Clinical trial NCT03823703
Conditions: Nonalcoholic Steatohepatitis (NASH)
Keywords: Nonalcoholic Steatohepatitis NASH Nonalcoholic Fatty Liver Disease
Sponsor: Corcept Therapeutics
Start date: 2020-11-04; Completion date: 2021-04-05
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase 2, double blind, placebo-controlled, randomized study is to assess the safety and efficacy of miricorilant (CORT118335) in patients with presumed Nonalcoholic Steatohepatitis (NASH).

Detailed description:
This is a randomized, double-blind, placebo-controlled study that assessed the safety efficacy and pharmacokinetics (PK) of miricorilant in patients with presumed Nonalcoholic Steatohepatitis (NASH). Patients who meet the criteria for Study CORT118335-860 were randomized on Day 1 to receive 900 mg miricorilant, 600 mg miricorilant, or placebo for 12 weeks.

Due to observations related to safety, the study was terminated prior to completion and study objectives, endpoints, and procedures were modified as specified in the protocol.

Arms: arm 1: Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily. arm 2: Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily. arm 3: Participants received 6 placebo tablets orally once daily.
Interventions: intervention 1: Miricorilant intervention 2: Placebo
Intervention descriptions: intervention 1: Tablets taken orally intervention 2: Placebo tablets

Protocol documents:
Prot_000.pdf: 
 Title: A Phase 2a, Randomized, Double-Blind, 
 Placebo-Controlled Study Evaluating the Safety, Efficacy, and 
 Pharmacokinetics of Miricorilant in Patients with Presumed 
 Nonalcoholic Steatohepatitis (NASH) 
 NCT Number:  NCT03823703 
 Date of Original Protocol: 1 July 2020 


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CLINICAL STUDY PROTOCOL CORT118335-860 
Title 
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled 
Study Evaluating the Safety, Efficacy, and Pharmacokinetics 
of Miricorilant in Patients with Presumed Nonalcoholic 
Steatohepatitis (NASH) 
Investigational Product 
Miricorilant 
Medical Monitor 
 
 
 
Sponsor 
Corcept Therapeutics Incorporated 
149 Commonwealth Drive 
Menlo Park, California 94025 US 
(650) 327-3270 
Version 
Amendment 2 
Date 
07 December 2020 
 
 
 
 
Good Clinical Practice Statement 
This study will be conducted in compliance with the protocol, the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for 
Good Clinical Practice, and with the ethical principles contained in the Declaration of Helsinki, or 
with the laws and regulations of the country in which the research is conducted, whichever provides 
greater protection of the human study participants. Compliance with these standards provides 
assurance that the rights, safety, and well-being of study participants are protected. 
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. 
 




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Protocol Synopsis 
Name of Sponsor 
Corcept Therapeutics  
Name of Active Ingredient 
Miricorilant 
Study Number 
CORT118335-860  
Title of Study  
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Efficacy, 
and Pharmacokinetics of Miricorilant in Patients with Presumed Nonalcoholic Steatohepatitis (NASH) 
Study Centers  
Approximately 15 sites in the US  
Phase of Development 
Phase 2a 
Study Objectives 
Primary Efficacy 
• To assess the efficacy of both dose levels of miricorilant versus placebo in reducing liver 
fat content.  
Secondary Efficacy 
• To assess the efficacy of both dose levels of miricorilant combined versus placebo in reducing 
liver fat content. 
• To assess the efficacy of miricorilant versus placebo on change in biomarkers of NASH 
disease activity.  
Exploratory 
• To be assessed by patient group: 
­ In all patients, change in adrenocorticotropic hormone (ACTH), serum cortisol, serum 
aldosterone, absolute body weight, and insulin resistance. 
­ In patients with diabetes, change in glycated hemoglobin A1c (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 liver fat content. 
• To evaluate the exposure-response relationship between miricorilant and change in liver 
fat content. 
Safety 
• To assess the safety and tolerability of miricorilant versus placebo. 
Pharmacokinetic (PK) 
• To assess the PK of both dose levels of miricorilant. 
Population 
Patients with presumed NASH. 
Number of Patients Planned 
Approximately 120 patients will be enrolled in the study. 


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Methodology 
This is a Phase2a, randomized, double-blind, placebo-controlled study conducted in 120 patients with 
presumed NASH, based on blood tests and noninvasive measures, to evaluate the safety, tolerability, 
PK, and preliminary efficacy of miricorilant. (Figure S1). 
Figure S1 
CORT118335-860 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 12 weeks of treatment. Randomization will 
be stratified by the presence or absence of diabetes (see Section 3.6). 
Blood samples for the measurement of miricorilant plasma concentrations will be collected at Week 6 
according to the PK plan. 
Duration of Treatment and Duration of Study  
The maximum expected duration of a patient’s participation is 22 weeks consisting of the following 
study periods: 
• Screening Period: Up to 6 weeks 
• Treatment Period: Day 1 (Baseline) to Week 12 
• Follow-up Period: 4 weeks after last dose of study drug 
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 ≤75 years old. 
• Have a diagnosis of presumed NASH with fibrosis defined as meeting all of the following 
criteria: 
a. Either:  
(i) A historical liver biopsy within 1 year of Screening showing NASH, NAFLD Activity 
Score (NAS) ≥4, and F1 to F3 fibrosis  
OR  
(ii) The following two criteria based on non-invasive measurements: 


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Aspartate aminotransferase (AST) >17 U/L for women and AST >20 U/L for men
AND
FibroScan liver stiffness measurement ≥8.5kPa and Controlled Attenuation
Parameter (CAP) ≥300 dB/m in the 3 months prior to Screening or at Screening
b.
MRI-PDFF with ≥10% steatosis
c.
Presence of 2 or more components of metabolic syndrome: type 2 diabetes treatment or
fasting blood glucose ≥126 mg/dL, BMI ≥30 kg/m2, hypertension treatment or blood
pressure ≥130/85, history of dyslipidemia, or waist circumference ≥102 cm (40 in) in men
and ≥88 cm (35 in) in women
• Must have consistent alanine aminotransferase (ALT) and AST Baseline measurements,
established by 2 samples obtained at least 4 weeks and no more than 6 months apart. At least
one of the values must be derived from Screening safety labs; historical results within 6 months
of Screening may be used to provide the second value for eligibility. Unless both samples are
≤1.5×the upper limit of normal (ULN), to be eligible for study entry, the difference between the
first and second measurement of ALT and AST should be ≤50%. A third sample may be
repeated if the variability between the first 2 values exceeds the 50% limit. If the third sample
exceeds the 50% limit (compared with the first result), the patient is not eligible.
• Patients who are taking lipid-modifying therapies must be on stable doses for at least 3 months
prior to Screening and unlikely to change the dose during the study (for patients taking statin
medications, please see additional restrictions in exclusion criterion #15).
Key Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible to participate in the study: 
• Women who are pregnant, planning to become pregnant, or are lactating.
• Have a BMI <18 kg/m2.
• Are currently using any medications prohibited due to the potential for drug-drug interactions
(MI) with study treatments Prohibited medications (see Section 5.4.3) must be discontinued at 
least 5 half-lives prior to a patient receiving their first study treatment. Administration of 
concomitant medications (see Section 5.4) are at the discretion of the Investigator and/or the 
Corcept Medical Monitor.
• Have had successful weight-loss surgery prior to Screening or are planning weight-loss surgery 
during the study*.
*Patients who have had Roux-en-Y gastric bypass surgery or other surgical procedures that have a 
fundamentally altered gastrointestinal tract may not participate regardless of success of the procedure.
• Have any elective surgery planned during the study.
• Have significant alcohol consumption, defined as more than 2 drink units per day (equivalent to 
20 g of ethanol) in women and 3 drink units per day (equivalent to 30 g of ethanol) in men for 
≥3 consecutive months within 1 year prior to Screening, inability to reliably quantify alcohol 
intake, or score a value ≥8 on the Alcohol Use Disorders Identification Test (AUDIT) 
questionnaire.
• Use of drugs associated with NAFLD (e.g., amiodarone, methotrexate, oral or intravenous 
glucocorticoids, at supraphysiological doses (prednisone equivalent ≥5 mg/day), tamoxifen, 
estrogens at doses greater than those used for hormone replacement or contraception, anabolic 
steroids, or valproic acid) for more than 4 weeks in the 2 months prior to randomization.
• Have been treated with obeticholic acid, ursodeoxycholic acid (Ursodiol® and Urso®), 
pioglitazone or high-dose vitamin E (>400 IU/day) within the 3 months prior to Screening 
imaging studies.
• Have had liver transplantation or plan to have liver transplantation during the study.


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• Have type 1 diabetes.  
• Have type 2 diabetes and: 
­ An HbA1c ≥9.5%. 
­ Have had an insulin dose adjustment >10% within 60 days prior to enrollment. 
­ Have a requirement for glucagon-like peptide analogue (unless on a stable dose ≥3 months 
prior to Screening), a requirement for sodium/glucose cotransporter 2 (SGLT2) inhibitors 
(unless on a stable dose ≥3 months prior to Screening), or 3 or more oral anti-diabetic 
(OAD) agents (unless the OAD is stable and HbA1c <8%). 
­ Have a history of severe hypoglycemia (symptomatic hypoglycemia requiring outside 
assistance to regain neurologic status). 
• Are currently taking a statin other than stable doses of the following: lovastatin (up to 20 mg), 
pravastatin, pitavastatin, simvastatin (up to 10 mg), atorvastatin (up to 20 mg), or fluvastatin (up 
to 20 mg). A stable dose is defined as no changes in the dose in the last 3 months prior to 
Screening.  
• Are currently on the oral antidiabetic drug nateglinide (Starlix). 
Patients currently taking the medication may participate in the study if it is 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. 
• Are currently using a medication such as digoxin with an increased risk for toxicity in the event 
of electrolyte changes. 
• Have weight loss of greater than 10% within the last 6 months prior to Screening. 
• Have abnormal screening laboratories: 
a. AST >5× upper limit of normal (ULN) 
b. ALT >5× ULN  
c. Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 
d. Creatine kinase >3×ULN 
• Have known or suspected cirrhosis based on the opinion of the Investigator. The list below 
represents possible signs of suspected cirrhosis: 
a. Physical exam findings: 
i. Jaundice 
b. Laboratory findings 
i. Direct bilirubin >0.3 (except for patients who have Gilbert’s syndrome) 
ii. Platelet count <140,000/µL 
c. Imaging: 
i. Evidence of portal hypertension (dilated portal vein, presence of varices) 
ii. Evidence of a nodular liver with splenomegaly 
d. Endoscopy:  
i. Evidence of esophageal varices 
• Have hepatic decompensation defined as the presence of any of the following:  
­ Serum albumin <3.5 g/dL 
­ International normalized ratio (INR) >1.3 (unless due to therapeutic anticoagulants) 
­ Total bilirubin >1.3 mg/dL (except for patients who have Gilbert’s syndrome) 
­ History of esophageal or gastric variceal bleedings, ascites, or hepatic encephalopathy 
• Have any other chronic liver disease: 


