3.4 
Definitions: Enrollment, Study Completer, End of Treatment, and End of Study ........... 36 
3.4.1 Enrollment............................................................................................................. 36 
3.4.2 Study Completer ................................................................................................... 36 
3.4.3 End of Treatment .................................................................................................. 36 
3.4.4 End of Study ......................................................................................................... 36 
3.5 
Study Termination by Sponsor ......................................................................................... 36 
4 
STUDY POPULATION ................................................................................................... 38 
4.1 
Inclusion Criteria .............................................................................................................. 38 
4.2 
Exclusion Criteria ............................................................................................................. 39 
4.3 
Screen Failures .................................................................................................................. 40 
4.4 
Early Patient Discontinuation or Withdrawal ................................................................... 41 
4.4.1 Early Patient Discontinuation of Study Drug ....................................................... 41 
4.4.2 Early Patient Withdrawal from Study ................................................................... 42 
4.5 
Replacement of Patients .................................................................................................... 42 
4.6 
Restrictions/Requirements/Recommendations During Study ........................................... 42 


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4.6.1 Dietary Restrictions .............................................................................................. 42 
4.6.2 Alcohol .................................................................................................................. 42 
4.6.3 Activity ................................................................................................................. 42 
4.6.4 Childbearing Potential and Contraception ............................................................ 43 
4.6.5 Sperm Donation .................................................................................................... 44 
5 
STUDY TREATMENTS AND MANAGEMENT .......................................................... 45 
5.1 
Description of Study Drug, Dose, and Administration ..................................................... 45 
5.1.1 Description of Study Drug .................................................................................... 45 
5.1.2 Administration of Study Drug .............................................................................. 46 
5.2 
Non-Investigational Medicinal Agent............................................................................... 46 
5.3 
Safety Assessments ........................................................................................................... 46 
5.3.1 Monitoring of Liver Injury.................................................................................... 46 
5.3.2 Excessive GR/MR Antagonism ............................................................................ 46 
5.4 
Dose Modification ............................................................................................................ 47 
5.4.1 Dose Reduction ..................................................................................................... 47 
5.4.2 Dose Interruption and/or Discontinuation: General Criteria ................................ 47 
5.4.3 Dose Interruption and/or Discontinuation: Special Safety Events ....................... 47 
5.4.4 Pharmacokinetic Criteria for Dose Adjustment or Discontinuation ..................... 51 
5.5 
Concomitant Medications ................................................................................................. 51 
5.5.1 Permitted Concomitant Medications ..................................................................... 51 
5.5.2 Permitted Concomitant Therapy Requiring Caution ............................................ 51 
5.5.3 Prohibited Medications ......................................................................................... 52 
5.6 
Method of Study Drug Assignment and Randomization .................................................. 52 
5.7 
Blinding/Unblinding ......................................................................................................... 52 
5.8 
Dosing Diary ..................................................................................................................... 53 
5.9 
Study Drug Accountability and Treatment Adherence ..................................................... 53 
5.10 
Continued Access to Study Drug ...................................................................................... 53 
5.11 
External Data Review Committee(s) ................................................................................ 53 
5.11.1 Independent Data Monitoring Committee to Monitor Patient Safety ................... 53 
6 
DESCRIPTION OF STUDY ASSESSMENTS AND PROCEDURES AND 
APPROPRIATENESS OF MEASUREMENTS .............................................................. 54 


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6.1 
Informed Consent and Screening ...................................................................................... 54 
6.2 
Demographics and Baseline Disease Characteristics ....................................................... 54 
6.3 
Medical and Medication History ...................................................................................... 54 
6.4 
Safety Assessments ........................................................................................................... 55 
6.4.1 Physical Examination and Vital Signs .................................................................. 55 
6.4.2 Height .................................................................................................................... 55 
6.4.3 Electrocardiogram ................................................................................................. 55 
6.4.4 Adverse Events ..................................................................................................... 55 
6.4.5 Clinical Laboratory Assessments .......................................................................... 56 
6.4.5.1 Laboratory Parameters ........................................................................... 56 
6.4.5.2 Sample Collection, Preparation, and Shipping ...................................... 58 
6.4.5.3 Blood Volume Summary ....................................................................... 58 
6.5 
Efficacy Assessments........................................................................................................ 58 
6.6 
Pharmacokinetic Assessments .......................................................................................... 58 
6.7 
Pharmacodynamic/Biomarker Assessments ..................................................................... 59 
6.8 
Other Assessments ............................................................................................................ 59 
6.8.1 Clinician Assessed Outcomes ............................................................................... 59 
6.8.2 Patient Reported Outcomes................................................................................... 60 
6.9 
Appropriateness of the Measures ...................................................................................... 60 
7 
STUDY ASSESSMENTS AND PROCEDURES BY STUDY VISIT ............................ 61 
7.1 
Screening Period (Day -28 to Day -1) .............................................................................. 61 
7.2 
Baseline (Day 1) ............................................................................................................... 62 
7.3 
Treatment Period ............................................................................................................... 63 
7.3.1 Week 2: Study Day 15 (±2 days) .......................................................................... 63 
7.3.2 Week 4: Study Day 29 (±2 days) .......................................................................... 63 
7.3.3 Week 6: Study Day 43 (±2 days) .......................................................................... 64 
7.3.4 Week 8: Study Day 57 (±2 days) .......................................................................... 64 
7.3.5 Week 10: Study Day 71 (±5 days) ........................................................................ 64 
7.3.6 Week 12: Study Day 85 (±5 days) ........................................................................ 64 
7.3.7 Week 14: Study Day 99 (±5 days) ........................................................................ 64 
7.3.8 Week 16: Study Day 113 (±5 days) ...................................................................... 65 


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7.3.9 Week 18: Study Day 127 (±5 days) ...................................................................... 65 
7.3.10 Week 19: Study Day 134 (±5 days) ...................................................................... 65 
7.3.11 Week 20: Study Day 141 (±5 days) ...................................................................... 65 
7.3.12 Week 21: Study Day 148 (±5 days) ...................................................................... 66 
7.3.13 Week 22: Study Day 155 (±5 days) ...................................................................... 66 
7.3.14 Week 23: Study Day 162 (±5 days) ...................................................................... 66 
7.3.15 Week 24: Study Day 169 (±5 days) ...................................................................... 66 
7.3.16 Week 25: Study Day 176 (±5 days) ...................................................................... 66 
7.3.17 Week 26: Study Day 183 (±5 days) ...................................................................... 67 
7.4 
Early Termination Visit (In-Clinic Visit) ......................................................................... 67 
7.5 
Follow-Up Visit (In-Clinic Visit; 28±5 Days after Last Dose of Study Drug) ................ 68 
7.6 
Telephone Follow-Up Assessment of Survival ................................................................ 69 
7.7 
Unscheduled Visits ........................................................................................................... 69 
8 
SAFETY EVENT DOCUMENTATION AND REPORTING ........................................ 70 
8.1 
Investigator’s Responsibilities .......................................................................................... 70 
8.2 
Monitoring Safety Data During the Study ........................................................................ 70 
8.3 
Definition of an Adverse Event ........................................................................................ 70 
8.4 
Definition of a Serious Adverse Event ............................................................................. 71 
8.5 
Suspected Unexpected Serious Adverse Reaction (SUSAR) ........................................... 71 
8.6 
Expectedness ..................................................................................................................... 71 
8.7 
Clinical Significance ......................................................................................................... 72 
8.8 
Clinical Laboratory Adverse Events ................................................................................. 72 
8.9 
Documentation of Adverse Events ................................................................................... 72 
8.10 
Adverse Event Classification ............................................................................................ 73 
8.10.1 Intensity Grades of Adverse Events ...................................................................... 73 
8.10.2 Assessment of Causality: Relationship of Adverse Event to Study Drug or 
Study Procedure .................................................................................................... 73 
8.11 
Procedures for Reporting a Serious Adverse Event .......................................................... 74 
8.12 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as Adverse 
Events or Serious Adverse Events .................................................................................... 75 
8.13 
Recording Disease Progression......................................................................................... 75 


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8.14 
Recording Deaths .............................................................................................................. 75 
8.15 
Adverse Event Follow-up ................................................................................................. 75 
8.16 
Pregnancy .......................................................................................................................... 75 
8.16.1 Maternal Exposure ................................................................................................ 75 
8.16.2 Paternal Exposure ................................................................................................. 76 
8.17 
Treatment of Overdose ..................................................................................................... 76 
8.18 
Emergency Sponsor Contact ............................................................................................. 76 
9 
STATISTICAL METHODS ............................................................................................. 77 
9.1 
Analysis Populations ......................................................................................................... 77 
9.2 
Statistical Analyses ........................................................................................................... 77 
9.3 
Hypothesis Testing............................................................................................................ 78 
9.4 
Sample Size Calculation ................................................................................................... 78 
9.5 
Analysis Plan .................................................................................................................... 78 
9.5.1 Patient Disposition ................................................................................................ 78 
9.5.2 Demographic and Baseline Data ........................................................................... 78 
9.5.3 Prior and Concomitant Medications ..................................................................... 79 
9.5.4 Analysis of the Primary Efficacy Endpoints ......................................................... 79 
9.5.5 Approach to Missing Data Analysis ..................................................................... 79 
9.5.6 Analysis of the Secondary Efficacy Endpoints ..................................................... 79 
9.5.7 Analyses of Exploratory Efficacy Endpoints ........................................................ 79 
9.5.8 Safety Analyses ..................................................................................................... 80 
9.5.9 Pharmacokinetic Analysis ..................................................................................... 80 
9.5.10 Pharmacogenetic Analysis .................................................................................... 80 
9.5.11 Interim Analysis .................................................................................................... 81 
10 
ETHICAL AND LEGAL CONSIDERATIONS .............................................................. 82 
10.1 
Compliance with IRB Regulations ................................................................................... 82 
10.2 
Ethical Conduct of the Study ............................................................................................ 82 
10.3 
Protection of Human Patients ........................................................................................... 82 
10.3.1 Compliance with Informed-Consent Regulations ................................................. 82 
10.3.2 Patient Confidentiality .......................................................................................... 83 


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10.3.3 Patient Privacy ...................................................................................................... 83 
11 
ADMINISTRATIVE CONSIDERATIONS ..................................................................... 84 
11.1 
Quality Management ......................................................................................................... 84 
11.2 
Study Monitoring .............................................................................................................. 84 
11.3 
Documentation .................................................................................................................. 85 
11.3.1 Source Documentation .......................................................................................... 85 
11.3.2 Case Report Forms ................................................................................................ 85 
11.3.3 Retention of Study Essential Documents .............................................................. 85 
11.3.4 Sample Collection, Preparation, and Shipping ..................................................... 86 
11.4 
Long-Term Retention of Biological Samples ................................................................... 86 
11.5 
Clinical Supplies ............................................................................................................... 86 
11.5.1 Inventory, Reconciliation, Return, and Disposition of Clinical Supplies ............. 86 
11.5.2 Clinical-Supply Inventory ..................................................................................... 86 
11.5.3 Return or Destruction of Study Drug and/or Supplies .......................................... 87 
11.5.4 Study Drug Destroyed by the Site ........................................................................ 87 
11.5.5 Study Drug Returned to Sponsor for Destruction ................................................. 87 
11.5.6 Drug Accountability.............................................................................................. 87 
11.6 
Post-Trial Care .................................................................................................................. 87 
11.7 
Protocol Noncompliance ................................................................................................... 88 
11.8 
Financial Disclosure.......................................................................................................... 88 
11.9 
Publication and Disclosure Policy .................................................................................... 88 
11.10 Electronic Systems ............................................................................................................ 88 
12 
REFERENCES ................................................................................................................. 89 
13 
APPENDICES .................................................................................................................. 91 
Appendix A: Schedule(s) of Activities ......................................................................................... 92 
Appendix B: Summary of Changes .............................................................................................. 97 
 


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List of Tables 
Table 1  
Study Drug: Description, Packaging, and Storage .................................................45 
Table 2 
Criteria for Dose Interruption or Discontinuation Due to Special Safety Events ..48 
Table 3 
Permitted Concomitant Medications ......................................................................51 
Table 4 
Clinical Laboratory Variables Evaluated During the Study ..................................57 
Table 5 
Pharmacokinetic Parameters to be Evaluated* ......................................................59 
Table 6 
Adverse Event Grades Based on the Common Terminology Criteria for 
Adverse Events ......................................................................................................73 
Table 7 
Causal Attribution Guidance for Adverse Events ..................................................74 
Table 8 
Definitions of Analysis Populations ......................................................................77 
Table 9 
Schedule of Activities ............................................................................................92 
Table 10 
Summary of Changes in Protocol CORT118335-877 Amendment 5 ...................98 
 
List of Figures 
Figure 1  
Effect of Miricorilant on Body Weight in Female Rats Given Olanzapine ...........22 
Figure 2  
Reversal of Olanzapine-Induced Weight Gain in Female Rats .............................23 
Figure 3 
CORT118335-877 Study Design ...........................................................................34 
 


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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 
AR 
androgen receptor 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BMI 
body mass index 
BPRS 
Brief Psychiatric Rating Scale 
CDC 
Centers for Disease Control and Prevention 
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 
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 
HME 
hot melt extrudate 
HOMA-IR 
Homeostatic model assessment of insulin resistance 
IB 
Investigator’s Brochure 


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Abbreviation 
Definition 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IDMC 
Independent Data Monitoring Committee  
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IWRS 
interactive web response system 
Ki 
inhibition constant 
MINI 
Mini International Neuropsychiatric Interview 
MMRM 
mixed-effect model with repeated measures 
MR 
mineralocorticoid receptor 
NCI 
National Cancer Institute 
NOAEL 
no-observed-adverse-effect level 
OWLQOL 
Obesity Weight Loss Quality of Life 
PK 
pharmacokinetic(s) 
PR 
progesterone receptor 
QTc 
corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s equation: QTcF=QT/(RR⅓) 
RSI 
Reference Safety Information 
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 
WBC 
white blood cell  
WRSM 
Weight-Related Symptom Measure 


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1 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
1.1 
Therapeutic Area 
Antipsychotic-induced weight gain (AIWG) is a condition in which patients with schizophrenia 
and other disorders treated with antipsychotic medications gain weight, leading to increases in 
diabetes mellitus, dyslipidemia, cardiovascular disease, and mortality.  
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).  
1.1.1 Background 
Atypical antipsychotic medications were initially developed to overcome extrapyramidal effects 
(e.g., tardive dyskinesia) associated with first-generation antipsychotic medications. Atypical 
antipsychotic medications, although efficacious, tend to cause significantly more weight gain in 
patients than first-generation medications. Among the commonly used atypical antipsychotic 
medications, clozapine and olanzapine, followed by risperidone and quetiapine appear to cause 
the most weight gain (ADA/APA/AACE/NAASO 2004). In one study, olanzapine and clozapine 
caused between 4.0 to 4.5 kg of weight gain on a standard dose over the course of 10 weeks 
(Allison and Casey 2001). In addition to weight gain, patients on atypical antipsychotic 
medications develop drug-induced metabolic changes including increased insulin resistance and 
elevated levels of cholesterol and serum triglycerides that significantly increase their risk for 
cardiovascular disease (Dayabandara et al. 2017). Consequently, patients with schizophrenia 
have a 2–3 fold increased risk of mortality compared with the general population, corresponding 
to a 10–25 year reduction in life expectancy (Laursen et al. 2012). Furthermore, weight gain is 
also associated with discontinuation of antipsychotic medications, leading to a decrease in their 
effectiveness (Liebermann et al. 2005).  
1.1.2 Therapeutic Hypothesis 
The mechanism of AIWG remains poorly understood. Antipsychotic medications act on multiple 
neuroreceptors, and may increase appetite and decrease energy expenditure (Gothelf et al. 2002, 
Graham et al. 2005). Dysregulation of the hypothalamic-pituitary-adrenal axis has also been 
implicated with the use of atypical antipsychotics. For example, rats treated with clozapine 
showed an increase in corticosterone (Tulipano et al. 2007).  
In humans, there is evidence for a role for the glucocorticoid receptor (GR) in AIWG. 
In healthy volunteers treated with either olanzapine or risperidone, mifepristone, a GR 
antagonist, ameliorated the weight gain from the antipsychotic medication (Gross et al. 2009, 
Gross et al. 2010).  
More recently, miricorilant, which is a mixed agonist/antagonist of the GR and an antagonist of 
the mineralocorticoid receptor (MR), has been shown to mitigate weight gain in healthy 
volunteers taking olanzapine (Study CORT118335-852). 


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1.2 
Miricorilant: A Mixed Agonist/Antagonist of the Glucocorticoid-Receptor and 
Antagonist of the Mineralocorticoid-Receptor 
Miricorilant, a mixed agonist/antagonist of the GR and an antagonist of the MR, is currently 
being developed for the treatment of AIWG. The goals of this study (CORT118335-877) are to 
evaluate the safety, efficacy, and pharmacokinetics (PK) of miricorilant in reversing AIWG in 
obese patients (body mass index [BMI] ≥30 kg/m2) with schizophrenia currently taking 
olanzapine, risperidone, paliperidone (active metabolite of risperidone), or quetiapine. 
Further information about miricorilant is provided in the Investigator’s Brochure (IB).  
1.2.1 Nonclinical Summary 
1.2.1.1 
Pharmacology 
This section summarizes in vitro and in vivo data on the pharmacology of miricorilant as a 
high-affinity, mixed agonist/antagonist of the GR. In most models, mifepristone, which is an 
antagonist of the progesterone receptor (PR), androgen receptor (AR), and GR was used as an 
active comparator. Miricorilant has similar GR antagonism without effects on the PR or AR. 
1.2.1.1.1 In Vitro Pharmacology 
Miricorilant binds competitively and reversibly to the GR with high affinity (1.2 nM). Functional 
GR antagonism has been demonstrated in vitro by the ability of miricorilant to block the effects 
of dexamethasone (a potent and selective GR agonist) on tyrosine aminotransferase (TAT) 
activity in a human liver carcinoma cell line (inhibition constant [Ki], 100 nM) and a rat 
hepatoma cell line (Ki, 11 nM). Miricorilant prevented the dexamethasone-induced increase in 
TAT activity in primary hepatocytes from mice, monkeys, and humans. Miricorilant is also an 
antagonist of the MR, and has shown activity in both a reporter gene assay (Ki, 148 nM) and a 
protein:protein interaction assay (Ki, 140 nM). Both GR and MR antagonism are considered to 
contribute to the in vivo pharmacological activity of miricorilant. 
1.2.1.1.2 In Vivo Pharmacology 
The most commonly used animal model of AIWG 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 et al. 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. 
Three studies (MPI 950-033, MPI 950-034, and MPI 950-035) evaluated the ability of 
miricorilant, at various doses, to prevent weight gain in female rats (10 per group) that were 
administered the antipsychotic medication olanzapine and fed a normal diet. 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).  


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In Study MPI 950-035, miricorilant doses ≥0.6 mg/kg/day demonstrated a dose-dependent 
inhibition of olanzapine-induced weight gain (Figure 1; Hunt et al. 2012).  
Figure 1  
Effect of Miricorilant on Body Weight in Female Rats Given Olanzapine 
  
Source: Hunt et al. 2012, MPI 950-035. 
CORT118335=miricorilant. 
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 (MPI 950-144, RenaSci RS1738, and 
RenaSci RS1854).  
In the first study (MPI 950-144), rats were fed a normal diet, and were either administered 
olanzapine at a dose of 1.2 mg/kg twice a day, (i.e., 2.4 mg/kg/day, for 56 consecutive days) or 
received only vehicle throughout the duration of the study.  
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 olanzapine-induced increase in body weight 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 or a split dose of 1 mg/kg twice a day, were similar. Effects were observed from the 
first week of dosing and persisted through the remainder of the study.  


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Figure 2  
Reversal of Olanzapine-Induced Weight Gain in Female Rats 
 
Source: MPI 950-144. 
CORT118335=miricorilant. 
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 resulted 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 was investigated in two studies (RenaSci RS1738 
and RS1854), and doses as low as 0.5 mg/kg/day fully reversed the effects of olanzapine.  
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). Additionally, 
in vitro data showed the potential for modest inhibition of CYP3A4, CYP2C8, and CYP2C9 by 
miricorilant (Corcept PK-118335-004 and Corcept PK-118335-009). 
Fecal elimination represented the principal route of elimination with 98.7% ± 2.48% recovered. 


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1.2.3 Safety Pharmacology and Toxicology 
The nonclinical safety of miricorilant was evaluated in preliminary ascending single- and 
repeat-dose studies followed by Good Laboratory Practice (GLP) 28-day, 91-day repeat-dose 
and chronic toxicology studies in mice and monkeys. Definitive GLP reproductive toxicology 
studies were conducted in mice and rabbits, and 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), were performed. 
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 a maximum inhibition of hERG-mediated potassium currents of 23.8%. 
Mouse and monkey GLP 28 day (1 month), 91 day (3-month), 179 day (6-month; mice) and 
270 day (9-month; monkey) general toxicology studies were conducted with miricorilant, which 
was dosed daily by oral gavage: 
• Mice were administered doses of 30, 100, 300, or 500 mg/kg for 28 days (MPI 950-126) 
and 30, 100, or 500 mg/kg for 91 days (MPI 950-140). No adverse effects were observed 
at any dose in either of these two studies. Therefore, the no-observed-adverse-effect-level 
(NOAEL) was 500 mg/kg.  
• Monkeys administered doses of 20, 100, or 400 mg/kg for 28 days showed no adverse 
effects at any dose in this study. Therefore, the NOAEL was 400 mg/kg (MPI 950-127). 
Monkeys were administered doses of 20, 50, or 200 mg/kg for 91 days. Although no 
adverse effects were noted in female monkeys (for a NOAEL of 200 mg/kg), the NOAEL 
was 50 mg/kg for male monkeys, because adverse clinical effects, specifically abnormal 
feces, decreased activity, lack of appetite, hunched posture, dehydration and ataxia, were 
noted at the highest dose (MPI 950-139). 
• 
Mice were administered doses of 30, 100 and 300 mg/kg for 6 months. No adverse 
effects were observed, and the NOAEL was 300 mg/kg in both sexes (MPI 950-155). 
• Monkeys were administered doses of 15, 50 and 150 mg/kg for 9 months. No adverse 
effects were observed, and the NOAEL was 150 mg/kg in both sexes (MPI 950-156). 
Other treatment-related findings in the nonclinical studies are considered related to the mode of 
action of miricorilant as a GR mixed agonist/antagonist 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 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).  


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Reproductive toxicity studies have been completed in mice and rabbits as follows: 
• In the definitive GLP reproductive toxicology study conducted in pregnant mice, 
miricorilant was administered daily by oral gavage at doses of 1, 10 and 100 mg/kg/day 
(MPI 950-177) from gestation day (GD) 6 through 15. The NOAEL for maternal toxicity 
was 10 mg/kg/day due to reduced body weight gain at the 100 mg/kg/day dose. The 
NOAEL for developmental toxicity was 1 mg/kg/day. At higher doses skeletal 
malformations were observed, including cleft palate.  
• In the definitive GLP reproductive toxicology study conducted in female rabbits 
(MPI 950-178), miricorilant was administered daily by oral gavage at doses of 1, 3, 
and 10 mg/kg/day from GD 7 through 19. The NOAEL for maternal toxicity was 
10 mg/kg/day and the NOAEL for developmental toxicity was 1 mg/kg/day. A dose 
of 10 mg/kg/day resulted in adverse pregnancy outcomes (abortions, resorbed fetuses, 
postimplantation loss), decreased gravid uterine weights and decreased fetal body weight. 
Skeletal abnormalities were also observed at this dose, although these were considered 
non-adverse. A dose of 3 mg/kg/day resulted in decreased uterine weights and decreased 
fetal weights. 
These data indicate that 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 and men with partners of childbearing potential in clinical 
studies must use highly efficacious forms of birth control as outlined in Section 4.6.4. 
Additional 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 
ongoing Study CORT118335-853) and one Phase 2 study (Study CORT118335-876; 
GRATITUDE). Study CORT118335-876 is an ongoing Phase 2, double-blind study conducted 
in obese patients with schizophrenia to assess the ability of miricorilant in reversing recent 
AIWG. Available safety and PK data from these five 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 
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 in suspension. The SAD/suspension portion of the study also evaluated 


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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 
as single doses under both 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 subject experienced a serious adverse event (SAE) of 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 
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. 


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Holter Electrocardiogram: Exposure-Response Analysis 
Holter monitoring was conducted in the MAD/suspension parts of the study. No subject had an 
increase in QTcF >30 ms based on Holter readings.  
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 21‒23 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 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 tablets) 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 exposure 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 miricorilant tablets) is 
approximately 25% lower than the predicted Cmax of 140 ng/mL based on dose-proportionality.  
Following administration of 200 mg miricorilant (2 × 100 mg tablets) under fed conditions 
(a high-fat breakfast), miricorilant Cmax, AUClast and AUCinf increased by 1.8-, 2.2- and 2.1-fold, 
respectively, compared with 200 mg miricorilant administered under fasting conditions.  
1.3.2 Phase 1 Study CORT118335-851 
CORT118335-851 was an open-label study conducted with [14C]-miricorilant to assess the 
absolute oral 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 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. 


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Safety Results 
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. No SAEs or AEs leading to discontinuation were reported. 
No clinically significant findings in any of the vital signs or laboratory evaluations were 
reported. Single ECGs were obtained unless abnormalities were detected. No subject recorded 
QTcF intervals that were >450 msec at any time point and no subject had increases in QTcF 
interval from baseline that were >30 msec. 
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. 
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.  


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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. 
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 
this Phase 2 study (CORT118335-877). 
Safety Results 
As of June 25, 2020, no deaths or SAEs have been reported in this ongoing study. 


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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. 
1.3.5 Phase 2 Study CORT118335-876 (GRATITUDE)  
This is a Phase 2, randomized, double-blind, placebo-controlled study to investigate the ability of 
miricorilant to treat recent AIWG caused by any oral or injectable atypical antipsychotic 
medication (except clozapine) in obese patients (BMI ≥30 kg/m2) with schizophrenia or bipolar 
disorder; patients who have been on antipsychotic medication for 18 months or less and have 
demonstrated weight gain of ≥5% within 6 months of starting the medication are eligible. In this 
multi-center study, approximately 70 patients with schizophrenia or bipolar disorder, and 
AIWG will be randomized in a 1:1 ratio to 600-mg miricorilant (6 × 100 mg tablets) or placebo 
for 12 weeks, and the safety, efficacy, and PK of miricorilant will be evaluated.  
This study is currently ongoing. 
Safety Results 
As of June 25, 2020, no deaths have been reported in this ongoing double-blinded study. 
One patient presented with SAEs of malignant hyperthermia and sympathomimetic drug 
intoxication following worsening schizophrenia after self-discontinuation of his antipsychotic 
medication. This event was considered not related to study drug (miricorilant or placebo).  
1.4 
Rationale for Study Design and Dosage Regimen  
1.4.1 Design Considerations 
This is a study of miricorilant, a mixed agonist/antagonist of the GR and an antagonist of the 
MR, in obese patients with schizophrenia taking antipsychotic medications. There is evidence 
that GR antagonism may alleviate AIWG. In healthy volunteers treated with olanzapine or 
risperidone, mifepristone (a GR antagonist) ameliorated weight gain associated with these 
medications (Gross et al. 2009, Gross et al. 2010). Additionally, results from the Phase 1 
Study CORT118335-852 show that miricorilant has been shown to mitigate weight gain in 
healthy volunteers taking olanzapine.  
The ongoing Phase 2 Study CORT118335-876 (GRATITUDE) is designed to investigate 
the ability of miricorilant to treat recent AIWG in patients with schizophrenia or bipolar disorder 
on antipsychotic medication when treated for 12 weeks. In this study, patients with schizophrenia 
with long-standing weight gain due to antipsychotic medication will be treated for a longer 
duration (26-week regimen) with miricorilant to evaluate its ability to reverse AIWG. 
Specifically, this study will compare 2 doses of miricorilant (600 mg and 900 mg) to placebo, 
and determine whether once daily dosing of miricorilant for 26 weeks results in reversal of 
AIWG in obese patients (BMI ≥30 kg/m2) with schizophrenia who have been taking olanzapine, 


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risperidone, paliperidone, or quetiapine. This study will be conducted in the US at approximately 
35 sites and will randomize approximately 150 obese patients to a 1:1:1 ratio of 600 mg 
miricorilant, 900 mg miricorilant, or placebo in a double-blind manner to reduce bias.  
The study will consist of 4 weeks of Screening, 26 weeks of Treatment, and 4 weeks of 
Follow-up. The efficacy of miricorilant versus placebo in reversing AIWG will be assessed. 
Clinical benefit will also be assessed through patient-reported outcomes such as the Obesity 
Weight Loss Quality of Life scale (OWLQOL) and Weight-Related Symptom Measure (WRSM) 
questionnaires. Routine assessments of safety will consist of AE monitoring, measurement of 
vital signs, 12-lead ECG recordings, physical examination, and clinical laboratory safety tests. 
In the PK substudy, to be conducted in a subgroup of approximately 45 patients, samples will be 
collected to determine standard PK parameters for miricorilant. 
1.4.2 Rationale for Dose Selection and Regimen 
Miricorilant is effective at mitigating and reversing weight gain in rat studies described in 
Section 1.2.1. 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; likewise miricorilant at 900 mg as a divided dose for 14 days confirmed 
these weight mitigation results (CORT118335-852, summarized in Section 1.3.3). Study 
CORT118335-877 is designed to evaluate the safety and tolerability of miricorilant in reversing 
long-standing AIWG with the same total doses used in Study CORT118335-852. The 600 mg 
dose is predicted to be a minimally effective dose. The 900 mg dose given once daily is included 
as a second dose in this study to evaluate the efficacy and the dose/exposure relationship. The 
safety of 900 mg has been previously established in Phase 1 Studies CORT118335-850 and 
CORT118335-852. 
1.5 
Benefits and Risks 
Miricorilant has shown efficacy in rat models of AIWG and has also been shown to mitigate 
weight gain in healthy volunteers taking olanzapine. 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 on atypical 
antipsychotic medications develop drug-induced metabolic changes that significantly increase 
their risk for cardiovascular disease (Dayabandara et al. 2017). Consequently, patients with 
schizophrenia have a 2–3 fold increased risk of mortality compared with the general population, 
corresponding to a 10–25 year reduction in life expectancy (Laursen et al. 2012). Reversal or 
possibly prevention of AIWG is expected to provide a clinically meaningful improvement in 
general health outcomes and life expectancy in patients taking antipsychotic medications. 
Based on the totality of data for miricorilant, the potential for clinically relevant drug-drug 
interactions in this study is low. The elimination of olanzapine, risperidone, paliperidone, and 
quetiapine is primarily through hepatic metabolism with contribution by CYP1A2, CYP2D6, 
and/or CYP3A4. Although miricorilant has shown modest inhibitory potential of CYP3A4 
in vitro (Corcept PK-118335-004), miricorilant can be used in combination with these 
antipsychotic medications. Additionally, there is no evidence that GR antagonism interferes 
with the efficacy of these antipsychotic medications. 


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The risk of clinically significant safety concerns is considered low. However potential adverse 
effects of miricorilant may include a combination of 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 
MR antagonism (e.g., hyperkalemia and hypotension).  
Olanzapine, risperidone, paliperidone, and quetiapine additionally have both orthostatic 
hypotension and drug induced leukopenia/neutropenia as reported adverse reactions. Patients 
who are at risk for clinically significant leukopenia/neutropenia or clinically significant 
orthostatic hypotension will be excluded from the study. Orthostatic vital signs will be measured 
at each study visit, including follow-up. 
Patients will be closely monitored during the study. Standard safety tests such as chemistry 
panels (refer to Table 4) will be performed at scheduled visits 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 or oral hydrocortisone and intravenous fluids. Further information for monitoring 
and treating excessive GR or MR antagonism is provided in Section 5.3.2 and 5.4.3. 


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2 
STUDY OBJECTIVES 
2.1 
Primary Efficacy Objective 
• To assess the efficacy of both dose levels of miricorilant versus placebo in 
reversing AIWG. 
2.2 
Secondary Efficacy Objectives 
• To assess the efficacy of both dose levels of miricorilant combined versus placebo 
in reversing AIWG.  
• To assess the efficacy of miricorilant versus placebo in improving markers of 
cardiovascular risk such as waist-to-hip ratio.  
2.3 
Exploratory Objectives 
• To assess the efficacy of miricorilant versus placebo in reversing AIWG for each 
subgroup of patients taking: 
– Olanzapine 
– Risperidone or paliperidone (active risperidone metabolite) 
– Quetiapine 
• To assess the efficacy of miricorilant versus placebo in reducing insulin resistance in 
patients not treated with insulin. 
• To be assessed by patient group: 
– In all patients, change in adrenocorticotropic hormone (ACTH), serum cortisol, 
serum aldosterone, Brief Psychiatric Rating Scale (BPRS), Columbia Suicide 
Severity Rating Scale (C-SSRS), Clinical Global Impression (CGI) Scale, Obesity 
Weight Loss Quality of Life scale (OWLQOL) and Weight-Related Symptom 
Measure (WRSM). 
– In patients with diabetes, change in glycated hemoglobin (HbA1c) and fasting 
blood glucose. 
– In patients with high blood pressure, change in blood pressure. 
• To evaluate the dose-response relationship between miricorilant and change in 
body weight. 
• To evaluate the exposure-response relationship between miricorilant and change 
in body weight. 
2.4 
Safety Objectives 
• To assess the safety of miricorilant versus placebo. 
2.5 
Pharmacokinetics Objective 
• To assess the PK of both dose levels of miricorilant. 


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3 
STUDY DESIGN 
3.1 
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 currently taking olanzapine, risperidone, paliperidone, or quetiapine. 
The study consists of the following study periods: 
• Screening Period: Up to 28 days 
• Treatment Period: Day 1 (Baseline) to Week 26 
• Follow-up Period: 4 weeks after last dose of study drug  
 
The study design is illustrated in Figure 3. 
Figure 3 
CORT118335-877 Study Design 
 
Abbreviations: PK, pharmacokinetics; W, week. 
 
Approximately 150 patients who are eligible for participation in the study will be randomized on 
Day 1 in a 1:1:1 ratio to 600 mg miricorilant, 900 mg miricorilant, or placebo, for 26 weeks of 
treatment. Randomization will be stratified by background antipsychotic medication (3 strata: 
olanzapine, risperidone or paliperidone, or quetiapine) to ensure approximately equal numbers of 
patients within each stratum are assigned to the 600 mg miricorilant, 900 mg miricorilant, and 
placebo groups. See Section 9.4 for details regarding sample size calculation.  
Patients will be encouraged to volunteer for the PK substudy, which will be conducted at the 
Week 4 visit. Approximately 45 patients are expected to participate. In patients who consent to 
participate, blood samples for the measurement of miricorilant plasma concentrations will be 
collected according to the PK plan. 


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3.2 
Study Endpoints 
3.2.1 Primary Efficacy Endpoint 
Change from Baseline to Week 26 in body weight for both dose levels of miricorilant versus 
placebo. 
3.2.2 Secondary Efficacy Endpoints 
The following endpoints will be assessed: 
• Change from Baseline in body weight for both dose levels of miricorilant combined 
versus placebo.  
• Percentage of patients achieving a ≥5% weight loss for miricorilant versus placebo. 
• Change from Baseline in waist-to-hip ratio for miricorilant versus placebo. 
3.2.3 Exploratory Endpoints 
The following endpoints will be assessed relative to Baseline: 
• Change in body weight for miricorilant versus placebo in each subgroup of patients 
taking: 
– Olanzapine 
– Risperidone or paliperidone 
– Quetiapine 
• Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in patients 
who are not treated with insulin. 
In all patients: 
• Changes in ACTH, serum cortisol, and serum aldosterone (pharmacodynamic 
assessments). 
• Changes in BPRS, C-SSRS, CGI, OWLQOL, and WRSM. 
In patients with diabetes:  
• Change in HbA1c. 
• Change in fasting blood glucose. 
In patients with high blood pressure: 
• Change in blood pressure. 
3.2.4 Safety Endpoints 
The following endpoints will be assessed for miricorilant versus placebo: 
• Incidence of TEAEs, AEs, and SAEs.  
• Changes from Baseline in clinical laboratory tests (hematology and chemistry panels). 
• Changes from Baseline in physical examinations and vital sign measurements. 
• Changes from Baseline in ECG parameters. 


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3.2.5 Pharmacokinetic Endpoints 
Key PK parameters will be estimated from steady state plasma concentrations of miricorilant 
(see Section 6.6, Table 5 for PK variables to be analyzed). 
3.3 
Number of Patients and Study Participation 
3.3.1 Number of Patients 
Approximately 150 patients will be randomized on Day 1 in a 1:1:1 ratio to 600 mg miricorilant, 
900 mg miricorilant, or placebo, for 26 weeks of treatment. The PK substudy will be conducted 
at the Week 4 visit; approximately 45 patients are expected to participate.  
3.3.2 Duration of Patient Participation 
The maximum expected duration of a patient’s participation is 34 weeks (4 weeks of Screening, 
26 weeks of Treatment, and 4 weeks of Follow-up). 
3.4 
Definitions: Enrollment, Study Completer, End of Treatment, and End of Study 
3.4.1 Enrollment 
Patients are considered enrolled in the study when they meet the study enrollment criteria.  
3.4.2 Study Completer 
Patients are considered to have completed the study if they complete all 26 weeks of Treatment. 
3.4.3 End of Treatment 
The end of treatment is defined as the date on which the patient received his or her last dose of 
the study drug, which may be the end of the Treatment Period if the patient received all doses of 
the study drug or may be earlier, if the patient discontinued the study drug before the designated 
stopping point at Week 26. 
3.4.4 End of Study 
The end of study is defined as the date of last contact (i.e., visit, telephone, e-mail) with the last 
patient in the study.  
3.5 
Study Termination by Sponsor 
If Corcept (the Sponsor), the 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 the Sponsor 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 the patients enrolled in 
the study. 


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• Decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product. 
Study termination (if required) and follow-up will be performed in compliance with applicable 
regulations and guidelines. 