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­ Hepatitis B as defined by presence of hepatitis B surface antigen 
­ Hepatitis C as defined by presence of hepatitis C virus (HCV) antibody and positive HCV 
RNA. Documented cured HCV infection is acceptable if >3 years from Screening visit 
­ History of current active autoimmune hepatitis  
­ History or evidence of primary biliary cholangitis 
­ History or evidence of primary sclerosing cholangitis 
­ History or evidence of Gilbert’s syndrome if direct bilirubin is elevated (in addition to total 
bilirubin ≥2) or evidence of hemolysis contributing to elevated total bilirubin 
­ History or evidence of Wilson’s disease  
­ History or evidence of alpha-1-antitrypsin deficiency  
­ History or evidence of hemochromatosis 
­ History or evidence of drug-induced liver disease, as defined on the basis of typical exposure 
and history 
­ Known bile duct obstruction 
­ Suspected or proven liver cancer 
­ Any other type of liver disease other than NASH 
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.  
• 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.  
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 
Relative change from Baseline to Week 12 in liver fat content assessed by magnetic resonance 
imaging–proton density fat fraction (MRI-PDFF) for both dose levels of miricorilant versus placebo. 
Secondary Efficacy Endpoints 
The following endpoints will be assessed relative to Baseline: 
• Change in liver fat content assessed by MRI-PDFF for both dose levels of miricorilant combined 
versus placebo. 
• Proportion of patients achieving a relative reduction in liver fat content of ≥30% by MRI-PDFF 
for miricorilant versus placebo. 
• Absolute change in liver fat content by MRI-PDFF for miricorilant versus placebo. 
• Change in AST, ALT, and gamma-glutamyl transferase (GGT) for miricorilant versus placebo. 
• Change in propeptide of type III collagen (pro-C3) for miricorilant versus placebo. 
• Change in enhanced liver fibrosis (ELF) score and its components (hyaluronic acid, tissue 
inhibitor of metalloproteinases-1 [TIMP-1], type III procollagen [PIIINP]) for miricorilant 
versus placebo. 
Exploratory Endpoints 
The following endpoints will be assessed relative to Baseline: 
• Proportion of patients achieving a relative reduction in liver fat content of ≥50% by MRI-PDFF 
for miricorilant versus placebo. 


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• Proportion of patients with complete resolution of fatty liver by MRI-PDFF for miricorilant 
versus placebo.  
In all patients: 
• Change in ACTH, serum cortisol, and serum aldosterone (pharmacodynamic assessments). 
• Change in absolute body weight.  
• Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).  
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 measurements. 
• Changes from Baseline in ECG parameters. 
Pharmacokinetic Endpoints 
• Key PK parameters estimated from steady-state plasma concentration. 
Statistical Methods 
Statistical Analyses 
Analysis of the Primary Efficacy Endpoints 
Each dose of miricorilant will be compared with placebo on the key efficacy endpoint: the relative 
change from Baseline in LFC assessed by MRI-PDFF, where relative change is defined as 100 × (LFC 
at Week 12–LFC at Baseline)/LFC at Baseline. The primary analysis will use a nonparametric, rank 
analysis of covariance (ANCOVA) that incorporates Baseline LFC as a covariate; treatment group 
(2 dose levels of miricorilant and placebo) and diabetes status (stratification factor) as factors; and rank 
relative change in LFC as the response variable. P-values for the comparisons of each miricorilant dose 
group to placebo will be derived from linear contrasts. The Hodges-Lehmann method will be used to 
estimate the median differences between groups and their 95% confidence intervals (CIs). P-values 
from the comparisons will not be adjusted for multiplicity.  
A sensitivity analysis of the primary endpoints will be performed that requires fewer assumptions than 
the primary analysis. The sensitivity analysis will employ 2 Wilcoxon rank-sum tests to compare each 
of the miricorilant dose groups to placebo; that is, one test will compare 600 mg miricorilant to placebo 
and another will compare 900 mg miricorilant to placebo.  
The relative change in LFC in each treatment group will be summarized by the median and 25th and 
75th percentiles. The primary analysis will be performed on the Efficacy Evaluable (EE) population, 
which includes all patients who receive at least 1 dose of study drug and remain in the trial for at least 
6 weeks.  
Analysis of the Secondary Efficacy Endpoints 
The secondary efficacy endpoints will be analyzed using the EE Population unless otherwise specified. 
A rank ANCOVA similar to the primary analysis will be used to test for evidence of a dose-response 
among the 2 miricorilant dose levels. Like the primary analysis, the model will include Baseline LFC 
as a covariate, diabetes status as a factor, and rank relative change in LFC as the response variable. But 


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in contrast to the primary analysis, the dose-response model will not include the placebo group; that is, 
the treatment factor will include only the 2 dose levels of miricorilant. The two miricorilant dose 
groups will be compared to each other using linear contrasts. The Hodges-Lehmann method will be 
used to estimate the median difference between the dose levels and its 95% CI. A significant difference 
between groups will be taken as evidence of a dose-response relationship. Dose-response will also be 
assessed graphically using boxplots of the relative change in MRI-PDFF for each treatment group. 
A set of 3 Cochran-Mantel-Haenszel (CMH) tests–one for each pairwise comparison of treatment 
groups – will be used to evaluate the secondary endpoint of the proportion of patients achieving a 
relative reduction in LFC of ≥30% by Week 12. Each CMH test will be stratified by diabetes status. A 
p-value will be reported for each test along with an estimate of the common relative risk of achieving a 
≥30% reduction in LFC. Each relative risk estimate will be accompanied by a 95% CI. The percentage 
of patients in each group who achieve a ≥30% reduction in LFC will be presented along with a 95% CI. 
The absolute change in LFC from Baseline to Week 12 will be assessed using a parametric ANCOVA 
model with Baseline LFC as a covariate, diabetes status and treatment group as factors, and the 
arithmetic difference between LFC at Week 12 and Baseline as the response variable. Linear contrasts 
from the model will compare each of the 2 dose levels of miricorilant to placebo. A similar ANCOVA 
that excludes the placebo group will be used to assess dose-response in absolute LFC change. A linear 
contrast from the model will compare the 2 doses of miricorilant to each other. The least squares means 
and associated confidence intervals derived from each model will be reported. 
Other continuous secondary endpoints that are measured more than once during treatment will be 
analyzed using linear mixed models for repeated measures (MMRM). These endpoints include the 
change in AST, ALT, GGT, pro-C3, and ELF score and each of its components (TIMP-1, PIIIN, and 
hyalauronic acid). Restricted maximum likelihood (REML) estimation will be used. Each MMRM 
model will include Baseline LFC as a covariate; treatment, diabetes status, visit, and treatment by visit 
interaction as fixed effects; and patient within treatment group as a random effect. Comparisons of each 
miricorilant group to placebo and to each other will be based on the estimates from the model. 
Analyses of Exploratory Endpoints 
The proportion of subjects achieving a relative reduction in LFC of ≥50%, and the proportion with a 
complete resolution, will be analyzed using CMH tests analogous to those used to evaluate the 
secondary endpoint of the proportion of patients achieving a relative reduction of ≥30%.  
Analyses of continuous endpoints, such as the change in ACTH, serum cortisol, and serum aldosterone 
from Baseline to Week 12, will be analyzed using parametric ANCOVA models with Baseline LFC as 
a covariate, diabetes status and treatment group as factors, and the arithmetic difference between the 
endpoint at Week 12 and Baseline as the response variable. Changes in HbA1c and fasting blood 
glucose within patients with diabetes will employ pairwise Wilcoxon rank-sum tests to compare 
treatment groups. A similar strategy will be used to compare groups on the change from Baseline in 
blood pressure among patients with high blood pressure. 
Exploratory analyses will be described in the SAP finalized before database lock.  
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. 


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Pharmacokinetic Analysis 
The PK data obtained, 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 approximately 40 patients/group or approximately 120 subjects randomized 
1:1:1 across 2 miricorilant treatment groups and one placebo group. The sample size calculation 
assumes that the SD for change in LFC due to treatment will be comparable to that observed in Patel et 
al. 2016, where an SD of 33% was reported, and in Harrison et al. 2019, where the SD was not reported 
but can be estimated from confidence intervals to be about 28%. A slightly more conservative estimate 
of 35% is assumed for the calculation here. Assuming that placebo patients experience a reduction in 
LFC of 10%, 34 patients per group affords 80% power to detect a significant difference at the α=0.05 
level between either miricorilant dose group and placebo as long as the miricorilant group achieves a 
35% or greater reduction in LFC. Assuming that up to 10% of patients may drop out prior to the Week 
12 MRI-PDFF assessment, the required sample size increases to 38 patients per group or 114 total 
patients. The sample size has been rounded up to 40 patients per group, or 120 total patients, for 
convenience. The sample size estimate has not been adjusted for multiple comparisons. 
 


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Contents 
CLINICAL STUDY PROTOCOL CORT118335-860 .................................................................. 1 
Sponsor Signature Page .................................................................................................................. 2 
Protocol Synopsis............................................................................................................................ 3 
Contents ........................................................................................................................................ 11 
List of Tables ................................................................................................................................ 18 
List of Figures ............................................................................................................................... 18 
List of Abbreviations and Definitions........................................................................................... 19 
1 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE ............................................................................................. 21 
1.1 
Therapeutic Area ............................................................................................................... 21 
1.1.1 Background ........................................................................................................... 21 
1.1.2 Therapeutic Hypothesis ........................................................................................ 22 
1.2 
Miricorilant: A Mixed Agonist/Antagonist of the Glucocorticoid-Receptor and Antagonist 
of the Mineralocorticoid-Receptor .................................................................................... 23 
1.2.1 Nonclinical Summary ........................................................................................... 23 
1.2.1.1 Pharmacology Related to Mode of Action ............................................. 23 
1.2.1.2 Absorption, Distribution, Metabolism, and Elimination ....................... 23 
1.2.1.3 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 Dose Regimen ............................................................... 30 
1.4.1 Design Considerations .......................................................................................... 30 
1.4.2 Rationale for Dose Selection and Regimen .......................................................... 30 
1.5 
Benefits and Risks............................................................................................................. 31 
2 
OBJECTIVES ................................................................................................................... 32 
2.1 
Primary Efficacy Objective ............................................................................................... 32 