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4 
STUDY POPULATION 
The following eligibility criteria are designed to select obese patients (BMI ≥30 kg/m2) with 
schizophrenia currently taking olanzapine, risperidone, paliperidone, or quetiapine, 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. Meet the criteria for schizophrenia based on medical history and the Mini International 
Neuropsychiatric Interview (MINI).  
4. Are currently taking olanzapine, risperidone, paliperidone, or quetiapine; long-acting, 
injectable formulations of olanzapine, risperidone, paliperidone are acceptable.  
5. Have gained weight from treatment with olanzapine, risperidone, paliperidone, or 
quetiapine (patient must meet at least one criterion from each column):  
Self-Assessment: 
 Corroborated Reports: 
• Noticeable weight gain 
(~10 pounds or more) after 
initiation of antipsychotic 
medication  
 
 
• 
Clinician or other health professional 
verifies that patient has gained weight 
(~10 pounds or more) since initiation 
of antipsychotic medication 
• Increase in clothing size by two 
size units (e.g., size 10 to 14) after 
initiation of antipsychotic 
medication 
 
 
 
• 
Caretaker or close friend/family 
member verifies that patient has 
gained weight (~10 pounds or more) 
since initiation of antipsychotic 
medication 
• Increase in pant waist size by 
4 inches (e.g., size 32 to 36) after 
initiation of antipsychotic 
medication 
 
 
 
• 
Hospital or medical records indicate 
that patient has gained ≥5% of 
baseline weight since initiation of 
antipsychotic medication 
6. Have a BMI ≥30 kg/m2.  
7. Have been on the same dose of antipsychotic medication for the last month prior 
to Screening. 
8. Are clinically stable and unlikely to require change to their antipsychotic medication 
(i.e., switch medication or change dose) through the duration of the study (34 weeks). 
9. Have a BPRS of ≤54 at Screening. 
10. Agree to use highly effective methods of contraception throughout the study and for at 
least 28 days after the last dose of assigned treatment (for women of childbearing 
potential or men with a sexual partner of childbearing potential); see Section 4.6.4 and 
4.6.5. 


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4.2 
Exclusion Criteria 
Patients who meet any of the following exclusion criteria will not be eligible to participate in the 
study: 
1. Have one of the following psychiatric conditions: 
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. 
ii. Answer “Yes” to any of the 5 items (C-SSRS-behavior) with an episode occurring 
within the 6 months. 
2. Have participated in another Corcept study with miricorilant. 
3. Are currently taking more than one antipsychotic medication. 
4. Have a history of a medical condition affecting body weight (e.g., poorly controlled hyper- 
or hypothyroidism; eating disorder such as anorexia, bulimia, or binge eating; or polycystic 
ovary syndrome). 
5. 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. 
6. 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. 
7. Have any elective surgery planned during the study. 
8. Have had liposuction within 1 year of Screening or have planned liposuction during 
the study.  
9. Have poorly controlled diabetes mellitus with HbA1c >10% or a fasting blood 
glucose >200 mg/dL. 
10. 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. 


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11. Have a history of symptomatic hypotension with a systolic blood pressure <100 mm Hg or 
a diastolic blood pressure <60 mm Hg. 
12. Have a history of orthostatic hypotension with a systolic blood pressure decrease of 
≥20 mm Hg or a diastolic blood pressure decrease of ≥10 mm Hg within the last year. 
13. Have a history of a seizure disorder. 
14. Are currently using any medications prohibited due to the potential for drug-drug 
interactions (DDI) with the study drug. Prohibited medications must be discontinued at 
least 5 half-lives prior to a patient receiving their first dose of the study drug. 
Administration of concomitant medications are at the discretion of the Investigator and/or 
the Corcept Medical Monitor (see Section 5.5). 
15. Have a clinically significant electrolyte abnormality at Screening. 
16. Are currently using medication such as digoxin with an increased risk of toxicity in the 
event of electrolyte changes. 
17. Are taking an unstable dosage (change in the dose within 4 weeks of Screening) of a 
medication that may change the fluid or electrolyte status such as a diuretic 
18. 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/1.73 m2. 
d. AST or ALT >3 × the upper limit of normal. 
e. White blood cell (WBC) count below the limit of normal.  
f. Absolute neutrophil count <1,500 neutrophils/µL. 
19. Have a clinically significant ECG abnormality as judged by the Investigator. 
20. Have a QTcF >450 ms for men or QTcF >470 ms for women. 
21. Are breast feeding, pregnant, or planning a pregnancy. 
22. Have any clinical condition or significant concurrent disease judged by the Investigator to 
complicate the evaluation of the study drug. 
23. Previous exposure to investigational drugs taken within 3 months or 5 half-lives of the 
investigational drug prior to Screening, whichever is longer. 
24. Are employees or immediate family members of the clinical site staff or Corcept 
employees. 
25. 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).  
26. Have a history of illicit drug use within the last 12 months including, but not limited to, 
cocaine, heroin, ecstasy, lysergic acid diethylamide (LSD) or other hallucinogens, and 
ketamine. 
27. Are seropositive for hepatitis B or hepatitis C. 
28. Patients with a known HIV infection. 
29. 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 did not 
meet eligibility criteria for the study and were not randomized to the study drug.  


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Patients who have an exclusionary laboratory, ECG, or vital sign result on initial screening tests 
may have that assessment repeated in consultation with the Corcept Medical Monitor 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 with the 
approval of the Corcept 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 the study drug 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 administration of the study drug, 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]). 
4.4.1 Early Patient Discontinuation of Study Drug  
Study drug 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 but are not limited to 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 26 (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 26 visit at the very least in addition to the ET and Follow-Up visits. The 
date when the patient discontinues the study drug and the reason for discontinuation must be 
recorded on the eCRF. 
For guidelines about temporary interruption of study drug, see Section 5.4. 


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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 drug and/or failure to adhere to the study 
requirements, as specified in protocol. 
• Lost to follow-up (before a patient is determined to be lost to follow-up, reasonable 
efforts will be made to contact the patient and complete study termination procedures).  
• 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. As noted above, if 
a patient wishes to withdraw consent to further participation in the study entirely, including 
follow-up, this should be clearly documented (1) in the patient’s medical record and signed by 
the Investigator and (2) in the clinical study database (eCRF). 
4.5 
Replacement of Patients 
Not applicable.  
4.6 
Restrictions/Requirements/Recommendations During Study 
The following apply to patients in this study (prohibited or limited-use medications are described 
in Section 5.5).  
4.6.1 Dietary Restrictions  
Patients will be asked to follow a healthy diet according to the American Heart Association 
guidelines (AHA 2020).  
4.6.2 Alcohol  
Patients will be advised to limit alcohol use (also see Section 4.2 regarding alcohol abuse).  
4.6.3 Activity  
Patients should engage in physical activity as possible and are recommended to follow the 
Centers for Disease Control and Prevention (CDC) guidelines of 150 minutes per week of 
moderate-intensity aerobic activity (CDC 2020). Patients are advised to gradually increase their 
activity level to meet this guideline. 


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4.6.4 Childbearing Potential and Contraception  
Miricorilant should not be administered to pregnant women due to adverse effects on fetal 
development (mice) or adverse pregnancy outcomes (rabbits). Men and women of childbearing 
potential who participate in this study must agree to use effective contraception.  
All female patients of childbearing potential (including all women <50 years old, women whose 
surgical sterilization was performed <6 months prior to Screening, and women who have had a 
menstrual period in the last 12 months) will take pregnancy tests at scheduled visits 
(Appendix A). The Screening pregnancy test will be a blood test. All subsequent pregnancy tests 
will be urine tests. 
• A female patient is of childbearing potential if, in the opinion of the Investigator, she is 
biologically capable of having children. 
• Female patients who are considered not of childbearing potential must meet at least 1 of 
the two following criteria: 
a. Have undergone a documented hysterectomy and/or bilateral oophorectomy. 
b. 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. 
Female patients of childbearing potential are required and must agree to use a highly effective 
method of contraception throughout the study and for at least 28 days following the last dose of 
study drug administration.  
Male patients with female partners are required and must agree to use 2 forms of contraception, 
one of which is a barrier method, throughout the study and for at least 28 days following the last 
dose of study drug administration.  
Highly effective forms of contraception include: 
a. Abstinence 
Abstinence is only acceptable as true abstinence (i.e., when this is in line with the 
preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods), declaration of abstinence for the duration of a 
study, and withdrawal do not constitute abstinence. 
b. Intrauterine device or intrauterine system 
c. Oral contraceptive plus a barrier method 
d. Diaphragm with vaginal spermicidal cream 
e. Vaginal spermicide with a condom  
f. Surgical sterilization (≥6 months postsurgery)  
If a patient is usually not sexually active but becomes active, they, with their partner, must 
comply with the contraceptive requirements detailed above.  


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4.6.5 Sperm Donation 
Male patients must agree not to donate sperm during the study and for at least 28 days after the 
last dose of study drug administration. 


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5 
STUDY TREATMENTS AND MANAGEMENT 
5.1 
Description of Study Drug, Dose, and Administration  
5.1.1 Description of Study Drug  
Study drug is defined as miricorilant tablet, 150 mg or placebo for miricorilant tablet, 150 mg. 
Description of the study drug, including packaging and storage, is described in Table 1. 
Table 1  
Study Drug: Description, Packaging, and Storage 
Specifications 
Miricorilant 
Placebo 
Description 
Miricorilant tablet, 150 mg is oval shaped 
and white to off-white in color. 
Each tablet contains 150 mg of miricorilant 
and the following inactive ingredients: 
methacrylic acid-methyl methacrylate 
copolymer, sodium lauryl sulfate, 
hypromellose acetate succinate, 
microcrystalline cellulose, croscarmellose 
sodium, silicon dioxide, and magnesium 
stearate.  
Placebo for miricorilant tablet, 150 mg is 
designed to match the study drug in 
appearance. It is oval shaped and is white to 
off-white in color. 
Each tablet contains microcrystalline 
cellulose. 
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. 
Unit Dose 
Strength 
Miricorilant tablet, 150 mg  
Placebo for miricorilant tablet, 150 mg 
Dose levels 
600 mg and 900 mg 
N/A 
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 
Dispensing study 
drug 
Dispense to patients at the visits specified in 
Appendix A 
Dispense to patients at the visits specified in 
Appendix A  
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. 


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5.1.2 Administration of Study Drug 
Patients will be randomized in a 1:1:1 ratio to 600 mg miricorilant, 900 mg miricorilant or 
placebo. Study drug will be administered once daily, orally with 8 oz (240 mL) of water, along 
with food. 
Patients will be instructed to take a total of 6 tablets at approximately the same time each day.  
• Those in the 600 miricorilant group will take 4 miricorilant tablets and 2 placebo tablets. 
• Those in the 900 miricorilant group will take 6 miricorilant tablets. 
• Those in the placebo group will take 6 placebo tablets.  
Patients who participate in the PK substudy must take the study drug in the mornings; these 
patients will be instructed to take their dose in the clinic during the Week 4 visit. 
5.2 
Non-Investigational Medicinal Agent  
Not applicable.  
5.3 
Safety Assessments 
5.3.1 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.  
5.3.2 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 as a 
combination of 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 (including 
Baseline) and in the follow-up period. If excessive GR and/or MR antagonism is suspected, 
patients should discontinue the study medication, and administration of intravenous fluids, 
and intravenous or oral hydrocortisone should begin without delay and the actions outlined in 
Table 2 should be taken. The half-life of miricorilant is approximately 21 to 23 hours 
(Study CORT118335-850). Symptoms should continue to be monitored even after the last dose 
of study medication in the follow-up period. 


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5.4 
Dose Modification 
5.4.1 Dose Reduction 
No dose reduction will be allowed. 
5.4.2 Dose Interruption and/or Discontinuation: General Criteria 
Treatment with study drug should be temporarily interrupted if deemed medically necessary by 
the Investigator. On interrupting treatment, the Investigator should notify the Corcept Medical 
Monitor.  
Before restarting treatment with study drug, the Investigator must obtain approval from the 
Corcept Medical Monitor. If the event that necessitated treatment interruption recurs after study 
drug is restarted, the patient should be permanently discontinued from treatment. 
In addition, patients will be permanently discontinued from treatment if they experience any of 
the criteria listed for stopping treatment with the study drug in Table 2. 
5.4.3 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 Interruption or Discontinuation Due to Special Safety Events 
Safety Event 
Criteria for Interrupting and Restarting Study Drug and Patient 
Management 
Criteria for Stopping Study Drug 
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 intravenous fluids, as indicated. 
• If appropriate, administer supplemental glucocorticoids given in high doses to 
overcome the GR antagonism produced by miricorilant. Initially, consider 
intravenous hydrocortisone, followed by additional intravenous 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 drug. 
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 
intravenous 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 
intravenous 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 
intravenous and oral hydration. 


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Safety Event 
Criteria for Interrupting and Restarting Study Drug and Patient 
Management 
Criteria for Stopping Study Drug 
• 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 Drug and Patient 
Management 
Criteria for Stopping Study Drug 
• 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; MR, mineralocorticoid receptor; SBP, systolic blood pressure; TBL, total bilirubin level; 
ULN, upper limit of normal. 


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5.4.4 Pharmacokinetic Criteria for Dose Adjustment or Discontinuation 
Not applicable.  
5.5 
Concomitant Medications 
Administration of concomitant medications are at the discretion of the Investigator and/or the 
Corcept Medical Monitor.  
5.5.1 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 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 drug. 
All medications (other than the study drug) administered 28 days of 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 treatment with study drug 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 treatment with study drug 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 for DDI. 
Anxiolytic medication such as 
benzodiazepines 
No restrictions unless there is a potential for DDI. 
5.5.2 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 
• Substrates metabolized predominantly by CYP3A4, CYP2C8, and/or CYP2C9 with a 
narrow therapeutic index 
• Strong inhibitors of CYP3A4, CYP2C8, and/or CYP2C9 


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• Medications that carry a possible risk for QT prolongation  
The Corcept Medical Monitor should be contacted in the case of any clarifications regarding 
concomitant therapy.  
5.5.3 Prohibited Medications 
The following medications are prohibited during treatment with miricorilant in this study: 
• 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 
5.6 
Method of Study Drug Assignment and Randomization 
All patients will be randomly assigned to the study drug (one of the 3 treatment groups) using a 
centralized interactive web response system (IWRS). Subject unique identifier creation and 
treatment allocation will be performed using the system. Randomization will be stratified by 
background antipsychotic medication (3 strata: olanzapine, risperidone or paliperidone, or 
quetiapine). 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 SoA (Appendix A).  
Returned study drug should not be re-dispensed to patients. However, study drug brought back 
by the patient for accounting reasons can be returned to the patient. 
5.7 
Blinding/Unblinding 
This is a double-blind, placebo-controlled study. Tablets (miricorilant,150 mg or placebo for 
miricorilant tablet, 150 mg) are 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 
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 drug assignment. To maintain the overall quality and legitimacy of the clinical trial, 
unblinding should only occur in exceptional circumstances. These circumstances could include 
but are not limited to pregnancy of the patient or pregnancy of the patient’s partner. The Corcept 
Medical Monitor must be notified before the blind is broken unless identification of the study 
drug is required for a medical emergency in which the knowledge of the specific blinded study 


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drug will affect the immediate management of the patient’s condition (e.g., antidote available). 
In this case, the Sponsor 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. 
Investigators wishing to discuss potential unblinding occurrences may contact the Corcept 
Medical Monitor for further discussion.  
5.8 
Dosing Diary 
A dosing diary will be provided, and patients will be instructed to return all unused study 
tablets and the dosing diary at their visits. Patients should complete an entry in the diary for 
each self-administered dose of the study drug and note the names and doses of any concomitant 
medications taken. Entries will include the number of tablets and the date and time of the study 
drug administration. Time and dose administered should be documented in the clinic charts. 
5.9 
Study Drug Accountability and Treatment Adherence  
Study drug adherence will be determined by review of the dose diary (Section 5.8) and counting 
returned tablets. 
A patient who is assigned a study drug (i.e., to 600 mg miricorilant, 900 mg miricorilant or 
placebo, for 26 weeks of treatment) will be considered nonadherent if he or she misses >30% of 
the prescribed doses during the study, unless the patient’s study drug 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 drug. 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. 
5.10 
Continued Access to Study Drug 
There is no provision for continued access to study drug. 
5.11 
External Data Review Committee(s) 
5.11.1 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 and in the 
conduct and monitoring of randomized clinical trials. The IDMC will meet at least quarterly. 
Further details describing the IDMC meeting frequency, 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 for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines 
for 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 (Appendix A). 
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 (see 
Section 4.3), 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 
Demographics and Baseline Disease Characteristics 
Patient demographic data, including age, sex, and race, and baseline disease characteristics will 
be documented at Screening.  
6.3 
Medical and Medication 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. 


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6.4 
Safety Assessments 
Safety will be determined from evaluation of AEs, physical examinations, clinical laboratory 
tests, vital signs, and ECGs. 
6.4.1 Physical Examination and Vital Signs  
Physical examinations including a basic neurologic examination will be performed as indicated 
in the SoA (Appendix A). 
If clinically significant abnormalities are observed during Screening, they should be reported in 
the patient’s medical history; if observed any time after the first dose of study drug (Day 1), they 
will be considered TEAEs. 
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 within 1–3 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 as 
indicated in the SoA (Appendix A). At Baseline, the 12-lead resting ECG (in triplicate) will be 
performed both before and after dosing. 
Patients should be lying down resting for approximately 15 minutes before each ECG evaluation. 
A central reviewer will be used; instructions will be provided in the imaging manual.  
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 the 
study drug. 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, cortisol, and aldosterone levels 
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. 


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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. 
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 (see Section 8.8). The Common Terminology Criteria for Adverse 
Events (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). 


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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  
Blood urea nitrogen 
Uric acid  
Bicarbonate  
Total protein  
Gamma-glutamyl transferase (GGT) 
Drug screen 
Pharmacodynamic Biomarkers 
Adrenocorticotropic hormone 
(ACTH) (morning) 
Serum cortisol (morning) 
Serum aldosterone 
Pharmacokinetics 
Miricorilant  
Other Biomarkers  
Glucocorticoid-receptor activity 
Pregnancy 
Serum/urine pregnancy test (for 
women of childbearing potential) 
Lipid Panel 
Hormones 
Total cholesterol 
Direct low-density lipoprotein-
cholesterol 
High-density lipoprotein-cholesterol 
Very-low-density lipoprotein 
cholesterol 
Triglycerides (fasting only) 
Follicle-stimulating hormone 
(FSH) 
Ad Hoc Testing 
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) 
Thyroid Function 
Thyroid-stimulating hormone (TSH) 
Free thyroxine (T4) 
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 as indicated in the SoA (Appendix A). Body weight will be 
measured without overcoat and shoes, and with only light clothing.  
Waist circumference will be measured for all patients as indicated in the SoA (Appendix A). 
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 autocalculated in electronic data capture (EDC) 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 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. 
Miricorilant plasma concentration will be used to estimate relevant PK parameters, which will be 
reported as applicable (Table 5). PK data may also be used in safety and/or efficacy evaluations 
related to concerns arising during or after the study. Drug concentration information that would 
unblind the study will not be reported to investigative sites or blinded personnel until the study 
has been unblinded. 


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Table 5 
Pharmacokinetic Parameters to be Evaluated* 
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 
CL/F 
apparent oral clearance  
Cmax 
maximum concentration over the dosing interval 
Ctau 
concentration at the end of the dosing interval 
t1/2 
apparent terminal elimination half-life 
tlag 
latest time after dosing before the first quantifiable concentration 
tlast  
time of the last quantifiable concentration 
Tmax 
time to maximum concentration 
Vss/F 
apparent oral volume of distribution at steady state 
*This table does not contain a comprehensive list of PK parameters. The final list of PK parameters reported may 
exclude some of these parameters and/or include additional parameters. 
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 the SoA (Appendix A). These samples will be used to develop a better understanding 
of the mechanisms of both treatment response (predictive biomarkers) and disease processes 
(prognostic biomarkers) and ultimately to identify patients who do or do not have a high 
probability to benefit from treatment with miricorilant. 
6.8 
Other Assessments 
6.8.1 Clinician Assessed Outcomes 
The clinician assessed outcome assessments in the study include the BPRS, C-SSRS, CGI, and 
MINI. 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. 