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2.2 
Secondary Efficacy Objectives ......................................................................................... 32 
2.3 
Exploratory Objectives ..................................................................................................... 32 
2.4 
Safety Objectives .............................................................................................................. 32 
2.5 
Pharmacokinetic Objective ............................................................................................... 32 
3 
STUDY DESIGN.............................................................................................................. 33 
3.1 
Overall Design .................................................................................................................. 33 
3.2 
Study Endpoints ................................................................................................................ 33 
3.2.1 Primary Efficacy Endpoint ................................................................................... 33 
3.2.2 Secondary Efficacy Endpoints .............................................................................. 34 
3.2.3 Exploratory Endpoints .......................................................................................... 34 
3.2.4 Safety Endpoints ................................................................................................... 34 
3.2.5 Pharmacokinetic Endpoints .................................................................................. 35 
3.3 
Number of Patients and Study Participation ..................................................................... 35 
3.3.1 Number of Patients ............................................................................................... 35 
3.3.2 Duration of Patient Participation .......................................................................... 35 
3.4 
Definitions: Enrollment, Study Completer, End of Treatment, and End of Study ........... 35 
3.4.1 Enrollment............................................................................................................. 35 
3.4.2 Study Completer ................................................................................................... 35 
3.4.3 End of Treatment .................................................................................................. 35 
3.4.4 End of Study ......................................................................................................... 35 
3.5 
Study Termination by Sponsor ......................................................................................... 35 
3.6 
Diagnosis of Diabetes ....................................................................................................... 36 
4 
STUDY POPULATION ................................................................................................... 37 
4.1 
Inclusion Criteria .............................................................................................................. 37 
4.2 
Exclusion Criteria ............................................................................................................. 38 
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 ................................................................... 41 
4.5 
Replacement of Patients .................................................................................................... 42 


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4.6 
Restrictions/Requirements/Recommendations During Study ........................................... 42 
4.6.1 Dietary Restrictions .............................................................................................. 42 
4.6.2 Alcohol .................................................................................................................. 42 
4.6.3 Activity ................................................................................................................. 42 
4.6.4 Childbearing Potential and Contraception ............................................................ 42 
4.6.5 Sperm Donation: ................................................................................................... 43 
5 
STUDY TREATMENTS AND MANAGEMENT .......................................................... 44 
5.1 
Description of Study Drug, Dose, and Administration ..................................................... 44 
5.1.1 Description of Study Drug .................................................................................... 44 
5.1.2 Administration of Study Drug .............................................................................. 44 
5.2 
Non-Investigational Medicinal Agent ............................................................................... 45 
5.3 
Dose Modification ............................................................................................................ 45 
5.3.1 Dose Reduction ..................................................................................................... 45 
5.3.2 Dose Interruption and/or Discontinuation: General Criteria ................................ 45 
5.3.3 Dose Interruption and/or Discontinuation: Special Safety Events ....................... 45 
5.3.4 Pharmacokinetic Criteria for Dose Adjustment or Discontinuation ..................... 50 
5.4 
Concomitant Medications ................................................................................................. 50 
5.4.1 Permitted Concomitant Medications..................................................................... 50 
5.4.2 Permitted Concomitant Therapy Requiring Caution ............................................ 50 
5.4.3 Prohibited Medications ......................................................................................... 51 
5.5 
Method of Study Drug Assignment and Randomization .................................................. 51 
5.6 
Blinding/Unblinding ......................................................................................................... 52 
5.7 
Dosing Diary ..................................................................................................................... 52 
5.8 
Study Drug Accountability and Treatment Adherence ..................................................... 52 
5.9 
Continued Access to Study Drug ...................................................................................... 53 
5.10 
External Data Review Committee(s) ................................................................................ 53 
5.10.1 Independent Data Monitoring Committee to Monitor Patient Safety ................... 53 
6 
DESCRIPTION OF STUDY ASSESSMENTS AND PROCEDURES AND 
APPROPRIATENESS OF MEASUREMENTS .............................................................. 54 
6.1 
Informed Consent and Screening ...................................................................................... 54 
6.2 
Demographics and Baseline Disease Characteristics ....................................................... 54 


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6.3 
Medical and Medication History ...................................................................................... 54 
6.4 
Safety Assessments ........................................................................................................... 54 
6.4.1 Physical Examination and Vital Signs .................................................................. 55 
6.4.2 Height and Weight ................................................................................................ 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 ...................................... 57 
6.4.5.3 Blood Volume Summary ....................................................................... 57 
6.5 
Efficacy Assessments ........................................................................................................ 58 
6.5.1 Magnetic Resonance Imaging-Derived Proton Density Fat Fraction ................... 58 
6.5.2 NASH Biomarkers ................................................................................................ 58 
6.5.3 Glycated Hemoglobin (HbA1c) ............................................................................ 58 
6.5.4 Weight ................................................................................................................... 58 
6.6 
Pharmacokinetic Assessments .......................................................................................... 58 
6.7 
Pharmacodynamic Assessments ....................................................................................... 59 
6.8 
Other Assessments ............................................................................................................ 59 
6.8.1 Patient-Reported Outcomes .................................................................................. 59 
6.8.2 FibroScan .............................................................................................................. 59 
6.9 
Appropriateness of the Measures ...................................................................................... 60 
7 
STUDY ACTIVITIES BY STUDY VISIT ...................................................................... 61 
7.1 
Screening (6 weeks; Day -42 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) .......................................................................... 63 
7.3.4 Week 8: Study Day 57 (±2 days) .......................................................................... 64 
7.3.5 Week 10: Study Day 71 (±2 days) ........................................................................ 64 
7.3.6 Week 12: Study Day 85 (±2 days, except MRI-PDFF, ±5 days) ......................... 64 


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7.4 
Early Termination Visit (In-Clinic Visit) ......................................................................... 64 
7.5 
Follow-Up Visit (In-Clinic Visit; 28±5 Days After Last Dose of Study Drug) ............... 65 
7.6 
Telephone Follow-Up Assessment of Survival ................................................................ 65 
7.7 
Unscheduled Visits ........................................................................................................... 65 
8 
SAFETY EVENT DOCUMENTATION AND REPORTING ........................................ 66 
8.1 
Investigator’s Responsibilities .......................................................................................... 66 
8.2 
Monitoring Safety Data During Study .............................................................................. 66 
8.3 
Definition of an Adverse Event ........................................................................................ 66 
8.4 
Definition of a Serious Adverse Event ............................................................................. 67 
8.5 
Suspected Unexpected Serious Adverse Reaction (SUSAR) ........................................... 68 
8.6 
Expectedness ..................................................................................................................... 68 
8.7 
Clinical Significance ......................................................................................................... 68 
8.8 
Clinical Laboratory Adverse Events ................................................................................. 68 
8.9 
Documentation of Adverse Events ................................................................................... 68 
8.10 
Adverse Event Classification ............................................................................................ 69 
8.10.1 Intensity Grades of Adverse Events ...................................................................... 69 
8.10.2 Assessment of Causality: Relationship of Adverse Event to Study Drug or Study 
Procedure .............................................................................................................. 70 
8.11 
Procedures for Reporting a Serious Adverse Event .......................................................... 70 
8.12 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as Adverse 
Events or Serious Adverse Events .................................................................................... 71 
8.13 
Recording Disease Progression......................................................................................... 71 
8.14 
Recording Deaths .............................................................................................................. 71 
8.15 
Adverse Event Follow-Up ................................................................................................ 71 
8.16 
Pregnancy .......................................................................................................................... 71 
8.16.1 Maternal Exposure ................................................................................................ 71 
8.16.2 Paternal Exposure ................................................................................................. 72 
8.17 
Treatment of Overdose ..................................................................................................... 72 
8.18 
Emergency Sponsor Contact ............................................................................................. 72 
9 
STATISTICAL METHODS ............................................................................................. 73 
9.1 
Analysis Populations ......................................................................................................... 73 


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9.2 
Statistical Analyses ........................................................................................................... 73 
9.3 
Hypothesis Testing............................................................................................................ 73 
9.4 
Sample Size ....................................................................................................................... 73 
9.5 
Analysis Plan .................................................................................................................... 74 
9.5.1 Patient Disposition ................................................................................................ 74 
9.5.2 Demographic and Baseline Data ........................................................................... 74 
9.5.3 Prior and Concomitant Medications ..................................................................... 74 
9.5.4 Analysis of the Primary Efficacy Endpoints ......................................................... 74 
9.5.5 Approach to Missing Data Analysis ..................................................................... 75 
9.5.6 Analysis of the Secondary Efficacy Endpoints ..................................................... 75 
9.5.7 Analyses of Exploratory Endpoints ...................................................................... 76 
9.5.8 Safety Analyses ..................................................................................................... 76 
9.5.9 Pharmacokinetic Analysis ..................................................................................... 76 
9.5.10 Pharmacogenetic Analysis .................................................................................... 76 
9.5.11 Interim Analysis .................................................................................................... 76 
10 
ETHICAL AND LEGAL CONSIDERATIONS .............................................................. 77 
10.1 
Compliance with IRB Regulations ................................................................................... 77 
10.2 
Ethical Conduct of the Study ............................................................................................ 77 
10.3 
Protection of Human Patients ........................................................................................... 77 
10.3.1 Compliance with Informed-Consent Regulations ................................................. 77 
10.3.2 Patient Confidentiality .......................................................................................... 78 
10.3.3 Patient Privacy ...................................................................................................... 78 
11 
ADMINISTRATIVE CONSIDERATIONS ..................................................................... 79 
11.1 
Quality Management ......................................................................................................... 79 
11.2 
Study Monitoring .............................................................................................................. 79 
11.3 
Documentation .................................................................................................................. 80 
11.3.1 Source Documentation .......................................................................................... 80 
11.3.2 Case Report Forms ................................................................................................ 80 
11.3.3 Retention of Study Essential Documents .............................................................. 80 
11.4 
Sample Collection, Preparation, and Shipping ................................................................. 80 


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11.5 
Long-Term Retention of Biological Samples ................................................................... 81 
11.6 
Clinical Supplies ............................................................................................................... 81 
11.6.1 Inventory, Reconciliation, Return, and Disposition of Clinical Supplies ............. 81 
11.6.2 Clinical-Supply Inventory ..................................................................................... 81 
11.6.3 Return or Destruction of Study Drug and/or Supplies .......................................... 81 
11.6.3.1 Study Drug Destroyed by the Site ......................................................... 82 
11.6.3.2 Study Drug Returned to Sponsor for Destruction .................................. 82 
11.7 
Drug Accountability.......................................................................................................... 82 
11.8 
Post-trial Care ................................................................................................................... 82 
11.9 
Protocol Noncompliance ................................................................................................... 82 
11.10 Financial Disclosure .......................................................................................................... 83 
11.11 Publication and Disclosure Policy .................................................................................... 83 
12 
REFERENCES ................................................................................................................. 84 
13 
APPENDICES .................................................................................................................. 87 
Appendix A: Schedule of Activities ............................................................................................. 88 
Appendix B: Summary of Changes .............................................................................................. 91 
 


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List of Tables 
 
Table 1 
Study Drug: Description, Packaging, and Storage .................................................44 
Table 2 
Criteria for Dose Modification or Discontinuation Due to Special Safety Events 47 
Table 3 
Permitted Concomitant Medications......................................................................50 
Table 4 
Cautionary Measures for Permitted Concomitant Medications .............................51 
Table 5 
Clinical Laboratory Variables Evaluated During the Study ..................................57 
Table 6 
Pharmacokinetic Parameters to be Evaluated* ......................................................59 
Table 7 
Adverse Event Grades Based on the Common Terminology Criteria for 
Adverse Events ......................................................................................................69 
Table 8 
Causal Attribution Guidance for Adverse Events ..................................................70 
Table 9 
Definitions of Analysis Populations ......................................................................73 
Table 10 
Schedule of Activities ............................................................................................88 
Table 11 
Summary of Changes in Protocol CORT118335-860 Amendment 2 ...................92 
 
List of Figures 
Figure 1 
CORT118335-860 Study Design ...........................................................................33 


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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  
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUDIT 
Alcohol Use Disorders Identification Test 
BCRP 
breast cancer resistance protein 
BMI 
body mass index 
CFR 
Code of Federal Regulations 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DILI 
drug-induced liver injury 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EE 
Efficacy Evaluable 
ELF 
enhanced liver fibrosis 
FSH 
follicle-stimulating hormone 
GC 
glucocorticoid 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
GR 
glucocorticoid receptor 
HbA1c 
glycated hemoglobin  
HCV 
hepatitis C virus 
hERG 
human ether-á-go-go-related gene 
HME 
hot melt extrudate 
HOMA-IR 
Homeostatic model assessment of insulin resistance 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) 


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Abbreviation 
Definition 
IDMC 
Independent Data Monitoring Committee 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IV 
intravenous 
IWRS 
interactive web response system 
Ki 
inhibition constant 
LFC 
liver fat content 
MAD 
multiple-ascending dose 
MMRM 
mixed models for repeated measures 
MR 
mineralocorticoid receptor 
MRI 
magnetic resonance imaging 
MRI-PDFF 
magnetic resonance imaging-proton density fat fraction 
NAFLD 
nonalcoholic fatty liver disease 
NASH 
nonalcoholic steatohepatitis 
NCI 
National Cancer Institute 
NOAEL 
no-observed-adverse-effect level 
PIIINP 
type III procollagen 
PK 
pharmacokinetic(s) 
pro-C3 
propeptide of type III collagen 
QTcF 
QT interval corrected for heart rate using Fridericia’s equation: QTcF=QT/(RR⅓) 
REML 
restricted maximum likelihood 
RSI 
Reference Safety Information 
SAD 
single-ascending dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SDD 
spray-dried dispersion 
SGLT2 
sodium/glucose cotransporter 2 
SoA 
schedule of activities 
TAT 
tyrosine aminotransferase 
TEAE 
treatment-emergent adverse event 
TIMP-1 
tissue inhibitor of metalloproteinases-1 
UGT1A1 
uridine diphosphate glucuronosyltransferase 1A1 
ULN 
upper limit of normal 


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1 
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
1.1 
Therapeutic Area 
Nonalcoholic fatty liver disease (NAFLD) encompasses a range of conditions characterized by 
an increased amount of fat in the liver. In the early stages of NAFLD, the increased deposition of 
fat (steatosis) in the liver is believed to have a benign prognosis. However, NAFLD can develop 
into nonalcoholic steatohepatitis (NASH), which is characterized by histological evidence of 
inflammation, hepatocyte ballooning, and fibrosis. NASH is a progressive liver disorder that can 
lead to cirrhosis, liver failure, and predispose patients to liver cancer (Liu et al. 2016, Machado 
and Diehl 2016, Woods et al. 2015). Though NASH is currently the third most common cause of 
cirrhosis, it is anticipated to become the leading cause of cirrhosis (Konerman et al. 2018). 
Currently, the only current cure for cirrhosis is liver transplantation (Konerman et al. 2018). 
Although the exact pathogenesis of NASH is poorly understood, most patients with NASH 
possess one or more elements of metabolic syndrome (obesity, type 2 diabetes, dyslipidemia) 
(Hazlehurst et al. 2016, Asrih and Jornayvaz 2015). Treatment of NAFLD and NASH is 
primarily focused on lifestyle modification and the management of associated comorbidities. 
Treatments such as vitamin E and pioglitazone have limited efficacy and do not improve fibrosis 
(Sanyal et al. 2010). Although several experimental treatments are under investigation, there is 
currently no approved therapy for treatment of NASH (Konerman et al. 2018). 
1.1.1 Background 
Both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) have been 
implicated in the development and progression of NAFLD, and antagonists of each receptor have 
provided beneficial effects in rodent models of NAFLD and NASH. 
Glucocorticoids (GCs), which are involved in the regulation of energy homeostasis 
(carbohydrate and lipid metabolism), and increased GC levels, have been implicated in the 
pathogenesis of obesity, hyperglycemia, and NAFLD. Elevation of GCs results in increased 
adipose tissue lipolysis, which causes enhanced release of non-esterified fatty acids into the 
circulation. These non-esterified fatty acids are taken up by the liver, leading to increased 
triglyceride synthesis and hepatic steatosis. GCs also increase the de novo synthesis of 
triglycerides by modulation the expression of genes that convert carbohydrates into fatty acids 
(Patel et al. 2014). 
Mineralocorticoids (MCs) are a class of corticosteroids, with the primary MC being aldosterone 
(Gomez-Sanchez E and Gomez-Sanchez CE 2014). The MR, like the GR, is a ligand-activated 
transcription factor and a member of the nuclear receptor superfamily. The MR is unique among 
the steroid receptors in having 2 physiological ligands: aldosterone and cortisol (corticosterone in 
rodents), which bind the receptor with equal affinity (Fuller 2015). Recently, MR was found to 
be widely expressed and has been implicated in pro-inflammatory and pro-fibrotic outcomes in 
multiple organ classes, and in the pathogenesis of diseases such as hypertension and diabetic 
retinopathy (Cole and Young 2017). The full range of genes regulated by MR has not yet been 
elucidated, although several MR-regulated genes have been identified (Fuller 2015). These 
include a number of inflammatory chemokines and cytokines, cyclooxygenase-2 (COX-2), 
osteopontin, transforming growth factor beta (TGF-β), and type III collagens (Lieber et al. 2013). 


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Animal Studies Elucidating the Role of GR and MR in NAFLD and NASH 
Animal studies have contributed to the understanding of the role of GCs in the pathogenesis of 
NAFLD. For example, rodents on a high fat diet and chronically elevated corticosterone had a 
dramatic exacerbation in the development of NAFLD (D’souza et al. 2012). Increased 
intrahepatic lipid synthesis and reduced lipid utilization both contribute to this effect (Wang et al. 
2012). Injection of the synthetic GR agonist dexamethasone in mice increases the expression of 
hepatic diacylglycerol acyltransferase (the enzyme that catalyzes the final step of hepatic 
triacylglycerol synthesis) and decreases the expression of triacylglycerol hydrolase (the lipase 
that hydrolyses intracellular triacylglycerol) leading to increased hepatic triacyl glyceride 
(Dolinsky et al. 2004).  
The role of GR modulation has been demonstrated in several ways. Targeted RNA interference 
of the GR in the livers of diabetic mice resulted in a pronounced decrease in hepatic triglyceride 
concentrations in these mice (Lemke et al. 2008). Administration of the GR antagonist 
mifepristone to mice fed a high fat diet reduced liver injury and resulted in improved insulin 
sensitivity and increased plasma adiponectin concentrations (Hashimoto et al. 2013). 
Aldosterone has also been implicated in NASH. The administration of the MR antagonist 
spironolactone in a mouse model of diet induced diabetes improved hepatic steatosis by 
reducing hepatic inflammation and insulin resistance (Wada et al. 2010). Spironolactone was 
also effective in a rat model of liver fibrosis (Fujisawa et al. 2006). The more selective 
MR antagonist eplerenone also attenuated the progression of liver fibrosis in a rat model of 
NASH (Noguchi et al. 2010), and ameliorated steatosis and hepatic fibrosis in a mouse model of 
NASH (Pizarro et al. 2015). 
Data in Humans Supporting Role of GR and MR in NAFLD and NASH 
Patients with primary aldosteronism, which is caused by excessive production of aldosterone 
by the adrenal gland, have greater insulin resistance and more frequent NAFLD than normal 
controls. NAFLD prevalence has been reported to be 58% in patients with primary 
aldosteronism who are not diabetic or obese, compared with a prevalence of 20% in normal 
controls (Fallo et al. 2010). 
There is also evidence that elevated GCs, either endogenous or exogenous, are associated with 
NAFLD in humans, although the available data are somewhat inconsistent (Papanastasiou et al. 
2017). The GC-driven hepatic steatosis in NAFLD may provide a background for advancement 
to NASH in patients predisposed to lipotoxicity (Marra and Lotersztajn 2013). Additionally, 
GC driven insulin resistance may hasten the advancement of simple steatosis to NASH. Patients 
with NAFLD and diabetes have notably higher prevalence of NASH than patients with NAFLD 
but no diabetes (Friedman et al. 2018).  
1.1.2 Therapeutic Hypothesis 
Miricorilant is a mixed agonist/antagonist of the GR and an antagonist of the MR and is being 
developed for the treatment of NASH. The therapeutic hypothesis is that the combination of 
GR and MR modulation will provide benefit in patients suffering from NASH. The ability of 
miricorilant to prevent weight gain and fat deposition, and reduce lipid accumulation in the 
livers of mice fed a high-fat diet has recently been reported (Mammi et al. 2016). Moreover, 


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Koorneef et al. have reported that miricorilant is able to reverse and prevent high-fat-diet‒
induced lipid accumulation in the liver of mice (Koorneef et al. 2018) by increasing hepatic 
triglyceride secretion.
 
 
 
 
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 presumed NASH. The goal of this study is to evaluate the 
safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of miricorilant in patients 
with presumed NASH based on blood tests and noninvasive imaging measures. 
Detailed information about miricorilant is provided in the current Investigator’s Brochure (IB) 
for miricorilant.  
1.2.1 Nonclinical Summary 
1.2.1.1 
Pharmacology Related to Mode of Action 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2.1.2 
Absorption, Distribution, Metabolism, and Elimination 
 
 
 


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1.2.1.3 
Safety Pharmacology and Toxicology 
 
 
 
 
 
 
  
 
 
 
 
 
 
• 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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 
antipsychotic-induced weight gain (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. 
 


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1.3.2 Phase 1 Study CORT118335-851 
CORT118335-851 was an open-label study conducted with [14C]-miricorilant to assess the 
absolute 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 body 
mass index (BMI) in the range of 18.0 to 30.0 kg/m2. In Part 1, 6 subjects received a single oral 
dose of 900 mg miricorilant in suspension followed by a microdose (100 µg) of 
[14C]-miricorilant containing a microtracer amount of 14C given as an intravenous (IV) infusion. 
In Part 2, 6 subjects received a single oral dose of 150 mg [14C]-miricorilant oral solution in 
 
 
 
 
 
 


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1.3.3 Phase 1 Study CORT118335-852 
CORT118335-852 is a two-part, single-center, double-blind, randomized, placebo-controlled 
assessment of the effect of the miricorilant, 100 mg tablets (as 600 mg [6×100 mg tablets] and 
900 mg [9×100 mg tablets given as a divided dose]) on weight gain induced by multiple doses of 
10 mg olanzapine in healthy male subjects.  
In Part 1, 66 subjects received 10 mg daily of olanzapine for 14 days and were randomized in a 
1:1 ratio to receive 600 mg of miricorilant tablets daily or placebo. Part 1 is complete and final 
unblinded data are available. In Part 2, 30 subjects received 10 mg daily of olanzapine for 
14 days and were randomized in a 4:1 ratio to receive 900 mg of miricorilant tablets daily 
(600 mg in the morning and 300 mg in the evening) or placebo. Part 2 is complete and final 
unblinded data are available. 
 