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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 MINI International Neuropsychiatric Interview for Psychotic Disorders is a brief structured 
interview for the major psychiatric disorders in DSM-5 and ICD-10. 
6.8.2 Patient Reported Outcomes  
Health-related quality of life scores will be measured using self-reported OWLQOL 
questionnaire and WRSM. Both the OWLQOL and the WRSM are intended to be administered 
together. The 17-item OWLQOL measures behavior and feelings that are associated with obesity 
and weight loss using a 7-point response scale that ranges from 0 “not at all” to 6 “a very great 
deal”. The WRSM is a 20-item measure of the symptoms associated with obesity and obesity 
treatment, along with the degree to which each symptom “bothers the individual”.  
The questionnaires will be completed from Baseline until Follow-up and should always be 
conducted prior to dosing when conducted on study drug administration days. 
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 
An SoA is provided in Appendix A. 
Corcept will be promptly notified of any protocol deviations.  
The acceptable visit window during the Treatment Period for Day 1 through Week 8 
visits is ±2 days and for Week 10 to Week 26 is ±5 days. 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 provide 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 is 
randomized to receive the study drug is 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 the Screening 
clinic visit (at least 8 hours). 
The following Screening procedures will be performed: 
• Obtain informed consent 
• Record medical history 
• Conduct MINI  
• Record prior and concomitant medications 
• Record AEs 
• Record demographic information 
• Perform urine drug test 
• Measure height and body weight 
• Perform physical examination 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Conduct psychological assessments (BPRS, C-SSRS, and CGI) 
• Perform laboratory tests: 
– Hematology with platelet and WBC count differential 
– Chemistry panel (fasting) 
– Lipid panel (fasting) 
– HbA1c 
– Serum pregnancy test (women of child-bearing potential) 
– FSH test (only for women who have medically confirmed ovarian failure or are 
postmenopausal) 
– Hepatitis B (HBV) screening  


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– Hepatitis C (HCV) 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 
• Measure body weight 
• Measure waist circumference 
• Measure hip circumference 
• 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 ±1 hour) 
– Serum insulin (fasting) 
– Plasma glucose (fasting) 
– Serum cortisol (morning–8 AM ±1 hour) 
– Serum aldosterone 
– TSH 
– Free 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 
• Other Biomarker Assessment: 
– Glucocorticoid-receptor activity marker 
• Conduct psychological assessments (BPRS, C-SSRS, and CGI) 
• Perform health related OWLQOL and WRSM questionnaires  
• Provide dietary and exercise counseling 
• Record any AEs 
• Perform study randomization 
• Dispense study drug; patient will take their first dose of the study drug in the clinic at this 
visit after clinic assessments 


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• Provide the patient with dose diary 
7.3 
Treatment Period 
The following will be performed as indicated in the SoA, (Appendix A): 
• Record any AEs 
• Record concomitant medications 
• Perform physical examination 
• Measure body weight 
• Measure waist circumference 
• Measure hip circumference 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Conduct psychological assessments (BPRS, C-SSRS, and CGI) 
• Perform health related OWLQOL and WRSM questionnaires  
• Record unused study drug brought back by the patient 
• Evaluate adherence to treatment based on returned dose diary and counting unused 
study drug 
In addition, assessments will be performed at specific visits of the Treatment Period as indicated 
in the following sections. 
7.3.1 Week 2: Study Day 15 (±2 days) 
• Perform assessments listed in Section 7.3 
• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel 
– Hematology with platelet and WBC differential 
7.3.2 Week 4: Study Day 29 (±2 days) 
• Perform assessments listed in Section 7.3 
• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
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 drug on 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. 


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7.3.3 Week 6: Study Day 43 (±2 days) 
• Perform assessments listed in Section 7.3 
• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
7.3.4 Week 8: Study Day 57 (±2 days) 
• Record any AEs 
• Record concomitant medications 
• Measure body weight 
• Record unused study drug brought back by the patient 
• Evaluate adherence to treatment based on returned dose diary and counting unused 
study drug 
• Perform laboratory tests: 
– Chemistry panel  
7.3.5 Week 10: Study Day 71 (±5 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 
• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel (fasting) 
– Hematology with platelet and WBC differential  
– Lipid panel (fasting) 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
7.3.6 Week 12: Study Day 85 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Measure body weight 
• Record unused study drug brought back by the patient 
• Evaluate adherence to treatment based on returned dose diary and counting unused 
study drug 
• Perform laboratory tests: 
– Chemistry panel 
7.3.7 Week 14: Study Day 99 (±5 days) 
• Perform assessments listed in Section 7.3 


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• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
– HbA1c  
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
• Provide a refresher on dietary and exercise counseling on weight loss 
7.3.8 Week 16: Study Day 113 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Measure body weight 
• Record unused study drug brought back by the patient 
• Evaluate adherence to treatment based on returned dose diary and counting unused 
study drug 
• Perform laboratory tests: 
– Chemistry panel 
7.3.9 Week 18: Study Day 127 (±5 days) 
• Perform assessments listed in Section 7.3 
• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
7.3.10 Week 19: Study Day 134 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
7.3.11 Week 20: Study Day 141 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Measure body weight 
• Record unused study drug brought back by the patient 
• Evaluate adherence to treatment based on returned dose diary and counting unused 
study drug 


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• Perform laboratory tests: 
– Chemistry panel 
– Hematology with platelet and WBC differential 
7.3.12 Week 21: Study Day 148 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
7.3.13 Week 22: Study Day 155 (±5 days) 
• Perform assessments listed in Section 7.3 
• Dispense study drug 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
7.3.14 Week 23: Study Day 162 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
7.3.15 Week 24: Study Day 169 (±5 days) 
• Record any AEs 
• Record concomitant medications 
• Measure body weight 
• Record unused study drug brought back by the patient 
• Evaluate adherence to treatment based on returned dose diary and counting unused 
study drug 
• Perform laboratory tests: 
– Chemistry panel 
– Hematology with platelet and WBC differential 
7.3.16 Week 25: Study Day 176 (±5 days) 
• Record any AEs 
• Record concomitant medications 


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• Perform laboratory tests: 
– Chemistry panel  
– Hematology with platelet and WBC differential 
7.3.17 Week 26: Study Day 183 (±5 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 ±1 hour) 
– Serum cortisol (morning–8 AM ±1 hour) 
– Serum aldosterone 
– TSH 
– Free T4 
– HbA1c 
– Urine pregnancy test (women of child-bearing potential); if urine pregnancy test is 
positive, the result should be confirmed with a serum pregnancy test 
• Other Biomarker Assessment: 
– 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 (26 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 returned dose diary and counting unused 
study drug 
• Perform physical examination 
• Measure body weight 
• Measure waist circumference 
• Measure hip circumference 


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• 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 (fasting) 
– Lipid panel (fasting) 
– HbA1c 
– Serum insulin (fasting) 
– Plasma glucose (fasting) 
– TSH 
– Free T4 
– ACTH (morning–8 AM ±1 hour) 
– Serum cortisol (morning–8 AM ±1 hour) 
– Serum aldosterone 
• Other Biomarker Assessment: 
– Glucocorticoid-receptor activity marker 
• Conduct psychological assessments (BPRS, C-SSRS, and CGI) 
• Perform health related OWLQOL and WRSM questionnaires  
7.5 
Follow-Up Visit (In-Clinic Visit; 28±5 Days after Last Dose of Study Drug) 
For patients who complete 26 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 
• Measure waist circumference 
• Measure hip circumference 
• 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 (BPRS, C-SSRS, and CGI) 
• Perform health related OWLQOL and WRSM questionnaires  


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7.6 
Telephone Follow-Up Assessment of Survival 
Not applicable.  
7.7 
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. All SAEs must be reported to the Sponsor 
within 24 hours from awareness of the event.  
The Investigator (or medically qualified designee) is responsible for determining whether 
an AE is clinically/medically significant. All available information regarding the AE must be 
documented on the eCRF (or in the patient’s medical record). 
8.2 
Monitoring Safety Data During the Study 
Safety results collected during the study (e.g., AEs, laboratory results, physical findings) will 
be monitored on an ongoing basis by the Corcept Medical Monitor and the Investigator. All 
abnormal laboratory results, and 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 laboratory results, and ECG and vital-signs findings. All 
Grade 3 and above findings will immediately be reported to the Corcept Medical Monitor 
within 24 hours.  
The Sponsor or its designee will promptly evaluate all reported safety information against 
cumulative product experience to identify and expeditiously communicate possible new safety 
findings to Investigators and applicable regulatory authorities. Investigators, in turn, are 
responsible for notifying their IRB of new safety findings according to their local requirements.  
In addition, an IDMC will be established to conduct periodic reviews of data to ensure the safety 
of patients (see Section 5.11). 
8.3 
Definition of an Adverse Event 
An AE is defined as any unfavorable or unintended sign (including an abnormal laboratory 
finding that is inconsistent with the patient’s baseline findings), symptom, or disease (new or 
exacerbated) temporally associated with the use of a study drug, whether considered related to 
the study drug or not. 
Examples of AEs include: 
• New conditions recorded after signing the ICF. 
• Worsening of a chronic or intermittent pre-existing condition, including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome. 
• Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either the study drug 
or a concurrent medication. 


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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 defined as any untoward medical occurrence that, at any dose: 
• Results in death. 
• Is in the opinion of the Investigator immediately life threatening (i.e., the patient is at 
immediate risk of death; it does not include a reaction that, had it occurred in a more 
severe form, might have caused death). 
• Requires inpatient hospitalization or results in prolongation of an existing 
hospitalization. a 
• Results in persistent or significant disability or incapacity. b 
• Is a congenital anomaly or birth defect. 
• Is an important medical event that may not be immediately life-threatening, result in 
death, or require hospitalization, but based on appropriate medical judgment, it 
jeopardizes the patient, or may require medical or surgical intervention to prevent one of 
the outcomes listed. 
a  In general, hospitalization signifies that the patient was admitted to the hospital for observation and/or 
treatment (usually involving at least an overnight stay) that would not have been appropriate in the 
physician’s office or in an outpatient setting. 
b  The term disability means a substantial disruption of a person’s ability to conduct normal life functions (or 
substantially different from their pre-treatment, baseline functional abilities). This definition is not intended to 
include experiences of relatively uncomplicated influenza and accidental trauma (e.g., a sprained ankle) that 
may interfere or prevent everyday life functions, but do not constitute substantial disruption. 
The following are NOT considered SAEs: 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
the patient’s baseline. 
• Hospitalization for social/convenience considerations. 
• Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience. 
The Investigator should institute any clinically necessary supplementary investigation of SAE 
information. In the case of patient death, any post-mortem findings/reports will be requested. 
8.5 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
A suspected unexpected adverse reaction is a serious adverse reaction that is both unexpected, 
i.e., not present in the product’s Reference Safety Information (RSI) and meets the definition 
of an SAE, the specificity or severity of which is not consistent with those specifically noted 
in the RSI. 
8.6 
Expectedness 
An SAE is considered unexpected if not reported in the RSI section of the IB or if the event is of 
greater severity or frequency than described in the IB. 


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8.7 
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. 
8.8 
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 modification 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. All Grade 3 and above findings will immediately be reported to the Corcept Medical 
Monitor within 24 hours. 
8.9 
Documentation of Adverse Events 
Patients will be evaluated and questioned to identify AEs during the study. Grade 3 and above 
AEs are to be reported to the Sponsor as soon as the Investigator becomes aware. 
Collection of AEs will start immediately following signing of the ICF and will continue 
throughout the study (including the 28 day Follow-up period) as noted in the SoA (Appendix A). 
AEs that occur after start of study treatment following randomization to the study drug and up to 
and including 28 days after administration of the last dose of the study drug will be considered 
TEAEs. Any AEs reported more than 28 days after the last dose of study drug will be considered 
posttreatment AEs. 
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). 
If 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 that are drug-related and unexpected (not specified in the RSI section of the 
Investigator’s Brochure) or if the event is of greater severity or frequency than that described in 
the Investigator’s Brochure) must be reported to the governing IRB and governing health 
authorities as required.  


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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 Section 8.10.1), (4) relationship to the study drug (see Section 8.10.2), (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 the study drug. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
unifying diagnosis whenever possible, rather than individual underlying signs and symptoms.  
8.10 
Adverse Event Classification 
8.10.1 Intensity Grades of Adverse Events 
The seriousness and severity of an AE are different assessments. 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 6 
should be used to evaluate the grade of severity for the AE. 
Table 6 
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). 
8.10.2 Assessment of Causality: Relationship of Adverse Event to Study Drug or 
Study 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 7. The Investigator’s 
assessment of causality must be provided for all AEs (serious and nonserious) as required for 
safety reporting to health authorities. 
Alternative causes, such as the natural history of the underlying disease(s), concomitant therapy, 
other risk factors, and the temporal relationship of the AE or SAE to the study drug should be 
considered and investigated. 


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There may be situations when an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to the Sponsor. However, it is critical that the 
Investigator assesses causality for every SAE prior to the transmission of the SAE report to the 
Sponsor, since the causality assessment is one of the criteria used when determining regulatory 
reporting requirements. The Investigator may change his/her opinion of causality in light of 
follow-up information received, amending the SAE report accordingly. 
Several factors should be considered in making this assessment, including: 
• Temporal relationship of the AE to the administration of the study treatment/study 
procedure. 
• Whether an alternative etiology has been identified. 
• Mechanism of action of the study drug. 
• Biological plausibility. 
Table 7 
Causal Attribution Guidance for Adverse Events 
Not related to study drug  
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 drug. The cause must be noted 
on the AE eCRF. 
Possibly related to study drug 
An AE that might be due to the use of the drug. 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 drug 
An AE that might be due to the use of the drug. The relationship in time is 
suggestive. An alternative explanation is less likely, e.g., concomitant 
drug(s) or concurrent disease(s). 
Related to study drug 
An AE that is due to the use of the drug. 
8.11 
Procedures for Reporting a Serious Adverse Event 
Any SAE occurring from the time of informed consent and for up to 28 days after the last dose 
of the study drug must be reported within 24 hours to the Corcept Medical Monitor and to the 
designated safety contact, and recorded on the SAE Form. All patients with an SAE must be 
followed and the outcomes reported. The Investigator must supply the Sponsor and the IRB with 
any additional requested information (e.g., autopsy reports and terminal medical reports). 
SAE reporting details are provided below: 
 
 
 
 


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8.12 
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 8.9 and 8.11, 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. 
8.13 
Recording Disease Progression 
Not applicable. 
8.14 
Recording Deaths 
When recording a death as an SAE, the AE that caused or contributed to the fatal outcome 
should be recorded as a single medical concept. If the cause of death is unknown and cannot be 
ascertained at the time of the reporting, record as “unexplained death”.  
8.15 
Adverse Event Follow-up 
All AEs considered to be related to the study drug (see Section 8.10.2 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. Responses to follow-up queries about the reported 
event(s) should be recorded and reported to the Sponsor as soon as possible. 
8.16 
Pregnancy 
All pregnancies and outcomes of pregnancy should be reported to the Sponsor during the study 
and within 28 days of the last dose of the study drug(s). 
8.16.1 Maternal Exposure 
If a patient becomes pregnant during the study, study drug should be discontinued immediately. 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the study drug 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 study drug, 
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 
managed as SAEs. Elective abortions without complications should not be considered 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 the pregnancy, even if the patient discontinued the study. 
The Investigator or designee should ensure that all relevant information is provided to the 
responsible Clinical Safety Group All pregnancy outcomes must be reported by the Investigator 
within 24 hours after he or she becomes aware of it. 


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8.16.2 Paternal Exposure 
Pregnancy of the patient’s partner is not considered 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 of study drug should be followed and documented; live births resulting from these 
pregnancies may be followed for up to two months after delivery.  
8.17 
Treatment of Overdose 
There is currently no experience with overdose of miricorilant. For monitoring symptoms of 
excessive GR and MR antagonism, refer to Section 5.4.3. 
8.18 
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 the study drug), 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 
9.1 
Analysis Populations 
The analysis populations are defined in Table 8.  
Table 8 
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 drug. 
Modified Intent-to-Treat 
(mITT) Population a 
All patients who receive at least 1 dose of study drug. 
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. 
PK Population 
All patients who have evaluable PK data. 
Abbreviations: PK, pharmacokinetics. 
a. An Intent-to-Treat (ITT) Population is defined as all patients who are randomized into the study even if they do 
not receive any study drug. The mITT Population includes all randomized patients who start study drug. 
 
Summaries of demographics and baseline conditions will be done for the 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 may also be performed on the Modified Intent-to-Treat (mITT) 
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 
Statistical Analyses 
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. 


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9.3 
Hypothesis Testing 
Evaluating the primary objective entails comparing each of the 2 miricorilant treatment groups 
independently to placebo on the primary endpoint, the change in body weight from Baseline to 
Week 26. For each test, the null hypothesis is that there is no difference between miricorilant and 
placebo in change in body weight. The alternative hypothesis is that there is a difference between 
groups. Each of the 2 hypotheses will be assessed at a 2-sided α=0.05 significance level with no 
adjustment to α for multiplicity. 
9.4 
Sample Size Calculation 
The planned sample size is 150 subjects randomized 1:1:1 across 2 miricorilant treatment groups 
and 1 placebo group. 
Fifty patients per group will ensure at least 90% power to detect a difference of 5 kg in mean 
change from Baseline in body weight between placebo and either miricorilant treatment group. 
These calculations assume a common standard deviation of 6 kg and a 0.05 two-sided 
significance level two-sample z-test. A drop-out rate of 40% from Baseline to Week 26 is 
assumed in this calculation. 
Power is greater if the difference in change from Baseline in body weight between treatment and 
placebo is greater than 5 kg. For example, assuming there is a dose-response relationship where 
the difference between treatment and placebo is 6 and 7 kg in the 600 and 900 mg miricorilant 
groups, respectively, power would be 97% and 99% for detecting a difference between each 
miricorilant group and placebo. 
Randomization will be stratified by the type of antipsychotic medication used (one stratification 
factor with 3 levels). If ≥20 patients complete 26 weeks of treatment (10 patients treated with 
miricorilant and 10 patients treated with placebo) in one of the allowed antipsychotic medication 
groups (olanzapine, risperidone or paliperidone, or quetiapine), this sample size provides 
60% power to detect a difference in body weight change of 5 kg between the miricorilant and 
placebo groups, at alpha=0.1 level for that antipsychotic medication. The sample size estimates 
have not been adjusted for multiple comparisons. 
9.5 
Analysis Plan 
9.5.1 Patient Disposition 
Patient disposition summaries will include the number of enrolled patients, the number of 
patients in each analysis population, the number of patients who complete the study, and the 
number of patients who terminate the study early broken out by the primary reason for 
discontinuation. 
9.5.2 Demographic and Baseline Data 
Categorical demographic and baseline data will be summarized by frequency while continuous 
variables will be summarized by mean, standard deviation, median, minimum, and maximum. 
Summarizes will be presented by treatment group and for all patients combined. 