  
 
 
  
 
 


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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 2a study (CORT118335-860).  
 
  
 
 
 
 
 


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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 reverse recent AIWG caused by olanzapine, risperidone, or quetiapine in obese 
patients (BMI ≥30 kg/m2) with schizophrenia; patients who have been on antipsychotic 
medication for one year or less and have demonstrated weight gain of ≥5% within 6 months of 
starting the medication are eligible. In this multi-center study, approximately 100 patients with 
schizophrenia 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. 
 
 
 
 
  
1.4 
Rationale for Study Design and Dose Regimen  
1.4.1 Design Considerations 
The proposed study examines the safety, efficacy, and PK of miricorilant, a mixed 
agonist/antagonist of the GR and an antagonist of the MR, in patients with presumed NASH 
based on blood tests and noninvasive measures. A role for the GR and MR in NAFLD and 
NASH has been suggested (see Section 1.1), and antagonists of each receptor have shown benefit 
in rodent models of both NAFLD and NASH. 
This Phase 2a proof of concept study is designed to compare 2 doses of miricorilant (600 mg and 
900 mg) to placebo and determine whether once daily dosing of miricorilant for 12 weeks results 
in reduction in liver fat content in patients with presumed NASH. This study will be conducted at 
approximately 15 sites in the US and will randomize approximately 120 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 6 weeks of Screening, 12 weeks of Treatment, and 4 weeks of 
Follow-up. The efficacy of miricorilant versus placebo in reducing liver fat content will be 
assessed. Routine assessments of safety, PK, and tolerability using AE monitoring, measurement 
of vital signs, 12-lead ECG recordings, physical examination, and clinical laboratory safety tests 
will be performed.  
1.4.2 Rationale for Dose Selection and Regimen 
Miricorilant is also being developed for the reversal of antipsychotic weight gain, which is the 
subject of separate investigational new drug application in the US. 
 
 
 
 


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A starting dose regimen of 600 mg once daily has been chosen for this 
study in NASH as it 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 examine the dose/exposure response 
relationship and to help establish an effective and well-tolerated dose in these patients.
 
 
1.5 
Benefits and Risks  
Liver steatosis is thought to precede the development of NASH. Miricorilant has shown efficacy 
in mouse models of NASH, improving steatosis, as well as decrease cellular death and fibrosis. 
Imaging reversal of steatosis by at least 30% is associated with histological improvements of 
NASH on liver biopsy (Patel et al. 2016). Miricorilant is expected to provide benefit in patients 
with presumed NASH by reducing liver fat. 
The risk of clinically significant safety concerns is considered low. However, potential adverse 
effects of miricorilant may include signs and symptoms consistent with excessive GR 
antagonism (e.g., weakness, tiredness, dizziness, orthostatic hypotension, hypoglycemia, 
dehydration, excessive weight loss, nausea, vomiting, diarrhea, and muscle aches), and excessive 
MR antagonism (e.g., hyperkalemia and hypotension).  
Patients will be closely monitored during the study. Standard safety tests such as orthostatic vital 
signs and chemistry panels (refer to Table 5) will be performed at scheduled visits as outlined in 
the Schedule of Assessments (SoA) (Appendix A).  
The effects of 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 5.3.3. 
 


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2 
OBJECTIVES 
The following objectives will be analyzed in patients with presumed NASH: 
2.1 
Primary Efficacy Objective 
• To assess the efficacy of both dose levels of miricorilant versus placebo in reducing 
liver fat content.  
2.2 
Secondary Efficacy Objectives 
• To assess the efficacy of both dose levels of miricorilant combined versus placebo in 
reducing liver fat content. 
• To assess the efficacy of miricorilant versus placebo on change in biomarkers of NASH 
disease activity. 
2.3 
Exploratory Objectives  
• To be assessed by patient group: 
– In all patients, change in adrenocorticotropic hormone (ACTH), serum cortisol, serum 
aldosterone, absolute body weight, and insulin resistance. 
– 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 liver fat 
content. 
• To evaluate the exposure-response relationship between miricorilant and change in liver 
fat content. 
2.4 
Safety Objectives 
• To assess the safety and tolerability of miricorilant versus placebo. 
2.5 
Pharmacokinetic 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 2a, randomized, double-blind, placebo-controlled study conducted in 120 patients 
with presumed NASH, based on blood tests and noninvasive measures, to evaluate the safety, 
tolerability, PK, and preliminary efficacy of miricorilant.  
The study consists of the following study periods: 
• Screening Period: Up to 6 weeks 
• Treatment Period: Day 1 (Baseline) to Week 12 
• Follow-Up Period: 4 weeks after last dose of study drug 
Approximately 120 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 12 weeks of 
treatment (Figure 1). Randomization will be stratified by the presence or absence of diabetes (see 
Section 3.6). See Section 9.4 for details regarding sample size calculation.  
Figure 1 
CORT118335-860 Study Design 
 
Abbreviations: PK, pharmacokinetics; W, week. 
Blood samples for the measurement of miricorilant plasma concentrations will be collected at the 
Week 6 visit according to the PK plan. 
3.2 
Study Endpoints 
3.2.1 Primary Efficacy Endpoint 
Relative change from Baseline to Week 12 in liver fat content assessed by magnetic 
resonance imaging-proton density fat fraction (MRI-PDFF) for both dose levels of 
miricorilant versus placebo. 


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3.2.2 Secondary Efficacy Endpoints 
The following endpoints will be assessed relative to Baseline: 
• Change in liver fat content assessed by MRI-PDFF for both dose levels of miricorilant 
combined versus placebo. 
• Proportion of patients achieving a relative reduction in liver fat content of ≥30% by 
MRI- PDFF for miricorilant versus placebo.  
• Absolute change in liver fat content by MRI-PDFF for miricorilant versus placebo.  
• Change in AST, ALT, and gamma-glutamyl transferase (GGT) for miricorilant 
versus placebo.  
• Change in propeptide of type III collagen (pro-C3) for miricorilant versus placebo.  
• Change in enhanced liver fibrosis (ELF) score and its components (hyaluronic acid, 
tissue inhibitor of metalloproteinases-1 [TIMP-1], type III procollagen [PIIINP]) for 
miricorilant versus placebo.  
3.2.3 Exploratory Endpoints 
The following endpoints will be assessed relative to Baseline: 
• Proportion of patients achieving a relative reduction in liver fat content of ≥50% by 
MRI-PDFF for miricorilant versus placebo. 
• Proportion of patients with complete resolution of fatty liver by MRI-PDFF for 
miricorilant versus placebo.  
In all patients: 
• Changes in ACTH, serum cortisol, and serum aldosterone (pharmacodynamic 
assessments). 
• Change in absolute body weight.  
• Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).  
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 6 for PK variables to be analyzed). 
3.3 
Number of Patients and Study Participation 
3.3.1 Number of Patients 
Approximately 120 patients are planned to enroll in the study (~40 per study arm). 
3.3.2 Duration of Patient Participation 
The maximum expected duration of a patient’s participation is 22 weeks (6 weeks of Screening, 
12 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 12 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 treatment, 
which may be the end of the Treatment Period if the patient completed all treatments or may be 
earlier if the patient discontinued study treatment before the designated stopping point. 
3.4.4 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. 
• 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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3.6 
Diagnosis of Diabetes 
Patients in the study will be stratified by diabetes. Criteria for the diagnosis of diabetes 
(ADA 2018) are as follows: 
1. Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake 
for at least 8 hours. 
2. 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral glucose tolerance test. The 
test should be performed as described by the World Health Organization (WHO 2006), 
using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in 
water. 
3. HbA1c ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a 
method that is National Glycohemoglobin Standardization Program certified and 
standardized to the Diabetes Control and Complications Trial (DCCT) assay. 
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random 
plasma glucose ≥200 mg/dL (11.1 mmol/L).* 
*In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing. 


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4 
STUDY POPULATION 
The following eligibility criteria are designed to select patients with presumed NASH based on 
blood tests and noninvasive measures. 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 ≤75 years old. 
3. Have a diagnosis of presumed NASH with fibrosis defined as meeting all of the 
following criteria: 
a. Either:  
(i) A historical liver biopsy within 1 year of Screening showing NASH, NAFLD 
Activity Score (NAS) ≥4, and F1 to F3 fibrosis  
OR  
(ii) The following two criteria based on non-invasive measurements: 
 AST >17 U/L for women and AST >20 U/L for men AND 
 FibroScan liver stiffness measurement ≥8.5kPa and Controlled Attenuation 
Parameter (CAP) ≥300 dB/m in the 3 months prior to Screening or at 
Screening  
b. MRI-PDFF with ≥10% steatosis 
c. Presence of 2 or more components of metabolic syndrome: type 2 diabetes treatment 
or fasting blood glucose ≥126 mg/dL, BMI ≥30 kg/m2, hypertension treatment or 
blood pressure ≥130/85, history of dyslipidemia, or waist circumference ≥102 cm 
(40 in) in men and ≥88 cm (35 in) in women  
4. Must have consistent ALT and AST Baseline measurements, established by 2 samples 
obtained at least 4 weeks and no more than 6 months apart. At least one of the values 
must be derived from Screening safety labs; historical results within 6 months of 
Screening may be used to provide the second value for eligibility. Unless both samples 
are ≤1.5×the upper limit of normal (ULN), to be eligible for study entry, the difference 
between the first and second measurement of ALT and AST should be ≤50%. A third 
sample may be repeated if the variability between the first 2 values exceeds the 50% 
limit. If the third sample exceeds the 50% limit (compared with the first result), the 
patient is not eligible. 
5. Patients who are taking lipid-modifying therapies must be on stable doses for at least 
3 months prior to Screening and unlikely to change the dose during the study (for patients 
taking statin medications, please see additional restrictions in exclusion criterion #15). 
6. 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 both male patients and female 
patients of childbearing potential; (see Section 4.6.4 and 4.6.5 for details). 


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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 participated in another clinical trial within the last year where patient received 
active treatment for NASH.
2. Have participated in a clinical trial for any other indication within the last 3 months or    
5 half-lives of the treatment, whichever is longer.
3. Have participated in another Corcept study with miricorilant.
4. Women who are pregnant, planning to become pregnant, or are lactating.
5. Have a BMI <18 kg/m2.
6. Are currently using any medications prohibited due to the potential for drug-drug 
interactions (DDI) with study treatments Prohibited medications (see Section 5.4.3) must 
be discontinued at least 5 half-lives prior to a patient receiving their first study treatment. 
Administration of concomitant medications (see Section 5.4) are at the discretion of the 
Investigator and/or the Corcept Medical Monitor.
7. Have had successful weight-loss surgery prior to Screening or are planning weight-loss 
surgery during the study*.
*Patients who have had Roux-en-Y gastric bypass surgery or other surgical procedures 
that have a fundamentally altered gastrointestinal tract may not participate regardless of 
success of the procedure.
8. Have any elective surgery planned during the study.
9. Have significant alcohol consumption, defined as more than 2 drink units per day
(equivalent to 20 g of ethanol) in women and 3 drink units per day (equivalent to 30 g of 
ethanol) in men for ≥3 consecutive months within 1 year prior to Screening, inability to 
reliably quantify alcohol intake, or score a value ≥8 on the Alcohol Use Disorders 
Identification Test (AUDIT) questionnaire.
10. Use of drugs associated with NAFLD (e.g., amiodarone, methotrexate, oral or 
intravenous GCs, at supraphysiological doses (prednisone equivalent ≥5 mg/day), 
tamoxifen, estrogens at doses greater than those used for hormone replacement or 
contraception, anabolic steroids, or valproic acid) for more than 4 weeks in the 2 months 
prior to randomization.
11. Have been treated with obeticholic acid, ursodeoxycholic acid (Ursodiol® and Urso®), 
pioglitazone or high-dose vitamin E (>400 IU/day) within the 3 months prior to 
Screening imaging studies.
12. Have had liver transplantation or plan to have liver transplantation during the study.
13. Have type 1 diabetes.
14. Have type 2 diabetes and:
a.
An HbA1c ≥9.5%
b.
Have had an insulin dose adjustment >10% within 60 days prior to enrollment
c.
Have a requirement for glucagon-like peptide analogue (unless on a stable dose
≥3 months prior to Screening), a requirement for sodium/glucose cotransporter
2 (SGLT2) inhibitors (unless on a stable dose ≥3 months prior to Screening), or 3 or 
more oral anti-diabetic (OAD) agents (unless the OAD is stable and HbA1c <8%)


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d. Have a history of severe hypoglycemia (symptomatic hypoglycemia requiring outside
assistance to regain neurologic status)
15. Are currently taking a statin other than stable doses of the following: lovastatin (up to
20 mg), pravastatin, pitavastatin, simvastatin (up to 10 mg), atorvastatin (up to 20 mg), or
fluvastatin (up to 20 mg). A stable dose is defined as no changes in the dose in the last
3 months prior to Screening.
16. Are currently on the oral antidiabetic drug nateglinide (Starlix).
Patients currently taking the medication may participate in the study if it is 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.
17. Are currently using a medication such as digoxin with an increased risk for toxicity in the
event of electrolyte changes.
18. Have weight loss of greater than 10% within the last 6 months prior to Screening.
19. Have abnormal screening laboratories:
a.
AST >5× upper limit of normal (ULN)
b. ALT >5× ULN
c.
Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2
d. Creatine kinase >3×ULN
20. Have known or suspected cirrhosis based on the opinion of the Investigator. The list
below represents possible signs of suspected cirrhosis:
a.
Physical exam findings:
i. Jaundice
b. Laboratory findings
i. Direct bilirubin >0.3 (except for patients who have Gilbert’s syndrome; see
exclusion criterion #21f)
ii. Platelet count <140,000/µL
c.
Imaging:
i. Evidence of portal hypertension (dilated portal vein, presence of varices)
ii. Evidence of a nodular liver with splenomegaly
d. Endoscopy:
i. Evidence of esophageal varices
21. Have hepatic decompensation defined as the presence of any of the following:
a.
Serum albumin <3.5 g/dL
b. International normalized ratio (INR) >1.3 (unless due to therapeutic anticoagulants)
c.
Total bilirubin >1.3 mg/dL (except for patients who have Gilbert’s syndrome; see
exclusion criterion #21f)
d. History of esophageal or gastric variceal bleedings, ascites, or hepatic encephalopathy
22. Have any other chronic liver disease:
a.
Hepatitis B as defined by presence of hepatitis B surface antigen
b. Hepatitis C as defined by presence of hepatitis C virus (HCV) antibody and positive
HCV RNA. Documented cured HCV infection is acceptable if >3 years from
Screening visit
c.
History of current active autoimmune hepatitis


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d. History or evidence of primary biliary cholangitis
e.
History or evidence of primary sclerosing cholangitis
f.
History or evidence of Gilbert’s syndrome if direct bilirubin is elevated (in addition to
total bilirubin ≥2) or evidence of hemolysis contributing to elevated total bilirubin
g. History or evidence of Wilson’s disease
h. History or evidence of alpha-1-antitrypsin deficiency
i.
History or evidence of hemochromatosis
j.
History or evidence of drug-induced liver disease, as defined on the basis of typical
exposure and history
k. Known bile duct obstruction
l.
Suspected or proven liver cancer
m. Any other type of liver disease other than NASH
23. Have a history of biliary diversion.
24. Are seropositive for human immunodeficiency virus.
25. Have a history of cancer within the last 3 years (in situ carcinomas, cutaneous basal cell
or squamous cell cancer resolved by excision are not excluded).
26. Have contraindications to magnetic resonance imaging (MRI).
27. New York Heart Association class III or IV heart failure, or known left ventricular
ejection fraction <30%.
28. Uncontrolled hypertension (either treated or untreated) defined as systolic blood pressure
˃160 mm Hg or a diastolic blood pressure ˃100 mm Hg at Screening.
29. Uncontrolled cardiac arrhythmia, including confirmed QT interval corrected using
Fridericia’s formula (QTcF) >450 msec for males and >470 msec for females at the
Screening ECG assessment.
30. Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary
artery bypass graft, or stroke within 3 months prior to Screening.
31. Active substance abuse, including inhaled or injected drugs, within 1 year prior
to Screening.
32. Have any clinical condition or significant concurrent disease judged by the Investigator to
complicate the evaluation of the study treatment.
33. Are a family member of one of the Sponsor’s employees, the Investigator, or the
site staff.
34. Are directly working on the study or are a contractor directly involved in the conduct of
the trial.
35. 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.  
Subjects who have an exclusionary laboratory result on initial screening tests may have that 
assessment repeated in consultation with Corcept Medical Monitor, once within the 6-week 
Screening period if the Investigator believes the result was spurious or otherwise confounded. 
The repeat assessment must meet eligibility requirement before the subject proceeds with the 
Screening MRI assessment. 


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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 study treatment while 
remaining on study; that is, the patient may wish to stop treatment early but may agree to 
continue with study visits and/or assessments. 
Early patient “withdrawal” refers either to patient withdrawal of consent to any further study 
participation or to an Investigator/Sponsor decision to permanently withdraw the patient and 
cessation of all study treatments, procedures, and assessments without further follow-up. If a 
patient wishes to withdraw consent to further participation in the study entirely, this should be 
clearly documented (1) in the patient’s medical record and signed by the Investigator and (2) in 
the clinical study database/electronic case report form (eCRF). 
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 study drug, that patient will complete an Early Termination 
(ET) visit at the time of the last dose of the study drug, or soon thereafter. The Follow-Up visit 
will be conducted 28±5 days after the last dose of the study drug. Investigators should encourage 
these patients to continue with all study visits and/or assessments per the patient’s original study 
schedule through Week 12 (end-of-treatment). If the Follow-Up visit coincides with any other 
study visit, the assessments performed at these visits will be combined. If a patient is unable to 
continue with all study visits, they will be encouraged to complete the end-of treatment Week 12 
visit at the very least, in addition to the ET and Follow-Up visits. Patients who complete at least 
6 weeks of treatment and subsequently discontinue will be eligible for evaluation of liver fat 
content by MRI-PDFF. 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 5.3. 
4.4.2 Early Patient Withdrawal from Study 
A patient may be withdrawn early from the study for the following medical or administrative 
reasons: 
•
Withdrawal of consent.


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• Noncompliance, including refusal of the study treatment 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 the Sponsor.  
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 5.4)  
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 
consumption).  
4.6.3 Activity 
Patients should engage in physical activity 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. 
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 


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(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. 
• Women 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.  
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 are not acceptable methods of contraception. 
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.  
4.6.5 Sperm Donation: 
Male patients must agree to not donate sperm during the study and for at least 28 days after the 
last dose of study drug. 
 


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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 
 
 
 
 
 
 
 
 
 
 
 
  
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 11.6. 
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. 


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For the week 6 visit, patients will be instructed to not take their daily study drug prior to the visit, 
but to bring their study drug to the site with them so that the study drug can be administered at 
the site. 
5.2 
Non-Investigational Medicinal Agent  
Not applicable.  
5.3 
Dose Modification 
5.3.1 Dose Reduction 
No dose modification will be allowed. 
5.3.2 Dose Interruption and/or Discontinuation: General Criteria 
Study treatment should be temporarily interrupted if deemed medically necessary by the 
Investigator. On interrupting the study treatment, the Investigator should notify the Corcept 
Medical Monitor. Before restarting study treatment, the Investigator must obtain approval from 
the Corcept Medical Monitor. If the event that necessitated treatment interruption recurs after 
study treatment is restarted, the patient should be permanently discontinued from study 
treatment. In addition, patients will be permanently discontinued from study treatment if they 
experience any of the criteria listed for stopping treatment in Table 2. 
5.3.3 Dose Interruption and/or Discontinuation: Special Safety Events 
Based on the mechanism of action of miricorilant, there is a theoretical risk of excessive 
GR antagonism and excessive MR antagonism. Thus far in clinical experience with miricorilant 
in healthy volunteers as well as in patients with AIWG, an increased incidence of excessive 
GR or MR antagonism has not been observed. 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 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. 
 
 Symptoms should continue to be monitored even after the last dose 
of study medication in the follow-up period; intravenous fluids and hydrocortisone should be 
administered as clinically appropriate to reverse excessive GR and MR antagonism.  
At each study visit starting with the Baseline visit, patients will be evaluated for signs and 
symptoms of excessive GR or MR antagonism. For patients who experience symptoms, the 
actions outlined in Table 2 should be taken. 
Guidelines for temporarily interrupting and restarting and for permanently discontinuing study 
treatment due to other safety events (hyperkalemia; hypotension; excessive miricorilant 


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exposure; suspected liver injury, and significant trauma, surgery, or medical illness) are outlined 
in Table 2. 
For assessment of suspected liver injuries, baseline values for ALT, AST and total bilirubin will 
be the mean of all values obtained from Screening through Day 1. Please refer to the laboratory 
manual or individual subject laboratory report for gender- and age-specific references. 
Elevations of ALT or AST are defined as a baseline ALT or AST <ULN that increased to 
>3×ULN on treatment, or a baseline ALT or AST >ULN and on-treatment >2×baseline. 
Elevations should be confirmed with repeat testing within 48 to 72 hours. If confirmed, and 
if no other cause of laboratory abnormality is immediately apparent, the Corcept Medical 
Monitor is to be notified. Patients with ALT or AST elevations must be placed into close 
observation (see Table 2). 
 