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9.5.3 Prior and Concomitant Medications 
Verbatim terms will be mapped to Anatomical Therapeutic Chemical class and Generic Drug 
Names using the most current version of the World Health Organization Drug Dictionary. The 
number and percentage of patients will be presented for each medication by treatment group and 
for all patients combined. 
9.5.4 Analysis of the Primary Efficacy Endpoints 
The primary efficacy endpoint is based on the change in body weight from Baseline to Week 26. 
The primary analysis will use a mixed-effect model with repeated measures (MMRM) with 
change in body weight at each visit as the outcome variable; baseline body weight as a covariate; 
and antipsychotic medication (stratification factor), randomized treatment (600 mg or 900 mg 
miricorilant or placebo), visit, and treatment-by-visit interaction as fixed effects. The difference 
in body weight change at Week 26 between each miricorilant treatment group and placebo will 
be estimated from the model along with its associated 95% confidence interval (CI). 
The primary efficacy analysis will use the Efficacy Evaluable population. Neither CIs nor 
p-values will be adjusted for multiplicity.  
9.5.5 Approach to Missing Data Analysis 
Sensitivity analyses will be specified in the SAP.  
9.5.6 Analysis of the Secondary Efficacy Endpoints 
For the first secondary endpoint, the 2 miricorilant dose groups will be combined into a single 
treatment group and assessed using a similar model as the MMRM for the primary analysis. The 
other factors in the model will remain the same. The difference in body weight change at 
Week 26 between the combined miricorilant treatment groups and placebo will be estimated 
from the model along with its associated 95% CI. 
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 as a covariate, and antipsychotic medication (stratification factor) and randomized 
treatment as fixed effects, will be used to compare each miricorilant dose group to placebo. 
Waist-to-hip ratio will be analyzed using similar models as the primary analysis of weight 
change. Differences between each miricorilant dose group and placebo will be estimated along 
with corresponding 95% CIs. Waist-to-hip ratio data may require a log-transformation prior 
to analysis. 
9.5.7 Analyses of Exploratory Efficacy Endpoints 
The relationship between background antipsychotic medication and efficacy will be explored 
through subgroup analyses. Specifically, 3 MMRM analyses will be performed, one for each 
subgroup of patients taking olanzapine, risperidone or paliperidone, or quetiapine. Each MMRM 
will be similar to the primary analysis except all miricorilant dose groups will be combined into a 
single treatment group. Each model will use change in body weight at each visit as the outcome 
variable; Baseline body weight as a covariate; and treatment (miricorilant or placebo), visit, and 


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treatment-by-visit interaction as fixed effects. For each background medication, the difference in 
body weight change at Week 26 between the combined miricorilant dose groups and placebo will 
be estimated from the appropriate model along with its associated 95% CI and p-value.  
Analyses of continuous endpoints assessed at multiple post-treatment timepoints, such as the 
change in BPRS, CGI, OWLQOL, and WRSM from Baseline to Week 26 will be analyzed using 
models similar to the primary analysis of body weight change. C-SSRS results will be 
summarized descriptively. Endpoints like ACTH, serum cortisol, and serum aldosterone that are 
measured only at Baseline and Week 26 will be assessed using analysis of covariance 
(ANCOVA) models that include the change in the endpoint between Baseline and Week 26 as 
the outcome variable, baseline body weight as a covariate, and antipsychotic medication and 
randomized treatment as factors. 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. 
HOMA-IR will be analyzed using similar models as the primary analysis of weight change. 
Differences between each miricorilant dose group and placebo will be estimated along with 
corresponding 95% CIs. HOMA-IR data may require a log-transformation prior to analysis 
Dose response will be evaluated using an MMRM identical to that used for the primary analysis 
except that the placebo group will not be included. The difference between the miricorilant dose 
groups in the change in body weight at Week 26 will be estimated from the model using a linear 
contrast. The difference will be accompanied by an associated 95% CI and p-value.  
9.5.8 Safety Analyses 
Adverse events will be mapped to system organ classes and preferred terms using the Medical 
Dictionary for Regulatory Activities (MedDRA). TEAEs will be summarized overall and 
displayed by system organ class and preferred term, as well as by severity, seriousness, and 
relationship to the study drug. Serious AEs and AEs that lead to study drug 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. 
9.5.9 Pharmacokinetic Analysis 
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. 
Details of the PK analyses will be described in a PK analysis plan finalized before database lock. 
9.5.10 Pharmacogenetic Analysis 
Not applicable. 


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9.5.11 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 or local regulations. The protocol, IB, 
ICFs, recruitment materials, and all patient materials will be submitted to the IRB for review and 
approval. Approval of the clinical trial must be obtained before any patient is enrolled, and the 
Investigator must submit written approval to the Sponsor before enrolling any patient. 
The Investigator is responsible for ensuring annual reviews by the IRB occur, and that they 
receive approval. The Investigator is also responsible for informing the IRB of any amendment 
to the protocol in accordance with local requirements before implementing any changes.  
Any changes to the ICF must be approved by the IRB. A determination will be made as to 
whether previously consented patients need to be re-consented. Other documents related to the 
clinical trial may also need IRB approvals prior to implementing.  
The Sponsor or their designee 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 retained and provided to the 
Sponsor or their designee. 
Progress reports and notifications, including required safety information, 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 must be obtained from each patient before initiating any study-
mandated screening procedures, or enrollment into the study. The ICF will contain all of the 
elements required by ICH guidelines for GCP and any additional elements required by local 
regulations. 
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 informed consent process discussion should be documented in patient’s record. 
Investigator(s) must maintain the original, signed ICF. A copy of the signed ICF must be given 
to the patient. 


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The ICF should include information about possible retention of biological samples at the 
conclusion of this study, the purpose of retaining the samples and the time period for which they 
will be retained. With the patient’s permission, samples, including blood, plasma, serum, and 
tissue, may be retained for  
• Future identification of biomarkers of disease or miricorilant treatment.  
• Future analysis of active metabolite concentrations and possible biomarkers related to 
drug response. 
10.3.2 Patient Confidentiality 
To maintain patient confidentiality, all source documents, study reports, and communications 
will identify the patient by the assigned patient number.  
The Investigator will grant monitor(s) and auditor(s) from the Sponsor or its designee, the IRB 
and regulatory authority access to the patient’s original source records for data verification and to 
audit the data collection process. The patient’s confidentiality will be maintained and will not be 
made publicly available to the extent permitted by applicable laws and regulations. 
10.3.3 Patient Privacy 
Before enrollment into the study, the Investigator or designee must explain to each patient that 
their personal information will be shared with the Sponsor and companies working with the 
Sponsor, as well as shared with regulatory agencies and the IRB. Personal information is shared 
to ensure the study is being conducted properly, to evaluate the study results, and to develop and 
approve the study drug if it is shown to be safe and effective.  
It is the Investigator’s (or designee’s) responsibility to obtain the patient’s written 
acknowledgement or written permission to use their personal information per country-specific 
regulations. This must be obtained before initiating any study-mandated procedures or 
enrollment into the study.  
If the patient withdraws permission to use their personal information, it is the Investigator’s 
responsibility to, 1) document the patient’s request to withdraw (i.e., as a written request), 
2) ensure that no further data will be collected from the patient, and 3) ensure that the patient 
will be removed from the study. 


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11 
ADMINISTRATIVE CONSIDERATIONS 
11.1 
Quality Management 
As part of quality management based on a risk-based approach per ICH E6(R2): risk reduction 
activities may be incorporated in protocol design and implementation, monitoring plans, 
agreements between parties defining roles and responsibilities, systematic safeguards to ensure 
adherence to standard operating procedures, and training in processes and procedures.  
Predefined quality tolerance limits should be established, taking into consideration the medical 
and statistical characteristics of the variables as well as the statistical design of the trial, to 
identify systematic issues that can impact subject safety or reliability of trial results. Detection of 
deviations from the predefined quality tolerance limits should trigger an evaluation to determine 
if action is needed. 
Study sites, the study database, and study documentation will be monitored regularly and may 
be subject to a quality assurance (QA) audit during the study by the IRB and/or the Sponsor 
or its designee. In addition, inspections may be conducted by regulatory agencies at 
their discretion.  
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC 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 SOPs and the study-specific monitoring plan, the monitors will verify that the 
clinical study is conducted, data are generated, documented (recorded), and reported in 
compliance with the protocol, GCP, and the applicable regulatory requirements (e.g., Good 
Laboratory Practices, Good Manufacturing Practices).  
Upon request, the investigational site will provide direct access and allow the Sponsor (or its 
representative including monitor), IRB and regulatory authorities to review and inspect all trial 
related sites, drug storage area, study-drug stock, drug accountability records, patient charts, 
source documents, and other records related to study conduct. 
The Investigator should contact the Sponsor or their designee immediately if contacted by a 
regulatory agency regarding an inspection.  
11.2 
Study Monitoring 
The Sponsor or designee will be responsible for the monitoring of the study. Study monitors will 
contact and visit the Investigators at regular intervals throughout the study to answer study 
questions, and to systematically and independently examine all study-related activities, verify 
adherence to the protocol, and assess the completeness, consistency, and accuracy of the data.  
Monitoring may include, but is not limited to: 
• Reviewing eCRFs for accuracy and completeness. 
• Assessing compliance with the protocol and adherence to regulatory and GCP 
requirements 
• Verifying that the site maintains an adequate supply of study drugs, any necessary 
supplies, and that appropriate storage conditions are maintained. 


Protocol CORT118335-877 
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Amendment 5  |  09 June 2022 
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Page 85 
Monitoring visits will be conducted according to the ICH Guideline for GCP and all applicable 
country and local regulations and guidance. 
By agreeing to participate in this research study, the Investigators agree to co-operate with 
the study monitor to ensure that any problems detected during the monitoring visits are 
promptly resolved.  
Monitoring methods, responsibilities, and requirements will be outlined in the study 
monitoring plan. 
11.3 
Documentation 
11.3.1 Source Documentation 
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, clinic charts, the Investigator’s patient study 
files, results of diagnostic tests, including x-rays, laboratory tests and ECGs). All source data 
should be attributable, legible, contemporaneous, original, accurate, and completed. Changes 
to source data should be traceable (i.e., dated and initialed), 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.  
11.3.2 Case Report Forms 
The Investigator must generate and maintain complete, adequate, accurate, reliable, and legible 
records in a timely manner to enable full documentation of study conduct. All data entered into 
CRFs (paper or electronic) must be substantiated by and consistent with a source document.  
Discrepancies between CRFs and their respective source documents should be explained.  All 
changes in eCRF data entry at the study site will be performed by designated site personnel and 
will be in the clinical database audit trail. In the event paper CRFs are utilized, any change or 
correction to a CRF should be dated, initialed, and explained (if necessary) and should not 
obscure the original entry. 
All changes in CRF data entry at the study site will be performed by designated site personnel. 
11.3.3 Retention of Study Essential Documents 
The Investigator must retain adequate and accurate records so that study conduct can be fully 
documented and the study data to be subsequently verified.  
Study essential documents, which include the patient identification code list (i.e., patient names 
and corresponding study numbers), 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 study drug. These documents 
should be retained for a longer period, however, if required by local regulations.  


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 86 
No records will be destroyed without the written consent of the Sponsor, if applicable. If the 
Investigator can no longer maintain the records, it is the responsibility of the Investigator to 
contact the Sponsor. These documents may be transferred to another responsible party, 
acceptable to the Sponsor, who agrees to abide by the retention policies. Written notification of 
transfer must be submitted to the Sponsor. It is the responsibility of the Sponsor to inform the 
Investigator when these documents no longer need to be retained. 
11.3.4 Sample Collection, Preparation, and Shipping 
Instructions for collection, preparation, and shipping of all laboratory samples will be provided 
in the study laboratory manual. 
11.4 
Long-Term Retention of Biological Samples 
All biological samples will be retained by the Sponsor or designee under the original informed 
consent of the patient and the IRB approval. Samples will be held for a period up to 15 years 
after completion of the clinical study report. The Sponsor or the designee may store the patient’s 
sample(s) longer if required to address regulatory agency questions; in this event, the patient’s 
sample(s) will be destroyed after all questions are adequately answered.  
An individual patient can choose to withdraw consent to have his/her samples used for future 
research at any time without affecting their participation in the study, or their care by the health 
provider. After receipt of a request for sample destruction, that patient’s sample(s) will then no 
longer be used for future research purposes beyond the current study, and their sample(s) will be 
destroyed. However, if there are ongoing regulatory questions, the patient’s sample(s) will be 
destroyed after all questions are adequately answered. 
The long-term retention samples will be coded to allow de-identification according to applicable 
regulatory guidelines. It is the responsibility of the trial site to ensure that samples are 
appropriately labelled in accordance with trial procedures to comply with all applicable laws. 
Biological samples collected from participants as part of this trial will be transported, stored, 
accessed, and processed in accordance with all applicable laws relating to the use and storage of 
human tissue for research purposes. 
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/government health authorities and 
study procedures. Storage of study drug is described in Table 1. 
11.5.2 Clinical-Supply Inventory 
Each clinical site is required to complete and maintain a detailed inventory 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.  


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 87 
Unused study drug must be kept in a secure location for accountability and reconciliation by the 
study monitor. The Investigator or their designee must provide an explanation for any destroyed 
or missing study drug or study materials. 
The Investigator or their 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 their designee must retain all unused or expired study supplies 
until the study monitor (on-site clinical research associate) has confirmed the accountability data 
and Sponsor has approved return or destruction. 
11.5.3 Return or Destruction of Study Drug and/or Supplies 
At the end of the study, after final drug-inventory reconciliation by the study monitor, the study 
site will either return study drug and/or supplies to the Sponsor or designee, or destroy all unused 
study drug and/or supplies, including empty containers, according to institutional policy. 
11.5.4 Study Drug Destroyed by the Site 
Unused/undispensed study drug and/or supplies may be destroyed on site, per the site’s SOPs, 
but only after Sponsor has granted approval for drug destruction. The study monitor must 
account for all study drug in a formal reconciliation process, before study-drug destruction.  
Any destruction of study drug on site must be documented. Documentation must be provided to 
the Sponsor and retained in the Investigator study files. 
11.5.5 Study Drug Returned to Sponsor for Destruction 
If a site is unable to destroy unused/undispensed study drug and/or supplies appropriately, the 
site can request return of study drug and/or supplies to the Sponsor or designee.  
The return of study drug and/or supplies must be accounted for on a Study Drug Return Form 
provided by the Sponsor or designee 
11.5.6 Drug Accountability 
It is the responsibility of the Investigator to maintain drug accountability at the study site and 
ensure that a current record of study-drug disposition is maintained. It is the responsibility of the 
Investigator to ensure that the study drug 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, lost, or accidentally or deliberately 
destroyed study product.  
Dispensing records will document quantities received from the Sponsor (or designee) and 
quantities dispensed to patients, including lot number, date dispensed, patient identifier number, 
patient initials, the initials of the person dispensing the drug, quantities of drug returned by the 
patients and disposal/return of returned study drug.  
11.6 
Post-Trial Care 
There is no provision for continued access to study drug (Section 5.10). 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 88 
11.7 
Protocol Noncompliance  
A protocol deviation is any noncompliance with requirements in the clinical-trial protocol, GCP, 
or the manual of procedures (MOP). The noncompliance may be on the part of the patient, the 
Investigator, or the study-site staff. As a result of deviations, corrective actions consistent with 
ICH E6(R2) may be implemented.  
Prospective approval of deviations from the inclusion and exclusion criteria, known as protocol 
waivers or exemptions are not permitted. Changes to the conduct of the protocol may not be 
made, except to address an immediate risk to the subject, unless the change has been submitted 
to the regulatory authorities for review and the change has been approved by the IRB.  
Sponsor clinical-study staff and contractors may acknowledge, but not approve, protocol 
deviations reported by a site that have happened or are planned to happen.  
Any significant protocol deviations affecting patient eligibility and/or safety or data integrity 
must be submitted to the IRB and regulatory authorities, as applicable, prior to implementation.  
After the protocol is approved by the Sponsor and by IRBs, any change that might affect the 
approval of the IRBs must be documented in the form of a protocol amendment. The amended 
protocol must be approved by the IRB and annually, as local regulations require.  
11.8 
Financial Disclosure 
Investigators will be required to disclose any financial equity interests in the Sponsor and any 
conflicts of interest, as defined by the Sponsor.  
11.9 
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 the Sponsor. The Investigator agrees to submit all manuscripts or abstracts to the 
Sponsor for review before submission to the publisher. 
The Sponsor 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 (ICMJE) requirements. 
11.10 Electronic Systems 
All electronic systems, including clinical study sites, clinical operations, data management, 
biostatistics, safety, and CRO systems, etc., used to collect, manage, and store study data should 
be validated and in compliance with 21 CFR Part 11. The validation documentation should be 
made available at all times during inspection or Sponsor audits. Any modification to the 
validated system should be documented via a quality change control process and justified to their 
intended use. 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 89 
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). 2020. The American Heart Association Diet and Lifestyle 
Recommendations. Accessed June 29, 2020. https://www.heart.org/en/healthy-
living/healthy-eating/eat-smart/nutrition-basics/aha-diet-and-lifestyle-recommendations.  
Allison DB1, Casey DE. 2001. Antipsychotic-induced weight gain: a review of the literature. J 
Clin Psychiatry 62 Suppl 7:22–31. 
CDC (Centers for Disease Control and Prevention). 2020. How much physical activity do adults 
need? Accessed June 29, 2020 https://www.cdc.gov/physicalactivity/basics/ 
adults/index.htm 
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. 
Hunt HJ, Ray NC, Hynd G, Sutton J, Sajad M, O’Connor E, et al. 2012. Discovery of a novel 
non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain 
model in the rat. Bioorg Med Chem Lett. 22:7376–7380. 
Laursen TM, Munk-Olsen T, Vestergaard M. 2012. Life expectancy and cardiovascular mortality 
in persons with schizophrenia. Curr Opin Psychiatry 25(2):83–88. 
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. 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 90 
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. 
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 
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. 
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. 
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. 
 


Protocol CORT118335-877 
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Amendment 5  |  09 June 2022 
Confidential 
Page 91 
13 
APPENDICES 
 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 92 
Appendix A: Schedule(s) of Activities 
Table 9 
Schedule of Activities 
 
 
 
Treatment Period 
 
Follow-
Up  
28±5 
days 
after 
last 
dose of 
study 
drug 
Assessment 
Screening 
Days  
−28  
to −1 
Baseline 
Day 1 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
Week
10 
Week 
12 
Week 
14 
Week 
16 
Week 
18 
Week 
19 
Week 
20 
Week 
21 
Week 
22 
Week 
23 
Week 
24 
Week 
25 
Week 
26 
ET a 
Day 
15  
±2 
days 
Day 
29 
±2 
days 
Day 
43 
±2 
days 
Day 
57 
±2 
days 
Day 
71 
±5 
days 
Day 
85 
±5 
days 
Day 
99 
±5 
days 
Day 
113 
±5 
days 
Day 
127 
±5 
days 
Day 
134 
±5 
days 
Day 
141 
±5 
days 
Day 
148 
±5 
days 
Day 
155 
±5 
days 
Day 
162 
±5 
days 
Day 
169 
±5 
days 
Day 
176 
±5 
days 
Day 
183 
±5 
days 
Informed 
consent b 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Inclusion/ 
exclusion 
criteria b 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Medical history 
and prior 
medications c 
X  
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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 
X 
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 
FSH test e 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Urine drug test 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Diet and 
exercise 
counseling 
- 
X 
- 
- 
- 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 93 
 
 
 
Treatment Period 
 
Follow-
Up  
28±5 
days 
after 
last 
dose of 
study 
drug 
Assessment 
Screening 
Days  
−28  
to −1 
Baseline 
Day 1 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
Week
10 
Week 
12 
Week 
14 
Week 
16 
Week 
18 
Week 
19 
Week 
20 
Week 
21 
Week 
22 
Week 
23 
Week 
24 
Week 
25 
Week 
26 
ET a 
Day 
15  
±2 
days 
Day 
29 
±2 
days 
Day 
43 
±2 
days 
Day 
57 
±2 
days 
Day 
71 
±5 
days 
Day 
85 
±5 
days 
Day 
99 
±5 
days 
Day 
113 
±5 
days 
Day 
127 
±5 
days 
Day 
134 
±5 
days 
Day 
141 
±5 
days 
Day 
148 
±5 
days 
Day 
155 
±5 
days 
Day 
162 
±5 
days 
Day 
169 
±5 
days 
Day 
176 
±5 
days 
Day 
183 
±5 
days 
Physical 
examination f 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
Body weight g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
X 
X 
X 
Height g 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Vital signs 
(including 
orthostatic vital 
signs) 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
12-lead resting 
ECG (in 
triplicate) h  
X 
X  
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
Waist and hip 
measurements i 
- 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
Dispensing of 
study drug 
(tablets) 
- 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
Accounting of 
unused tablets 
- 
- 
X 
X 
X 
X 
X 
X 
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 
X 
- 
X 
- 
X 
- 
X 
- 
X 
X 
- 
Virus screen 
(HCV, HBV) 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 94 
 
 
 
Treatment Period 
 
Follow-
Up  
28±5 
days 
after 
last 
dose of 
study 
drug 
Assessment 
Screening 
Days  
−28  
to −1 
Baseline 
Day 1 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
Week
10 
Week 
12 
Week 
14 
Week 
16 
Week 
18 
Week 
19 
Week 
20 
Week 
21 
Week 
22 
Week 
23 
Week 
24 
Week 
25 
Week 
26 
ET a 
Day 
15  
±2 
days 
Day 
29 
±2 
days 
Day 
43 
±2 
days 
Day 
57 
±2 
days 
Day 
71 
±5 
days 
Day 
85 
±5 
days 
Day 
99 
±5 
days 
Day 
113 
±5 
days 
Day 
127 
±5 
days 
Day 
134 
±5 
days 
Day 
141 
±5 
days 
Day 
148 
±5 
days 
Day 
155 
±5 
days 
Day 
162 
±5 
days 
Day 
169 
±5 
days 
Day 
176 
±5 
days 
Day 
183 
±5 
days 
Hematology 
with platelet 
and WBC 
differential 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
X 
 X 
X 
X 
X 
 X 
X 
X 
X 
X 
Chemistry  j  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panel k 
X 
X 
- 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
 
X 
X 
X 
HbA1c 
X 
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±1 hour) l 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
X 
X 
- 
Serum cortisol  
(morning–8 
AM±1 hour) l 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
X 
X 
- 
Serum 
aldosterone l 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
X 
X 
- 
Glucocorticoid-
receptor 
activity marker 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
X 
X 
- 
MINI  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
BPRS 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 95 
 
 
 
Treatment Period 
 
Follow-
Up  
28±5 
days 
after 
last 
dose of 
study 
drug 
Assessment 
Screening 
Days  
−28  
to −1 
Baseline 
Day 1 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
Week
10 
Week 
12 
Week 
14 
Week 
16 
Week 
18 
Week 
19 
Week 
20 
Week 
21 
Week 
22 
Week 
23 
Week 
24 
Week 
25 
Week 
26 
ET a 
Day 
15  
±2 
days 
Day 
29 
±2 
days 
Day 
43 
±2 
days 
Day 
57 
±2 
days 
Day 
71 
±5 
days 
Day 
85 
±5 
days 
Day 
99 
±5 
days 
Day 
113 
±5 
days 
Day 
127 
±5 
days 
Day 
134 
±5 
days 
Day 
141 
±5 
days 
Day 
148 
±5 
days 
Day 
155 
±5 
days 
Day 
162 
±5 
days 
Day 
169 
±5 
days 
Day 
176 
±5 
days 
Day 
183 
±5 
days 
C-SSRS 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
CGI 
X 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
OWLQOL/ 
WRSM 
- 
X 
X 
X 
X 
- 
X 
- 
X 
- 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
X 
PK substudy m 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Abbreviations: ACTH, adrenocorticotropic hormone; AE, adverse event; BPRS, Brief Psychiatric Rating Scale; CGI, Clinical Global Impression; C-SSRS, Columbia-Suicide 
Severity Rating Scale; ECG, electrocardiogram; ET, early termination; FSH, follicle-stimulating hormone; HbA1c, glycated hemoglobin; ICF, informed consent form; MINI, 
Mini International Neuropsychiatric Interview; OWLQOL, Obesity Weight Loss Quality of Life Scale; PK, pharmacokinetic; T4, thyroxine; TSH, thyroid-stimulating hormone; 
WBC, white blood cell (count); WRSM, weight-related symptom measure. 
 
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. 
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. BMI will be autocalculated from the EDC database based on height and weight measurements. 
h. At Baseline, the 12-lead resting ECG (in triplicate) will be performed both before dosing and 2 hr ±15 min after dosing. 
i. Waist-to-hip ratio will be autocalculated from the EDC database based on waist and hip measurements.  
j. Fasting chemistry panels will occur at Screening, Baseline, Week 10, Week 26, and ET. All other chemistry panels will be done nonfasting.  
k. Lipid panel to include cholesterol, direct low-density lipoprotein (LDL), very-low-density LDL (VLDL) and high-density lipoprotein (HDL). Fasting lipid 
panels to include triglycerides will occur at Screening, Baseline, Week 10, Week 26, and ET.  
l. ACTH and serum cortisol tests will be completed in the morning–8 AM ±1 hour).  


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 96 
m. 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 drug on the day of their Week 4 visit in the clinic (witnessed dosing). 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 97 
Appendix B: Summary of Changes 
Significant changes in Amendment 5 of the protocol dated 09 June 2022 compared with the 
Amendment 4 dated 11 January 2022 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.  
A significant revision to the protocol is: 
• Addition of study visits at Weeks 19, 21, 23 and 25 during the treatment period to 
increase safety monitoring of remaining patients on the study for any changes in reported 
AEs, concomitant medications, and to their laboratory values. 
– Chemistry panel and hematology with platelet and WBC differential testing will be 
performed at every week at these visits. 
• For clinic visits at Weeks 20 and 24, additional laboratory testing for  
– Hematology with platelet and WBC differential 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 98 
Table 10 
Summary of Changes in Protocol CORT118335-877 Amendment 5  
Section 
Summary of 
Change 
Revisions 
Global changes  
Updated version 
and date of the 
protocol. 
Amendment 4Amendment 5 
11 January 202209 June 2022 
Cover Page 
Change in 
Medical Monitor 
 
 
 
Synopsis 
Updated synopsis 
to align with 
changes in the 
protocol body. 
-- 
3.1 Overall 
Design 
Study design 
updated to align 
with the treatment 
visits in Section 7 
and the Schedule 
of Activities. 
CORT118335-877 Study Design (Figure 3) updated. 
5.11.1 
Independent Data 
Monitoring 
Committee to 
Monitor Patient 
Safety 
Updated text to 
align with 
language in the 
IDMC Charter.  
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 
and in the conduct and monitoring of randomized clinical trials. The 
IDMC will meet at least quarterly. Further details describing the IDMC 
meeting frequency, IDMC composition, contents of data reports, 
responsibilities, and decision rules will be described in the IDMC Charter. 
6.4.1 Physical 
Examination and 
Vital Signs 
Updated text to 
align with 
assessments 
performed at 
Treatment Visits 
(Section 7 and 
Schedule of 
Activities). 
Paragraph 1:  
Physical examinations including a basic neurologic examination will be 
performed at every visit during the study and at Follow Up as indicated 
in the SoA (Appendix A). 
6.4.3 
Electrocardiogram 
Updated text to 
align with 
assessments 
performed at 
Treatment Visits 
(Section 7 and 
Schedule of 
Activities). 
Paragraph 1:  
Twelve-lead ECG tracings will be obtained in triplicate from all patients 
at every visit during the study as indicated in the SoA (Appendix A). 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 99 
Section 
Summary of 
Change 
Revisions 
6.5 Efficacy 
Assessments  
Updated text to 
align with 
assessments 
performed at 
Treatment Visits 
(Section 7 and 
Schedule of 
Activities). 
Paragraph 2:  
Body weight will be measured at every visit as indicated in the SoA 
(Appendix A). Body weight will be measured without overcoat and shoes, 
and with only light clothing. 
Paragraph 3:  
Waist circumference will be measured for all patients at every visit as 
indicated in the SoA (Appendix A). 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. 
7 Study 
Assessments and 
Procedures by 
Study Visit 
Addition of study 
visits at Weeks 
19, 21, 23 and 25 
during the 
treatment period 
to increase safety 
monitoring of 
remaining 
patients on the 
study for any 
changes in 
reported AEs, 
concomitant 
medications, and 
to their laboratory 
values. Section 
numbers were 
renumbered.   
The following study visits added: 
• 7.3.10 Week 19: Study Day 134 (±5 day) 
• 7.3.12 Week 21: Study Day 148 (±5 day) 
• 7.3.14 Week 23: Study Day 162 (±5 day) 
• 7.3.16 Week 25: Study Day 176 (±5 day) 
At all the visits added, the following assessments will be performed- 
• Record any AEs 
• Record concomitant medications 
• Perform laboratory tests: 
– 
Chemistry panel  
– 
Hematology with platelet and WBC differential 
 
7.3 Treatment 
Period 
Updated text to 
align with 
treatment visits 
and 
corresponding 
assessments. 
At all clinic visits during the Treatment Period (except Weeks 8, 12, 16, 
20, and 24), tThe following will be performed as indicated in the SoA, 
(Appendix A): 
…. 
7.3.107.3.11 
Week 20: Study 
Day 141 (±5 day) 
Added 
hematology with 
platelet and WBC 
differential 
laboratory 
assessments.  
… 
• 
Perform laboratory test 
– 
Lipid panel 
– 
Hematology with platelet and WBC differential 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 100 
Section 
Summary of 
Change 
Revisions 
7.3.127.3.15 
Week 24: Study 
Day 169 (±5 day) 
Added 
hematology with 
platelet and WBC 
differential 
laboratory 
assessments. 
… 
• 
Perform laboratory test 
– 
Lipid panel 
– 
Hematology with platelet and WBC differential 
11.3.1 Source 
Documentation 
Updated list of 
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 x-rays, laboratory tests, and ECGs). 
All source data should be attributable, legible, contemporaneous, original, 
accurate, and completed. Changes to source data should be traceable (i.e., 
dated and initialed), should not obscure the original entry, and should be 
explained, if necessary. 
11.3.2 Case 
Report Forms 
Updated text to 
account for paper 
or electronic 
CRFs. 
The Investigator must generate and maintain complete, adequate, accurate, 
reliable, and legible records in a timely manner to enable full 
documentation of study conduct. All data entered into CRFs (paper or 
electronic) must be substantiated by and consistent with a source 
document.  
Discrepancies between CRFs and their respective source documents 
should be explained. Any change or correction to a CRF should be dated, 
initialed, and explained (if necessary) and should not obscure the original 
entry. All changes in eCRF data entry at the investigator site must obtain 
Investigator or designee’s authorization. All changes in eCRF data entry 
at the study site will be performed by designated site personnel and 
will be in the clinical database audit trail. In the event paper CRFs 
are utilized, any change or correction to a CRF should be dated, 
initialed, and explained (if necessary) and should not obscure the 
original entry. 
All changes in CRF data entry at the study site will be performed by 
designated site personnel. 
11.6.111.5.1 
Inventory, 
Reconciliation, 
Return, and 
Disposition of 
Clinical Supplies 
Updated text for 
clarity. 
All study drug and related materials should be stored, inventoried, 
reconciled, and destroyed or returned according to applicable state and 
federal regulations/government health authorities and study procedures. 
Storage of study drug is described in Table 1. 
11.6.211.5.2 
Clinical-Supply 
Inventory 
Updated text to 
align with 
Corcept protocol 
template. 
Each clinical site is required to complete and maintain a detailed inventory 
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 their designee 
must provide an explanation for any destroyed or missing study drug 
or study materials.  


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 101 
Section 
Summary of 
Change 
Revisions 
The Investigator or their 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 their 
designee must retain all unused or expired study supplies until the 
study monitor (on-site clinical research associate) has confirmed the 
accountability data and Sponsor has approved return or destruction. 
11.711.5.6 Drug 
Availability 
Updated text to 
align with 
Corcept protocol 
template. 
It is the responsibility of the Investigator to maintain drug accountability 
at the study site and ensure that a current record of study-drug disposition 
is maintained. It is the responsibility of the Investigator to ensure that 
the study drug 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, 
lost, or accidentally or deliberately destroyed study product. 
Dispensing records will document quantities received from the Sponsor 
(or designee) and quantities dispensed to patients, including lot number, 
date dispensed, patient identifier number, patient initials, the initials of the 
person dispensing the drug, quantities of drug returned by the patients and 
disposal/return of returned study drug. Prior to destruction of returned 
study drug, the study monitor should confirm drug accountability, if 
allowed by local institutional policy. 
11.811.6 Post-trial 
Care  
Updated text to 
align with 
Corcept protocol 
template. 
Not applicable. There is no provision for continued access to study 
drug (Section 5.10). 
11.911.7 Protocol 
Noncompliance 
Updated text to 
align with 
Corcept protocol 
template. 
A protocol deviation is any noncompliance with requirements in the 
clinical-trial protocol, GCP, or the manual of procedures (MOP). The 
noncompliance may be on the part of the patient, the Investigator, or the 
study-site staff. As a result of deviations, corrective actions consistent 
with ICH E6(R2) may be implemented.  
Prospective approval of deviations from the inclusion and exclusion 
criteria, known as Pprotocol waivers or exemptions are not permitted. 
Changes to the conduct of the protocol may not be made, except to 
address an immediate risk to the subject, unless the change has been 
submitted to the regulatory authorities for review and the change has been 
approved by the IRB. 
Corcept Sponsor clinical-study staff and contractors may acknowledge, 
but not approve, protocol deviations reported by a site that have happened 
or are planned to happen.  
Any significant protocol deviations affecting patient eligibility and/or 
safety or data integrity must be submitted to the IRB and regulatory 
authorities, as required applicable, prior to implementation.  
After the protocol is approved by the Sponsor and by IRBs, any change 
that might affect the approval of the IRBs must be documented in the form 
of a protocol amendment. The amended protocol must be approved by the 
IRB and annually, as local regulations require. 


Protocol CORT118335-877 
Corcept Therapeutics  
Amendment 5  |  09 June 2022 
Confidential 
Page 102 
Section 
Summary of 
Change 
Revisions 
11.10 Electronic 
Systems 
Added new 
section on 
electronic 
systems to align 
with Corcept 
protocol template. 
All electronic systems, including clinical study sites, clinical 
operations, data management, biostatistics, safety, and CRO systems, 
etc., used to collect, manage, and store study data should be validated 
and in compliance with 21 CFR Part 11. The validation 
documentation should be made available at all times during 
inspection or Sponsor audits. Any modification to the validated 
system should be documented via a quality change control process 
and justified to their intended use. 
Appendix A 
Updated 
Schedule of 
Activities to align 
with changes in 
the protocol. 
Added assessments to align with visits added to Section 7. 
 

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: NCT04524403 
 
Date: 13 October 2022 


  
Miricorilant, Protocol CORT118335-877  
 Statistical Analysis Plan v1.0 | 13 October 2022 
Confidential 
Page 1 
STATISTICAL ANALYSIS PLAN (SAP) 
Title 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled 
Study Evaluating the Safety, Efficacy, and Pharmacokinetics 
of Miricorilant in Obese Adult Patients with Schizophrenia 
Taking Antipsychotic Medications (GRATITUDE II) 
Study Protocol 
CORT118335-877 
Phase  
2 
Investigational Product 
Miricorilant (CORT118335) 
Indication 
Antipsychotic-induced Weight Gain 
Protocol Version 
Amendment 5 
Protocol Version (date) 
09 June 2022 
Sponsor 
Corcept Therapeutics Incorporated 
149 Commonwealth Drive 
Menlo Park, California 94025 USA 
(650) 327-3270 
Document Author 
 
 
 
 
SAP Version / Date 
V1.0 / 13 October 2022 
 
 
 
Confidentiality Statement 
This document contains information that is the confidential and proprietary property  
of Corcept Therapeutics. Any use, distribution, or disclosure without the prior  
written consent of Corcept Therapeutics is strictly prohibited except to the  
extent required under applicable laws or regulations. 
 