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Table 2 
Criteria for Dose Modification or Discontinuation Due to Special Safety Events 
Safety Event 
Criteria for Interrupting and Restarting Study Treatment and Patient 
Management 
Criteria for Stopping Study Treatment 
Excessive GR or 
MR antagonism 
Criteria: signs and symptoms of excessive GR and MR antagonism (Section 1.5) 
Management:  
• Immediately interrupt miricorilant treatment for ≥5 days and start standard 
supportive care, including 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 an 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 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 supported 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. 
• Restart miricorilant only if hypotension is transient and reversible and not 
related to study medication, and after consultation with the Corcept Medical 
Monitor. 
Systolic BP <100 mm Hg or diastolic BP <60 mm 
Hg (as confirmed by 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 Treatment and Patient 
Management 
Criteria for Stopping Study Treatment 
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: development of suspected liver injury while on study drug 
Management: 
• Repeat liver biochemistries (ALT, AST, 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 as needed, if required in the opinion of the 
Investigator. 
• Obtain additional tests to evaluate liver function, as appropriate (e.g., INR, 
direct bilirubin). 
• Continue to monitor the liver biochemistry at least twice weekly. Frequency can 
decrease to once a week or less if abnormalities stabilize or study drug has been 
discontinued and the patient is asymptomatic. 
• During the period of close observation, study drug can be continued if desired at 
the discretion of Corcept Medical Monitor and Investigator. 
For patients with elevated baseline AST, ALT, 
total/direct bilirubin (>ULN) 
• If baseline value was <2×ULN, discontinue if 
ALT or AST increases to >5×baseline. 
• If baseline value was ≥2×ULN but <5×ULN, 
discontinue if ALT or AST increases to 
>3×baseline.  
• If baseline value was ≥5×ULN, discontinue if 
ALT or AST increases to >2×baseline. 
• If ALT or AST increases to >2×baseline value 
and the increase is accompanied by a 
concomitant increase in total bilirubin to 
>2×baseline value or an increase in INR by >0.2. 
If a patient has Gilbert’s syndrome, ≥35% of total 
bilirubin must also be direct bilirubin. 
• In any patients with signs and symptoms of 
fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or 
eosinophilia (>5%). 


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Safety Event 
Criteria for Interrupting and Restarting Study Treatment and Patient 
Management 
Criteria for Stopping Study Treatment 
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; DILI, drug-induced liver 
injury; ECG, electrocardiogram; GR, glucocorticoid receptor; INR, international normalized ratio; MR, mineralocorticoid receptor; SBP, systolic blood 
pressure; ULN, upper limit of normal. 


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5.3.4 Pharmacokinetic Criteria for Dose Adjustment or Discontinuation 
Not applicable.  
5.4 
Concomitant Medications 
Administration of concomitant medications are at the discretion of the Investigator and/or the 
Corcept Medical Monitor.  
5.4.1 Permitted Concomitant Medications 
Medications required to treat AEs, manage symptoms, concurrent diseases, and supportive care 
agents, such as pain medications, anti-emetics, and antidiarrheal agents, are allowed at the 
discretion of the Investigator and/or the Corcept Medical Monitor. Patients must be instructed to 
notify the investigational site about any new medications they take after the start of the study 
drug. All medications (other than study drugs) administered 28 days before study entry (i.e., after 
a patient signs the ICF) and during the study must be listed on the concomitant medications 
eCRF. 
Permitted concomitant medications are listed in Table 3. 
Table 3 
Permitted Concomitant Medications 
Medication 
Use and/or Restriction 
Insulin and oral antidiabetic 
medication 
Dose can be decreased during treatment with study drug to prevent 
hypoglycemia; upward titration should be avoided and may occur only 
after consultation with the Corcept Medical Monitor. 
Antihypertensive medication 
Dose can be decreased during the 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-modifying drug  
No changes in current dose allowed from 6 weeks before Baseline 
through the Follow-up Visit. 
Do not add new lipid-modifying medications without prior consultation 
with the Corcept Medical Monitor. 
5.4.2 Permitted Concomitant Therapy Requiring Caution 
Permitted concomitant medications to be used with caution from 1 week before Baseline through 
the Follow-up Visit are as follows:  
• Moderate inducers of CYP2C19. 
• Strong inhibitors of CYP3A4, CYP2C8, and/or CYP2C9. 
• Prescription or over-the-counter medications that are a substrate for breast cancer 
resistance protein (BCRP) or uridine diphosphate glucuronosyltransferase 1A1 
(UGT1A1) and are not prohibited with BCRP and/or UGT1A1 inhibitors and for which 
an acceptable dose modification can be implemented to allow coadministration with 
miricorilant.  
• Medications that carry a possible risk for QT prolongation. 
 


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Table 4 
Cautionary Measures for Permitted Concomitant Medications 
Medication 
Cautionary Actions 
Simvastatin  
Simvastatin should be dosed in the evening as per its label and separated 
from the morning dose of miricorilant by 12 hours. 
Atorvastatin 
Atorvastatin should be dosed in the evening and separated from the 
morning dose of miricorilant by 12 hours.  
Fluvastatin 
Fluvastatin should be dosed in the evening as per its label and separated 
from the morning dose of miricorilant by 12 hours. 
Glyburide 
Fingerstick blood glucose monitoring may need to be increased from 
Baseline to Week 2. 
Losartan 
Dosing should be separated from miricorilant by 12 hours.   
Blood pressure monitoring may need to be increased from Baseline to 
Week 2. 
 
The Corcept Medical Monitor should be contacted in the case of any clarifications regarding 
concomitant therapy.  
5.4.3 Prohibited Medications 
The following medications are prohibited during treatment with miricorilant in this study: 
• Other investigational therapies. 
• Prescription or over-the-counter medications that are moderate and strong inhibitors of 
CYP2C19. 
• Prescription or over-the-counter medications that are strong inducers of CYP2C19. 
• Prescription or over-the-counter medications with a narrow therapeutic index that are 
predominantly metabolized by CYP3A4, CYP2C8, and/or CYP2C9. 
• Prescription or over-the-counter medications that are a substrate for BCRP or UGT1A1 
and have clinically significant in vivo drug-drug interactions with BCRP and/or UGT1A1 
inhibitors and for which an acceptable dose modification is not an option. 
• Digoxin or other medications with increased risk for toxicity in the event of electrolyte 
changes. 
• Systemic corticosteroids (with exception of temporary use for treatment of excessive 
GR antagonism), potent (group III) topical corticosteroids, and intra-articular 
corticosteroid. 
• The oral antidiabetic drug nateglinide (Starlix). 
5.5 
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 
diabetes status to ensure that there will be an equal number of patients with diabetes in each 
treatment group. Before the study is initiated, the log-in information and directions for the IWRS 
will be provided to each site. 
Study drug will be dispensed at the study visits summarized in the SoA (Appendix A).  


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Returned study drug should not be re-dispensed to the patients. However, study treatment 
brought back by the patient for accounting reasons can be returned to the patient. 
5.6 
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 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.  
5.7 
Dosing Diary 
A dosing diary will be provided, and patients will be instructed to return all unused study 
drug 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 as well as the date and time 
of study drug administration. Time and dose administered should be documented in the 
clinic charts. 
5.8 
Study Drug Accountability and Treatment Adherence  
Study drug adherence will be determined by review of the patient dose diary and counting 
returned tablets. On visit days, study drug should be taken in the clinic during the visit and after 
initial blood draws. 
A patient who is assigned a study drug (i.e., to 600 mg miricorilant, 900 mg miricorilant or 
placebo, for 12 weeks of treatment) will be considered nonadherent if he or she misses >20% 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 


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should be assessed to determine the reason for nonadherence and educated and/or managed as 
deemed appropriate by the Investigator to improve adherence.  
5.9 
Continued Access to Study Drug 
There is no provision for continued access to study drug. 
5.10 
External Data Review Committee(s) 
5.10.1 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 3 voting 
members: two physicians and one statistician. The IDMC will meet at least quarterly. Further 
details describing the IDMC composition, contents of data reports, responsibilities, and decision 
rules will be described in the IDMC Charter. 
 


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6 
DESCRIPTION OF STUDY ASSESSMENTS AND PROCEDURES AND 
APPROPRIATENESS OF MEASUREMENTS 
Study procedures and their timing are summarized in the SoA (Appendix A). Protocol waivers or 
exemptions are not allowed.  
The Investigator and Sponsor will conduct the study in accordance with International Council 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. The medical history will be updated at the Day 1 Visit and will then 
serve as the baseline for other clinical assessments. 
6.4 
Safety Assessments 
Safety will be determined from evaluation of AEs, physical examinations, clinical laboratory 
tests, vital signs, and ECGs.  


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6.4.1 Physical Examination and Vital Signs  
Comprehensive physical examinations will be performed at Screening, Baseline, Early 
Termination, and Follow-up. Symptom-directed physical examinations will be performed at the 
other study visits. Genitourinary, rectal, and breast examinations are not required. 
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 will include resting heart rate, 
blood pressure, respiratory rate, and body temperature. Systolic and diastolic blood pressure will 
be measured after patients have been at rest (seated) for at ≥3 minutes. Blood pressure will be 
recorded in mm Hg. Heart rate (beats per minute) will be measured 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 and Weight 
Height will be measured once, at Screening. 
Weight will be measured at every visit. Body weight will be measured without overcoat and 
shoes, and with only light clothing. 
BMI will be autocalculated from the electronic data capture (EDC) database at every visit.  
6.4.3 Electrocardiogram 
Twelve-lead ECG tracings will be obtained in triplicate from all patients at each visit during the 
study. 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 of the ICF until 28 days after the last dose of 
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. Additional analyses may be performed to evaluate the effects of miricorilant 
(see Appendix A).  
Laboratory values for an analyte that are outside of the normal range for that analyte per the 
applicable central or local laboratory will be identified and assessed as clinically significant or 
not and can be 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 5 and should be performed according to the 
schedule provided in the SoA (Appendix A). 