  
Miricorilant, Protocol CORT118335-877  
 Statistical Analysis Plan v1.0 | 13 October 2022 
Confidential 
Page 4 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACTH 
adrenocorticotropic hormone 
AE 
adverse event 
AIWG 
antipsychotic-induced weight gain 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance  
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 
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 
EE 
efficacy evaluable 
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 
IDMC 
Independent Data Monitoring Committee 


  
Miricorilant, Protocol CORT118335-877  
 Statistical Analysis Plan v1.0 | 13 October 2022 
Confidential 
Page 5 
INR 
international normalized ratio 
ITT 
intent-to-treat 
LDL 
low-density lipoprotein 
LLOQ 
lower limit of quantification 
LOCF 
last observation carried forward 
MAR 
missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
MMRM 
mixed-effect model with repeated measures 
MR 
mineralocorticoid receptor 
NCI 
National Cancer Institute 
OWLQOL 
Obesity Weight Loss Quality of Life Scale 
PK 
pharmacokinetic 
PT 
preferred term 
REML 
restricted maximum likelihood 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SI 
Système International 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
ULN 
upper limit of normal 
ULOQ 
upper limit of quantification 
W 
week 
WHO 
World Health Organization 
WRSM 
Weight-Related Symptom Measure 
 


  
Miricorilant, Protocol CORT118335-877  
 Statistical Analysis Plan v1.0 | 13 October 2022 
Confidential 
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 ................................................................................................................................ 10 
List of Figures ............................................................................................................................... 10 
1 
INTRODUCTION ............................................................................................................ 11 
2 
STUDY OVERVIEW ....................................................................................................... 11 
2.1 
Overall Design .................................................................................................................. 11 
3 
STUDY OBJECTIVES ..................................................................................................... 12 
3.1 
Primary Efficacy Objective ............................................................................................... 12 
3.2 
Secondary Objectives........................................................................................................ 12 
3.3 
Exploratory Objectives ..................................................................................................... 12 
3.4 
Safety Objective ................................................................................................................ 13 
3.5 
Pharmacokinetic Objective ............................................................................................... 13 
4 
STUDY ENDPOINTS ...................................................................................................... 13 
4.1 
Primary Efficacy Endpoint ............................................................................................... 13 
4.2 
Secondary Efficacy Endpoints .......................................................................................... 13 
4.3 
Exploratory Endpoints ...................................................................................................... 13 
4.4 
Safety Endpoints ............................................................................................................... 14 
4.5 
Pharmacokinetic Endpoint ................................................................................................ 14 
5 
SAMPLE SIZE CONSIDERATIONS .............................................................................. 14 
6 
ANALYSIS POPULATIONS .......................................................................................... 15 
6.1 
All Enrolled Population .................................................................................................... 15 
6.2 
Safety Population .............................................................................................................. 15 
6.3 
Intent-To-Treat (ITT) Population ..................................................................................... 15 
6.4 
Modified Intent-To-Treat (mITT) Population .................................................................. 15 


  
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 Statistical Analysis Plan v1.0 | 13 October 2022 
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Page 7 
6.5 
Efficacy Evaluable (EE) Population ................................................................................. 15 
6.6 
Pharmacokinetic (PK) Analysis Population...................................................................... 15 
7 
DEFINITIONS, COMPUTATIONS AND CONVENTIONS ......................................... 15 
7.1 
Definitions......................................................................................................................... 15 
7.2 
Reporting Conventions ..................................................................................................... 16 
7.3 
Conventions for Dates....................................................................................................... 17 
7.4 
Treatment Group Presentation .......................................................................................... 17 
7.5 
Handling of Missing Data ................................................................................................. 17 
7.6 
Analysis Visit Windows ................................................................................................... 17 
8 
TIMING OF ANALYSES ................................................................................................ 18 
8.1 
Interim Analysis ................................................................................................................ 18 
8.2 
Final Analyses and Reporting ........................................................................................... 18 
9 
STATISTICAL METHODS ............................................................................................. 18 
9.1 
General Statistical Consideration ...................................................................................... 18 
9.2 
Patient Disposition ............................................................................................................ 19 
9.3 
Protocol Deviations ........................................................................................................... 19 
9.4 
Demographic and Baseline Characteristics ...................................................................... 19 
9.5 
Medical History ................................................................................................................ 20 
9.6 
Prior and Concomitant Medications and Subsequent Therapies ...................................... 20 
9.7 
Extent of Exposure and Study Drug Compliance ............................................................. 20 
9.8 
Efficacy Analyses ............................................................................................................. 21 
9.8.1 Multiplicity Adjustment for Efficacy Analyses .................................................... 21 
9.8.2 Primary Efficacy Analysis .................................................................................... 21 
9.8.2.1 Supportive Analyses .............................................................................. 23 
9.8.2.2 Sensitivity Analyses ............................................................................... 24 
9.8.3 Secondary Efficacy Analyses ............................................................................... 26 
9.8.3.1 Change from Baseline in Body Weight for Both Dose Levels of 
Miricorilant Combined vs Placebo ........................................................ 26 
9.8.3.2 Responders Achieving a  5% Weight Loss .......................................... 26 


  
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Page 8 
9.8.3.3 Waist-to-Hip Ratio ................................................................................. 27 
9.8.4 Exploratory Analyses ............................................................................................ 28 
9.8.4.1 Antipsychotic Medication Subgroup Analysis ...................................... 28 
9.8.4.2 Body Mass Index Subgroup Analysis .................................................... 28 
9.8.4.3 Homeostatic Model Assessment for Insulin Resistance ........................ 28 
9.8.4.4 Adrenocorticotropic Hormone ............................................................... 29 
9.8.4.5 Serum Cortisol ....................................................................................... 29 
9.8.4.6 Serum Aldosterone................................................................................. 29 
9.8.4.7 Brief Psychiatric Rating Scale ............................................................... 30 
9.8.4.8 Obesity Weight Loss Quality of Life Scale and Weight-Related 
Symptom Measure ................................................................................. 30 
9.8.4.9 Columbia-Suicide Severity Rating Scale ............................................... 31 
9.8.4.10 Clinical Global Impression-Severity...................................................... 31 
9.8.4.11 Clinical Global Impression-Improvement ............................................. 32 
9.8.4.12 HbA1c in Patients with Diabetes ........................................................... 32 
9.8.4.13 Fasting Blood Glucose in Patients with Diabetes .................................. 33 
9.8.4.14 Blood Pressure in Patients with High Blood Pressure ........................... 33 
9.9 
Safety Analyses ................................................................................................................. 33 
9.9.1 Adverse Events ..................................................................................................... 34 
9.9.2 Deaths ................................................................................................................... 35 
9.9.3 Clinical Laboratory Tests ...................................................................................... 35 
9.9.4 Vital Signs ............................................................................................................. 35 
9.9.5 Electrocardiograms ............................................................................................... 35 
9.9.6 Physical Examination............................................................................................ 36 
9.9.7 Pregnancy Tests .................................................................................................... 36 
9.10 
Other Exploratory Analyses .............................................................................................. 36 
9.10.1 Responders Achieving a 7% and 10% Weight Loss ........................................ 36 
9.10.2 Fasting Lipids........................................................................................................ 36 
9.11 
COVID-19 Infection ......................................................................................................... 36 
9.12 
Pharmacokinetic Analyses ................................................................................................ 36 


  
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Page 9 
10 
CHANGES FROM PROTOCOL IN STUDY CONDUCT OR STATISTICAL 
ANALYSIS PLAN ........................................................................................................... 37 
11 
REFERENCES ................................................................................................................. 37 
12 
APPENDIX ....................................................................................................................... 38 
12.1 
Imputation of Missing/Partially Missing Dates ................................................................ 38 
12.2 
Sample SAS Code ............................................................................................................. 39 
 


  
Miricorilant, Protocol CORT118335-877  
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Page 10 
List of Tables 
Table 1 
Analysis Visit Windows for Assessments .............................................................18 
Table 2 
List of Statistical Analyses of the Primary Endpoint .............................................25 
 
List of Figures 
Figure 1 
CORT118335-877 Study Design ...........................................................................12 
 
 
 


  
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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 
CORT118335-877, amendment 5, dated June 09, 2022: A Phase 2, Randomized, Double-Blind, 
Placebo-Controlled Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant 
in Obese Adult Patients with Schizophrenia Taking Antipsychotic Medications (GRATITUDE 
II). 
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 clinical study protocol 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 pharmacokinetic of miricorilant in obese patients (body mass index 
[BMI] ≥30 kg/m2) with schizophrenia currently taking olanzapine, risperidone, paliperidone, or 
quetiapine. 
The study consists of the following study periods: 
 Screening Period: up to 28 days 
 Treatment Period: Day 1 (Baseline) to Week 26 
 Follow-up Period: 4 weeks after last dose of study drug 
Patients who are eligible for participation in the study will be randomized on Day 1 in a 1:1:1 
ratio to 600 mg miricorilant, 900 mg miricorilant, or placebo, for 26 weeks of treatment.  
Patients will be encouraged to volunteer for the pharmacokinetic (PK) substudy, which will be 
conducted at the Week 4 visit. Up to 45 patients are expected to participate. In patients who 
consent to participate, blood samples for the measurement of miricorilant plasma concentrations 
will be collected according to the PK plan. 
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 
CORT118335-877 Study Design 
 
Abbreviation: PK, pharmacokinetics; W, week. 
3 
STUDY OBJECTIVES 
3.1 
Primary Efficacy Objective 
To assess the efficacy of both dose levels of miricorilant versus placebo in reversing 
antipsychotic-induced weight gain (AIWG). 
3.2 
Secondary Objectives 
 To assess the efficacy of both dose levels of miricorilant combined versus placebo in in 
reversing AIWG.   
 To assess the efficacy of miricorilant versus placebo in improving markers of 
cardiovascular risk such as waist-to-hip ratio. 
3.3 
Exploratory Objectives 
 To assess the efficacy of miricorilant versus placebo in reversing AIWG for each 
subgroup of patients taking: 
– Olanzapine 
– Risperidone or paliperidone (active risperidone metabolite) 
– Quetiapine 
 To assess the efficacy of miricorilant versus placebo in reducing insulin resistance in 
patients not treated with insulin. 
 To be assessed by patient group: 
– In all patients, change in adrenocorticotropic hormone (ACTH), serum cortisol, 
serum aldosterone, Brief Psychiatric Rating Scale (BPRS), Columbia Suicide 


  
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Severity Rating Scale (C-SSRS), Clinical Global Impression (CGI) Scale, Obesity 
Weight Loss Quality of Life Scale (OWLQOL) and Weight-Related Symptom 
Measure (WRSM). 
– In patients with diabetes, change in glycated hemoglobin (HbA1c) and fasting 
blood glucose. 
– In patients with high blood pressure, change in blood pressure. 
 To evaluate the dose-response relationship between miricorilant and change in 
body weight. 
 To evaluate the exposure-response relationship between miricorilant and change 
in body weight. 
3.4 
Safety Objective 
To assess the safety of miricorilant versus placebo. 
3.5 
Pharmacokinetic Objective 
To assess the PK of both dose levels of miricorilant. 
4 
STUDY ENDPOINTS 
4.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the change from Baseline to Week 26 in body weight for both 
dose levels of miricorilant versus placebo.   
4.2 
Secondary Efficacy Endpoints 
The following secondary endpoints will be assessed: 
 Change in body weight for both dose levels of miricorilant combined versus placebo 
from Baseline to Week 26 
 Percentage of patients achieving a 5% weight loss for miricorilant versus placebo from 
Baseline to Week 26 
 Change in waist-to-hip ratio for miricorilant versus placebo from Baseline to Week 26  
4.3 
Exploratory Endpoints 
The following exploratory endpoints will be assessed relative to Baseline:  
 Change in body weight from Baseline to Week 26 for miricorilant versus placebo in each 
subgroup of patients taking: 
– Olanzapine 
– Risperidone or paliperidone 
– Quetiapine 


  
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 Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in patients 
who are not treated with insulin. 
In all patients: 
 Changes from Baseline to Week 26 in ACTH, serum cortisol, and serum aldosterone 
(pharmacodynamic assessments)  
 Changes from Baseline to Week 26 in BPRS, C-SSRS, CGI, OWLQOL, and WRSM   
In patients with diabetes:  
 Change from Baseline to Week 26 in HbA1c  
 Change from Baseline to Week 26 in fasting blood glucose. 
In patients with high blood pressure: 
 Change from Baseline to Week 26 in blood pressure measurements. 
4.4 
Safety Endpoints 
Safety endpoints consist of the incidence of adverse events (AEs), treatment-emergent adverse 
events (TEAEs), serious TEAEs (TESAEs), and AEs leading to early discontinuation. 
Furthermore, safety endpoints include the changes in clinical laboratory tests, physical 
examinations, vital sign measurements and electrocardiogram (ECG) parameters from Baseline 
to Week 26. 
4.5 
Pharmacokinetic Endpoint 
Key PK parameters will be estimated from steady-state plasma concentrations. 
5 
SAMPLE SIZE CONSIDERATIONS 
Approximately 150 patients will be randomized 1:1:1 to 2 miricorilant treatment groups or 
placebo in this study. This sample size provides at least 90% power to detect a difference in body 
weight change of 5 kg in mean change from Baseline in body weight between either miricorilant 
treatment group or the placebo group. These calculations assume a common standard deviation 
of 6 kg and a 0.05 2-sided significance level 2-sample z-test. A drop-out rate of 40% from 
Baseline to Week 26 is assumed in this calculation.   
Power is greater if the difference in change from Baseline in body weight between treatment and 
placebo is greater than 5 kg. For example, assuming there is a dose-response relationship where 
the difference between treatment and placebo is 6 and 7 kg in the 600 and 900 mg miricorilant 
groups, respectively, power would be 97% and 99% for detecting a difference between each 
miricorilant group and placebo.  
Randomization will be stratified by the type of antipsychotic medication used (1 stratification 
factor with 3 levels). If ≥20 patients complete 26 weeks of treatment (10 patients treated with 
miricorilant and 10 patients treated with placebo) in 1 of the allowed antipsychotic medication 


  
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groups (olanzapine, risperidone or paliperidone, or quetiapine), this sample size provides 
60% power to detect a difference in body weight change of 5 kg between the miricorilant and 
placebo groups, at alpha=0.1 level for that antipsychotic medication. The sample size estimates 
have not been adjusted for multiple comparisons. 
6 
ANALYSIS POPULATIONS 
6.1 
All Enrolled Population 
The All Enrolled population comprises all enrolled patients.  
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 based on the safety population.  
6.3 
Intent-To-Treat (ITT) Population 
The ITT population comprises all patients who are randomized to the study.  
6.4 
Modified Intent-To-Treat (mITT) Population 
The mITT population comprises all patients who receive at least 1 dose of study drug. The mITT 
population contains the same patients as the safety population but will be referred to in 
sensitivity analyses of selected efficacy endpoints.  
6.5 
Efficacy Evaluable (EE) Population 
The EE population comprises 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. 
Per Section 7.6, ≥4 weeks of study drug is defined as study drug duration ≥23 days. See 
Section 9.7 for calculation of study drug duration. 
6.6 
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. 


  
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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 
randomization date, study day is calculated as (assessment date – first dose 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. Standard deviation 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.  
 Analysis and summary tables will have the analysis population sample size (i.e., number 
of patients).  
 Laboratory data will be reported using standard 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, standard 
deviation, first quartile, third quartile, median, 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 ‘< 0.0001’ and p-values that round to 1.000 will be presented as ‘1.000’.  
 Medical history and adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA version 24.0). AE severity will be evaluated using the 
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE 
v.5.0).  


  
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 Prior therapies and concomitant medications will be coded using the World Health 
Organization (WHO) Drug Dictionary 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 1 unit lower than the LLOQ or 
1 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. datetime format in SAS).  
 Dates recorded in comment fields will not be imputed or reported in any specific format.  
 Intervals that are presented in weeks will be transformed from days to weeks by using the 
following conversion formula, and rounding to 1 decimal place:  
– WEEKS = DAYS / 7  
– MONTHS = DAYS / 30.4375  
– YEARS = DAYS / 365.25 
Detailed rules for imputation of missing/partially missing dates for AEs, prior/concomitant 
medications/procedures, and schizophrenia diagnosis are provided in Section 12.1. 
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 are provided in Section 12.1. 
7.6 
Analysis Visit Windows 
In analysis of data summarized by study visit, unscheduled and early termination 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. 


  
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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 2 
2 
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 
Week 14 
93 
99 
106 
Week 16 
107 
113 
120 
Week 18 
121 
127 
134 
Week 20 
135 
141 
148 
Week 22 
149 
155 
162 
Week 24 
163 
169 
176 
Week 26 
177 
183 
200 
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 26 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. 
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 


  
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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, antipsychotic 
medication 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. 
9.2 
Patient Disposition 
Participant disposition will show the number of patients who have been enrolled, in ITT, safety 
and EE analysis populations, took study drug, discontinued treatment, discontinued from the 
study, reasons for discontinuations (including if due to Coronavirus disease 2019 [COVID-19]), 
completed 26 weeks of study treatment, completed the study, and completed the follow-up study 
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 and safety population by treatment 
group as randomized. A by-patient listing of important protocol deviations will be provided. 
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 ITT, safety and EE 
populations in listings, and summarized by treatment and overall: 
 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, weight, 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, or quetiapine), HOMA-IR score, ACTH, serum cortisol, serum 


  
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aldosterone, BPRS, C-SSRS, CGI-S, OWLQOL, WRSM, time from schizophrenia diagnosis to 
enrollment (years), and waist-to-hip ratio will be summarized. BMI will be calculated as: 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. 
9.5 
Medical History 
Medical history will be summarized for all patients in the ITT and safety populations. Frequency 
counts and percentages to summarize patients reporting medical history by system organ class 
(coded using MedDRA version 24.0 or above) and schizophrenia history will be presented.   
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 (preferred 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 the last dose date. Medications 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 ITT and safety populations. 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 descending order of incidence. 
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 on entry to the trial, prior, concomitant, and 
subsequent medications related to diabetes will be listed. Similarly, for patients with high blood 
pressure at Baseline as defined in Section 9.8.4.14, 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, 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: 


  
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 Duration of Exposure: The duration of exposure for each study drug will be presented in 
days and calculated as: 
Duration = Expected date of last dose − Date of the first dose + 1. 
Expected date of last dose will be the latest of either the last dose date or the last missed 
dose date. 
 Total Dose Received: The total dose received for each study drug will be:  
Total Dose Received = Total tablets dispensed – Total tablets returned. 
 Total Dose Expected: A subject will have an expected dose determined by the earliest 
start date and the latest end date times six tablets taken daily. For subjects 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 Dose Expected = Duration of Exposure x 6. 
 Compliance: Compliance is calculated for each study drug as: 
Compliance = (Total Dose Received/ Total Dose Expected) x 100. 
A by-patient listing including the study drug start date, study drug end date, number of pills 
taken, number of pills 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 each 
of the 2 miricorilant doses (600 mg and 900 mg) compared with placebo in reversing AIWG 
caused by an oral or injectable second-generation 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 each scheduled 
post-Baseline visit. That is the change in body weight at each visit will be assessed using an 
MMRM model with Baseline body weight as a continuous covariate; antipsychotic medication 
(olanzapine, risperidone/paliperidone, or quetiapine), randomized treatment (600 mg or 900 mg 
miricorilant, or placebo), visit, and treatment-by-visit interaction as fixed, categorical effects. 
The difference in body weight change between each of the 2 miricorilant doses (600 mg and 
900 mg) and placebo will be estimated from the model along with its 95% CI. The primary 
analysis will be performed on the EE population. 


  
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In more detail, the Baseline body weight is reported in kg and measured at the Day 1 (Baseline) 
visit and at 8 post-Baseline visits: Weeks 2, 4, 6, 10, 14, 18, 22, and 26, in patients who 
consented to any protocol versions. If the weight from the Day 1 visit is missing, then the weight 
from the screening visit will be used for the Baseline 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 weight at each post-Baseline visit. Specifically, the outcome 
variable, 𝑌𝑘𝑙, at visit 𝑘, 𝑘= 1, … , 9, for the lth patient is  
𝑌𝑘𝑙= 𝑊𝑘𝑙−𝑊𝑏𝑙 
where 𝑊𝑘𝑙 is the weight measured at visit k for the lth patient, where 𝑘= 1 is the Baseline visit, 
and 𝑊𝑏𝑙 is the Baseline 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’. 
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 26, 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 assumption is implied. 
The expected value of the primary analysis model can be written 
𝐸[𝑌𝑖𝑗𝑘𝑙] = 𝜇+ 𝛼𝑊𝑏𝑙+ 𝛽𝑖+ 𝛾𝑗+ 𝛿𝑘+ (𝛾𝛿)𝑗𝑘 
where 
 𝜇 is the overall mean 
 𝛼 is the effect of body weight at Baseline 
 𝛽𝑖, 𝑖= 1,2,3 is the effect of background antipsychotic medication (olanzapine, 
risperidone/paliperidone, or quetiapine) 
 𝛾𝑗, 𝑗= 1,2,3 is the effect of randomized treatment (600 mg miricorilant, 900 mg 
miricorilant, or placebo) 
 𝛿𝑘, 𝑘= 1, … , 9 is the effect of visit k 
 (𝛾𝛿)𝑗𝑘, 𝑗= 1,2,3; 𝑘= 1, … , 9, is the interaction between treatment j and visit k.  
There are 2 tests of hypotheses in this trial: 
1. Is there a difference in body weight change from Baseline to Week 26 (i.e., at the eighth 
post-Baseline visit) between 600 mg miricorilant and placebo. The null and alternative 
hypotheses for this question can be written, in terms of model parameters: 
𝐻0: 𝛾1 + (𝛾𝛿)1,9 − (𝛾3 + (𝛾𝛿)3,9) = 0  


  
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vs 
𝐻1: 𝛾1 + (𝛾𝛿)1,9 − (𝛾3 + (𝛾𝛿)3,9) ≠0, 
2. Is there a difference in body weight change from Baseline to Week 26 (i.e., at the eighth 
post-Baseline visit) between 900 mg miricorilant and placebo. The null and alternative 
hypotheses for this question can be written, in terms of model parameters: 
𝐻0: 𝛾2 + (𝛾𝛿)2,9 − (𝛾3 + (𝛾𝛿)3,9) = 0  
vs 
𝐻1: 𝛾2 + (𝛾𝛿)2,9 − (𝛾3 + (𝛾𝛿)3,9) ≠0. 
The analysis will be performed using SAS PROC MIXED (Section 12.2). Restricted maximum 
likelihood estimation (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 26 between each of the 2 miricorilant doses and placebo along with its 
95% confidence interval (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 the 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, first-order autoregressive, heterogeneous compound symmetry, and compound 
symmetry. 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 to be estimated. The 
compound symmetry assumes the variances are homogeneous (i.e., there is a correlation between 
2 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 26 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 each of other 7 post-Baseline visits, specifically Weeks 2, 4, 6, 10, 14, 18, 
and 22. The comparisons will be specified using linear contrasts analogous to that used to 
compare treatment groups at Week 26. The estimated difference between groups, its 95% CI, and 
its associated nominal p-value will be presented for each visit. No adjustments will be made for 
multiplicity. 


  
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In addition to model estimates, descriptive statistics, including 95% CIs, will summarize weight 
at each visit by treatment group, and weight change and percent weight change group at each 
post-Baseline visit. Statistics for any visit will be calculated from all patients who had weight 
measurements at the visit. The full set of descriptive statistics will be presented tabularly. The 
mean weight change per group and its 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 weight per treatment group over time will be produced. 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 
missing at random assumption for non-retrieved dropouts (the patients with missing body weight 
at Week 26). Retrieved dropouts are patients who discontinue study treatment before Week 26 
and return for measurement of body weight at the time of the pre-scheduled visit up to Week 26. 
Non-retrieved dropouts are patients who discontinue study treatment before Week 26 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 mITT population. Like the primary analysis, this sensitivity analysis will use 
supplied retrieved dropout data without imputation at Week 26. 
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 missing at 
random for any visit after a patient discontinues treatment. 
Moreover, for patients who do not have body weight at Week 26 (non-retrieved dropouts), their 
change in body weight from Baseline to Week 26 will be imputed with the treatment group mean 
change in body weight from Baseline to Week 26, derived from retrieved dropouts (the patients 
who return for Week 26 assessment after early treatment discontinuation). If there is no retrieve 
dropout data at Week 26 in a specific arm, then no imputation will be applied within the same 
arm.  
Lastly, following protocol amendment 3 and thereafter, body weight is collected biweekly. In 
more detail, body weight is measured at the Day 1 (Baseline) visit and at 13 post-Baseline visits: 
Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and 26. We will rerun the modified primary 
analysis model utilizing all available Baseline and post-Baseline visit data, where visit 𝑘=
1, … , 14. The analysis will be carried out in the EE population with the following options: 
1. Using retrieve dropout data with imputation for patients who do not have data at Week 26 
2. Using retrieve dropout data without imputation at Week 26 
3. Without retrieve dropout data 
The complete list of all analyses of the primary endpoint is included in Table 2. The difference 
between each of the 2 miricorilant doses and placebo in body weight change at Week 26 will be 
estimated for each sensitivity analysis. The estimated difference will be accompanied by its 95% 




  
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Sensitivity 
analysis 6 
EE 
Baseline, 
Weeks 2, 4, 6, 
8, 10, 12, 14, 
16, 18, 20, 22, 
24, and 26 
Excluded 
No imputation; 
MAR for missing 
data 
EE, efficacy-evaluable; MAR, missing at random; mITT, modified intent-to-treat. 
9.8.3 
Secondary Efficacy Analyses 
9.8.3.1 
Change from Baseline in Body Weight for Both Dose Levels of Miricorilant 
Combined vs Placebo 
For the first secondary endpoint, the 2 miricorilant dose groups will be combined into a single 
treatment group and assessed using a similar model as the MMRM for the primary analysis 
(Section 9.8.2). The other factors in the model will remain the same. The difference in body 
weight change at Week 26 between the combined miricorilant treatment groups and placebo will 
be estimated from the model along with its associated 95% CI and associated p-value. The least 
squares means for the combined treatment group and placebo at Week 26, along with their 
95% CIs, will also be estimated. 
In addition to model estimates, descriptive statistics, including 95% CIs, will summarize weight 
at each visit by treatment group, and weight change and percent weight change group at each 
post-Baseline visit. Statistics for any visit will be calculated from all patients who had 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 weight change per group and its 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 weight per treatment group over time will be 
produced. Additionally, mean percent change from Baseline in body weight for all visits will be 
presented graphically along with 95% CI (sourced from the t-distribution) for each treatment 
group and visit. 
9.8.3.2 
Responders Achieving a  5% Weight Loss  
The second secondary efficacy endpoint is the percentage of patients achieving a 5% weight 
loss from Baseline at Week 26 for each of the 2 miricorilant doses versus placebo. The endpoint 
requires calculation of the percent change in body weight from Baseline to Week 26 for each 
patient. For the lth patient, the percent change is calculated as 
𝑍𝑤𝑒𝑒𝑘 26,𝑙= 100 × (𝑊𝑤𝑒𝑒𝑘 26,𝑙− 𝑊𝑏𝑙) 𝑊𝑏𝑙
⁄
 
where 𝑊𝑤𝑒𝑒𝑘 26,𝑙 is the weight measured at Week 26 for the lth patient, and 𝑊𝑏𝑙 is the Baseline 
weight for the lth patient. 
The outcome variable will be a binary variable indicating a patient as a responder, that is whether 
the lth patient achieved a 5% weight loss from Baseline: 


  
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𝜃𝑙= {1 if 𝑍𝑤𝑒𝑒𝑘 26,𝑙 ≤−5 
0 otherwise    
. 
As with the primary analysis, a retrieved dropout approach will be used for patients who 
discontinue treatment prior to their Week 26 visit. Those patients will be asked to return for their 
Week 26 visits, and the 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 26, will be assigned as the weight measured at Week 26 when 
calculating the percent change in body weight. Otherwise, the last available weight measurement 
will be substituted for the weight measured at Week 26. 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 each of the 
2 miricorilant doses 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 
the 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. 
9.8.3.3 
Waist-to-Hip Ratio  
The third secondary efficacy endpoint is the change from Baseline in waist-to-hip ratio at 
Week 26 for each of the 2 miricorilant doses versus placebo. The waist-to-hip ratio will be 
calculated as the ratio of the circumference of the waist to the hip. The change in waist-to-hip 
ratio will be analyzed using the MMRM model described in Section 9.8.2 with Baseline waist-to-
hip ratio as a continuous covariate; antipsychotic medication (olanzapine, 
risperidone/paliperidone, or quetiapine), randomized treatment (600 mg or 900 mg miricorilant, 
or placebo), visit, and treatment-by-visit interaction as fixed, categorical effects. The difference 
between each of the 2 miricorilant doses and placebo group at Week 26 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 all observed data (including retrieved dropout data) will be used. Data for 
non-retrieved dropouts will not be imputed for the analysis of this variable. 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 each 
of other 7 visits from Week 2 through Week 22. The comparisons will be specified using linear 
contrasts analogous to that used to compare treatment groups at Week 26. The estimated 
difference between groups, its 95% CI, and its associated p-value will be presented for each visit.  


  
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Descriptive statistics will summarize the waist-to-hip ratio by treatment group for all visits and 
the 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 
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. 
9.8.4 
Exploratory Analyses 
9.8.4.1 
Antipsychotic Medication Subgroup Analysis 
Change in body weight for each of the two miricorilant doses versus placebo and combined 
miricorilant treatment group versus placebo in each subgroup of patients taking olanzapine, 
risperidone or paliperidone, and quetiapine will be analyzed.  The subgroup analysis for change 
from Baseline in body weight to each week will be conducted using MMRM. Retrieve dropout 
data will be used for patients who discontinue treatment early. Data for non-retrieve dropouts 
will not be imputed. The same MMRM model as described in Section 9.8.2 will be performed on 
each subset of patients in the EE population who are taking olanzapine, risperidone or 
paliperidone, and quetiapine. A sample of SAS code that can be used to implement the MMRM 
model is provided in the Section 12.2.   
9.8.4.2 
Body Mass Index Subgroup Analysis 
Change in body weight for each of the two miricorilant doses versus placebo will be analyzed in 
each BMI subgroup, including obesity class 1 (30-34.9 kg/m2), obesity class 2 (35-39.9 kg/m2), 
extreme obesity class 3 (≥ 40 kg/m2).  The subgroup analysis for change from Baseline in body 
weight to each week will be conducted using MMRM. Retrieve dropout data will be used for 
patients who discontinue treatment early. Data for non-retrieve dropouts will not be imputed. 
The same MMRM model as described in Section 9.8.2 will be performed on each subset of 
patients in the EE population. A sample of SAS code that can be used to implement the MMRM 
model is provided in the Section 12.2.   
9.8.4.3 
Homeostatic Model Assessment for Insulin Resistance  
HOMA-IR will be calculated for each patient at Baseline and Week 26 using the approximate 
formula (Matthews et al. 1985):  
HOMA-IR = (fasting plasma glucose (mg/dL) × fasting insulin (µU/mL))/405. 
Each of the 2 miricorilant doses will be compared to placebo on the difference in HOMA-IR 
between Week 26 and Baseline using a Wilcoxon rank-sum test on the EE population. For 
patients who discontinue early, HOMA-IR from the early termination visit or an unscheduled 
visit, if available and within the analysis visit window of Week 26, will be used in place of 
missing Week 26 results. Data for non-retrieve dropouts will not be imputed. 


  
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Descriptive statistics will summarize HOMA-IR by treatment group for all visits and the 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. 
9.8.4.4 
Adrenocorticotropic Hormone 
ACTH will be measured at Baseline and Week 26. Each of the 2 miricorilant doses compared to 
placebo will be assessed using analysis of covariance (ANCOVA) models that include the 
change in the endpoint between Baseline/Day 1 and Week 26 as the outcome variable, Baseline 
body weight as a covariate, and antipsychotic medication and randomized treatment as factors. 
The outcome variable will be the difference between ACTH at Week 26 and the ACTH value at 
Baseline. All observed data will be included in the analysis (including retrieved dropout data). 
Data for non-retrieved dropouts will not be imputed. The analysis will be performed on the EE 
population.  
The estimated least squares mean, standard error, and its associated p-value, as well as the 
estimated difference in the least squares means, its 95% CI, and its associated p-value will be 
presented. 
Descriptive statistics will summarize ACTH by treatment at Baseline/Day1 and Week 26 and the 
change from Baseline in ACTH by treatment at Week 26.  
9.8.4.5 
Serum Cortisol 
Like ACTH, serum cortisol will be measured at Baseline and Week 26. Each of the 
2 miricorilant doses will be compared to placebo on the change from Baseline in serum at 
Week 26 using the same method and model as ACTH. All observed data will be included in the 
analysis (including retrieved dropout data at Week 26). Data for non-retrieved dropouts will not 
be imputed. 
Descriptive statistics will summarize serum cortisol by treatment at Baseline/Day 1 and Week 26 
and the change from Baseline in serum cortisol by treatment at Week 26.  
9.8.4.6 
Serum Aldosterone 
Serum aldosterone will be measured at Baseline and Week 26. Each of the 2 miricorilant doses 
will be compared to placebo on the change from Baseline in serum aldosterone at Week 26 using 
the same method and model as ACTH. All observed data will be included in the analysis 
(including retrieved dropout data at Week 26). Data for non-retrieved dropouts will not be 
imputed. 
Descriptive statistics will summarize serum aldosterone by treatment at Baseline/Day 1 and 
Week 26, and the change from Baseline in serum aldosterone by treatment at Week 26.  


  
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9.8.4.7 
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 each of the 2 miricorilant doses and placebo. The 
outcome variable will be the difference between the total BPRS score at each post-Baseline visit 
and the total BPRS value at Baseline. Retrieve dropout data will be used for patients who 
discontinue treatment early. Data for non-retrieve dropouts will not be imputed. The analysis will 
be performed on the EE population. 
A linear contrast will estimate the difference between each of the 2 miricorilant doses and 
placebo in the change in BPRS total score at Week 26. 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 each post-Baseline visit. The mean 
change from Baseline in BRPS 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 from 
MMRM on the y-axis. 
9.8.4.8 
Obesity Weight Loss Quality of Life Scale and Weight-Related Symptom 
Measure  
Health-related quality of life scores will be measured using self-reported OWLQOL 
questionnaire and WRSM. Both the OWLQOL and the WRSM are intended to be administered 
together. The 17-item OWLQOL measures behavior and feelings that are associated with obesity 
and weight loss using a 7-point response scale that ranges from 0 “not at all” to 6 “a very great 
deal”. The WRSM is a 20-item measure of the symptoms associated with obesity and obesity 
treatment, along with the degree to which each symptom “bothers the individual”. The 
questionnaires will be completed from Baseline until Follow-up and should always be conducted 
prior to dosing when conducted on study drug administration days. 
The change from Baseline in the OWLQOL total score and the WRSM total score will use the 
MMRM analysis as described in Section 9.8.2 to assess the difference between each of the 
2 miricorilant doses and placebo. The outcome variable will be the difference between the total 
score at each post-Baseline visit and the total score at Baseline. The analysis will be performed 
on the EE population for each questionnaire separately. Retrieve dropout data will be used for 
patients who discontinue treatment early. Data for non-retrieve dropouts will not be imputed. 


  
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A linear contrast will estimate the difference between each of the 2 miricorilant doses and 
placebo in the change in the total score at Week 26. 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 OWLQOL and WRSM total scores by treatment at each 
visit and the change from Baseline in the total scores by treatment at each post-Baseline visit for 
each questionnaire separately. The mean change from Baseline in the OWLQOL and WRSM 
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 from MMRM on the y-axis. 
9.8.4.9 
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 
(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 and 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. 
9.8.4.10 
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. CGI-S will be measured at Baseline. 


  
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Descriptive statistics will summarize the CGI-S score at Baseline. 
9.8.4.11 
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 
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 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 each of the 2 miricorilant doses and placebo at Week 26. 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. 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-I score by treatment at each visit.  
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.  
9.8.4.12 
HbA1c in Patients with Diabetes 
The analysis described here will be performed on the subset of patients in the EE population who 
have diabetes on entry to the trial. Measurements of HbA1c will be obtained at screening, 
Baseline/Day 1, Week 14, and Week 26. Miricorilant (600mg and 900mg) will be compared to 
placebo on the difference in HbA1c between Week 26 and Baseline using pairwise Wilcoxon 
rank-sum tests. All observed data for HbA1c will be used in the analysis (including retrieved 
dropout data). Non-retrieved dropout data for Week 26 will not be imputed. 
Descriptive statistics will summarize HbA1c by treatment at Baseline and Week 26 and the 
change from Baseline in HbA1c by treatment at Week 26. 
Similarly, descriptive statistics and Wilcoxon rank-sum test will be provided separately for 
patients with an HbA1c < 6.5%, 6.5% ≤ HbA1c < 8.0%, and an HbA1c ≥ 8.0% at Baseline 
regardless of whether the patient has diabetes on entry to the trial, assuming at least 10 patients 


  
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per group.  If there are less than 10 patients for a given group, then only descriptive statistics will 
be provided for that group. 
9.8.4.13 
Fasting Blood 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 on entry to the trial and have 
fasting blood glucose measurements at Baseline and Week 26. Each of the 2 miricorilant doses 
will be compared to placebo on the difference in fasting blood glucose between Week 26 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 analysis window of Week 26 as outlined in Section 7.6, will be used in 
place of missing Week 26 results. Data from non-retrieved dropouts will not be imputed. 
Descriptive statistics will summarize fasting blood glucose by treatment at Baseline and Week 
26 and the change from Baseline in fasting blood glucose by treatment at Week 26. 
9.8.4.14 
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 et al. 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 systolic blood pressure (SBP) and diastolic blood pressure (DBP), will be 
measured at every visit. Descriptive statistics will summarize SBP and DBP 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 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.  


  
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9.9.1 
Adverse Events 
TEAEs are defined as those AEs with onset after the first dose of study drug or existing events 
that worsened after the first dose during the study and up to 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 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. 
Summaries that are displayed by system organ class (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 
 Summary of TEAEs leading to dose interruption 
 Summary of TEAEs related to study drug leading to dose interruption 
 Summary of TEAEs leading to dose discontinuation 
 Summary of TEAEs related to study drug leading to dose discontinuation 
 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 5.3.2) 
All above summaries will be presented by PT, by PT nested within SOC, and by maximum 
severity.  TEAEs and TESAEs 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 treatment arm and individual 
patient, including dates of onset and resolution and associated study day, duration, serious, NCI-
CTCAE grade (CTCAE v.5.0), action taken, outcome, and relationship to study drug. TESAEs 
and TEAEs leading to discontinuation will also be listed separately. 


  
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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. 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, 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 (below 
normal, normal, above normal) to lowest and to highest 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), alkaline phosphatase (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, ALP and 
gamma-glutamyl transferase (GGT), the mean and 95% CI (sourced from t-distribution) 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 SBP and DBP, heart rate, respiratory rate, and 
body temperature, will be summarized. Descriptive statistics will be presented for results, as well 
as change from Baseline to the last post-Baseline value 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. 


  
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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.  
9.10 
Other Exploratory Analyses 
Additional exploratory efficacy/safety analyses will be conducted as deemed necessary. 
9.10.1 Responders Achieving a 7% and 10% Weight Loss 
A responder is defined as a patient achieving 7% and 10% weight loss, respectively, and will 
be determined as described in Section 9.8.3.2. Similar to the secondary efficacy endpoint, the 
binary responder outcome will be analyzed using a logistic regression model as described in 
Section 9.8.3.2. A sample of SAS code that can be used to implement the logistic regression 
model is provided in the Section 12.2. 
9.10.2 Fasting Lipids 
Fasting lipids (triglycerides, low-density lipoprotein [LDL], high-density lipoprotein [HDL], 
total cholesterol) will be summarized by visit using the safety population. 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. 
9.11 
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 
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. 
9.12 
Pharmacokinetic Analyses 
PK endpoints and analysis methods will be described in a separate PK Analysis Plan that will be 
finalized before the database lock. 


  
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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, the protocol specifies that CGI-S will be analyzed using MMRM. However, CGI-S is 
only collected at Baseline. Therefore, CGI-S will be summarized descriptively at Baseline. 
11 
REFERENCES 
Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner RC. Homeostasis model 
assessment: insulin resistance and beta-cell function from fasting plasma glucose and 
insulin concentrations in man. Diabetologia. 1985;28(7):412–19. 
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 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-
Suicide Severity Rating Scale: initial validity and internal consistency findings from three 
multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266–77. 
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, 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. 2018;71(6):1269–1324 


  
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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 adverse event 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 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 26; 
  estimate 'Miricorilant - Placebo at Week 26'  
    treat 1 -1  
    treat*visit 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 -1 /cl; *diff at Wk 
26; 
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 9.8.3.2.