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Table 5 
Clinical Laboratory Variables Evaluated During the Study 
Hematology 
Serum Chemistry 
Pharmacodynamic Biomarkers 
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 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  
Serum Creatinine 
Bilirubin (total and direct) 
Albumin  
Alkaline phosphatase 
Aspartate aminotransferase  
Alanine aminotransferase 
Plasma glucose (fasting) 
Serum insulin (fasting)  
Glycated hemoglobin (HbA1c) 
Blood urea nitrogen 
Uric acid  
Bicarbonate  
Total protein  
Gamma-glutamyl transferase 
(GGT) 
Creatine kinase 
Adrenocorticotropic hormone (ACTH) 
Serum cortisol 
Serum aldosterone 
Propeptide of type III collagen 
(pro-C3) 
Enhanced liver fibrosis (ELF) score 
and components (hyaluronic acid, 
tissue inhibitor of 
metalloproteinases-1 [TIMP-1], type 
III procollagen [PIIINP]) 
Other Biomarkers  
Glucocorticoid receptor activity 
Pharmacokinetics 
Miricorilant  
Lipid Panel (Fasting) 
Pregnancy 
Total cholesterol 
Low-density lipoprotein-cholesterol 
High-density lipoprotein-cholesterol 
Very-low-density lipoprotein 
cholesterol 
Triglycerides 
Serum/urine pregnancy test (for 
women of childbearing potential) 
Hormones 
Follicle-stimulating hormone 
(FSH) 
Coagulation 
Other 
 
Prothrombin/international normalized 
ratio 
Partial Thromboplastin time 
Virus screen (human immune-
deficiency virus, hepatitis C 
and B viruses)  
 
Note: See the Schedule of Assessments (Appendix A) for the laboratory test schedule. 
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 11.5. 
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. 


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6.5 
Efficacy Assessments  
All efficacy assessments will be performed at the time points specified in the SoA (Appendix A). 
6.5.1 Magnetic Resonance Imaging-Derived Proton Density Fat Fraction 
Recent data support the use of MRI-PDFF in early-phase NASH clinical trials, as a 
noninvasive, quantitative measure of the level of fat in the liver (Caussy et al. 2018). Changes 
in liver fat content greater than 30% are correlated with improvements in liver fibrosis by biopsy 
(Patel et al. 2016). MRI-PDFF will be performed to determine the degree of LFC reduction. 
Instructions for preparing for and performing the test will be provided in the study manual. 
6.5.2 NASH Biomarkers 
NASH biomarkers include AST, ALT, GGT, pro-C3, ELF score and its components (hyaluronic 
acid, TIMP-1, PIIINP). 
Blood for measuring levels of AST, ALT, and GGT (as part of the chemistry panel) will be 
collected. 
Small fragments of collagen, called propeptides, are released during fibrosis. Pro-C3 is the 
propeptide of type III collagen and detection of pro-C3 is anticipated to reflect the formation of 
new fibrotic tissue in the liver (Vilar-Gomez and Chalasani 2018). Blood samples for measuring 
pro-C3 will be collected (also see Section 6.6). 
The ELF score combines 3 serum biomarkers (hyaluronic acid, TIMP-1, and PIIINP) which have 
been shown to correlate with the degree of liver fibrosis assessed by liver biopsy 
(Vilar-Gomez and Chalasani 2018). Each of these markers is measured by an immunoassay and 
an ELF score is generated, from which a level of fibrosis severity can be determined. Blood 
samples will be collected at the time points specified in the study SoA (Appendix A, see also 
Section 6.6).  
6.5.3 Glycated Hemoglobin (HbA1c) 
Blood samples will be collected from all patients to measure HbA1c, a glycoprotein whose 
concentration reflects the amount of glucose bound to hemoglobin (Bala et al. 2017). Blood 
samples will be collected at the time points specified in the SoA (Appendix A).  
6.5.4 Weight 
Weight will be measured at all visits and will be used in BMI calculations.  
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 6). Pharmacokinetic data may also be 
used in safety and/or efficacy evaluations related to concerns arising during or after the study.  


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Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
Table 6 
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 
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 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, or serum) will be obtained, some for analysis during the 
study and others for future analysis. 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. 
In the event of pharmacodynamic marker extraction failure, a replacement blood sample may be 
requested from the patient. 
6.8 
Other Assessments 
6.8.1 Patient-Reported Outcomes 
An alcohol consumption screen will be performed at Screening. AUDIT is a validated 10-item 
questionnaire developed to assess alcohol consumption, drinking behaviors, and alcohol-related 
problems. A score of 8 or more is considered to indicate hazardous or harmful alcohol use 
(Reinert and Allen 2007).  
6.8.2 FibroScan 
FibroScan is a specialized ultrasound machine that is used to measure both liver fibrosis and 
steatosis (Afdhal 2012). FibroScan will be performed at Screening (or scans performed 3 months 


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within Screening are acceptable). Instructions for preparing for and performing the test will be 
provided in the study manual.  
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 ACTIVITIES BY STUDY VISIT 
An SoA is provided in Appendix A. 
Corcept will be promptly notified of any protocol deviations. 
The acceptable visit window for all visits during the Treatment Period is ±2 days and the 
acceptable visit window for the Follow-Up Period is ±5 days. 
7.1 
Screening (6 weeks; Day -42 to Day -1) 
Screening will occur within 6 weeks before the first dose of the study drug. 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 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 and assessments will be performed: 
• Obtain informed consent 
• Record medical history  
• Record prior and concomitant medications 
• Record AEs 
• Record demographic information 
• Perform physical examination 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Measure height and body weight 
• Measure waist circumference  
• Conduct AUDIT screen 
• Obtain FibroScan or verify that FibroScan has been done within 3 months of Screening 
• Draw blood samples for laboratory tests 
– Chemistry panel 
– Hematology with platelet and WBC count differential 
– Lipid Panel 
– Serum pregnancy test (women of childbearing potential only) 
– FSH for females who have a medically confirmed ovarian failure or are 
postmenopausal 
– Prothrombin time/international normalized ratio (INR) 
– HbA1c 


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– HIV screening  
– Hepatitis B (HBV) screening  
– Hepatitis C (HCV)screening 
• If patient continues to be eligible following laboratory tests, perform MRI-PDFF during a 
separate visit. 
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 history and review of medications 
– Perform urine pregnancy test (women of childbearing potential only); if urine 
pregnancy test is positive, the result should be confirmed with a serum pregnancy test 
– Measure body weight 
– 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 
• Draw blood samples for laboratory tests 
– Chemistry panel 
– Hematology with platelet and WBC count differential 
– Lipid panel 
– Serum cortisol (morning 8:00–AM ±1 hour) 
– Serum aldosterone  
– ACTH (morning 8:00–AM ±1 hour) 
– Prothrombin time/INR  
– HbA1c  
– Serum insulin 
– Plasma glucose 
– NASH biomarkers (Table 5) 
• Other Biomarker Assessment 
– Glucocorticoid-receptor activity marker 
• Record AEs 
• Perform study randomization  
• Dispense study drug; patient will take their first dose of study drug in the clinic at this 
visit after clinic assessments 
• Provide the patient with dose diary  


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7.3 
Treatment Period 
The patient should be instructed to fast (no food or drink other than water) before each clinic 
visit for at least 8 hours.  
At all clinic visits during the Treatment Period, the following will be performed: 
• Record any AEs 
• Record concomitant medications 
• Perform urine pregnancy test (women of child-bearing potential); if urine pregnancy test 
is positive, the result should be confirmed with a serum pregnancy test 
• Perform physical examination 
• Measure body weight 
• Record vital signs (including orthostatic vital signs) 
• Perform 12-lead resting ECG (in triplicate) 
• Perform laboratory tests: 
– Chemistry panel 
– Hematology with platelet and WBC count differential 
• Record unused study drug brought back by the patient 
• Evaluate study treatment adherence 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) 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Dispense study drug  
7.3.2 Week 4: Study Day 29 (±2 days) 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Perform laboratory tests: 
– Lipid panel  
– Serum insulin 
– Plasma glucose  
• Dispense study drug  
7.3.3 Week 6: Study Day 43 (±2 days) 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. For the PK analysis, all patients will be required to take their dose in the clinic 
(witnessed dosing) at the Week 6 visit, following a meal. 
• Dispense study drug  


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• NASH Biomarkers 
• Draw blood samples for PK analysis 
7.3.4 Week 8: Study Day 57 (±2 days) 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Perform laboratory tests: 
– Lipid panel  
– Serum insulin 
– Plasma glucose  
• Dispense study drug  
7.3.5 Week 10: Study Day 71 (±2 days) 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Dispense study drug  
7.3.6 Week 12: Study Day 85 (±2 days, except MRI-PDFF, ±5 days) 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Perform laboratory tests 
– Lipid panel 
– ACTH (morning 8:00–AM ±1 hour) 
– Serum cortisol (morning–8:00 AM ±1 hour) 
– Serum aldosterone  
– HbA1c  
– Plasma insulin 
– Plasma glucose 
• NASH biomarkers (Table 5) 
• Other Biomarker Assessment 
– Glucocorticoid-receptor activity marker 
• Perform MRI-PDFF (Day 85±5 days) 
7.4 
Early Termination Visit (In-Clinic Visit) 
Patients who discontinue the study drug before the end of the Treatment Period (12 weeks) will 
be asked to complete an ET visit at the time of the last dose of study drug (or soon thereafter). 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Perform laboratory tests 
– Lipid panel 


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– ACTH (morning 8:00–AM ±1 hour) 
– Serum cortisol (morning 8:00–AM ±1 hour)  
– Serum aldosterone 
– HbA1c  
– Serum insulin 
– Plasma glucose 
– NASH biomarkers (Table 5) 
• Perform MRI-PDFF (patients with ≥6 weeks of treatment only) 
• Other Biomarker Assessment 
– Glucocorticoid-receptor activity marker 
7.5 
Follow-Up Visit (In-Clinic Visit; 28±5 Days After Last Dose of Study Drug)  
For patients who complete 12 weeks of treatment or for patients who discontinue early from the 
study drug, the Follow-Up visit will be conducted 28±5 days after their last dose of study drug 
The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. 
• Perform laboratory tests: 
– Lipid panel  
– Serum insulin 
– Plasma glucose  
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 Study 
Safety results collected during the study (e.g., AEs, laboratory test 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, a safety assessment committee will monitor the safety findings on a regular basis to 
protect the safety and ethical interests of patients. The details of the safety monitoring will be 
specified in a safety surveillance plan. 
In addition, an IDMC will be established to conduct periodic reviews of data to ensure the safety 
of patients (see Section 5.10). 
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. 


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• Signs, symptoms, or the clinical sequelae of a suspected overdose of either the study drug 
or a concurrent medication. 
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. 


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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 AE, regardless of seriousness, 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. 
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 or 4 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. 


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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.  
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 7 
should be used to evaluate the grade of severity for the AE. 
Table 7 
Adverse Event Grades Based on the Common Terminology Criteria for 
Adverse Events 
Grade 
Description 
1 
Mild: asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated 
2 
Moderate: minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living (e.g., preparing meals, shopping for groceries or clothes, using 
the telephone, and managing money) 
3 
Severe: severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting selfcare activities of daily living (e.g., 
bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden) 
4 
Life-threatening: Life-threatening consequences; urgent intervention indicated 
5 
Death: Death related to AE 
Source: National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 
(NCI 2017). 


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8.10.2 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 8. 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. 
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 assess 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 8 
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 listed on the 
cover page 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 
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SAE reporting details are provided below: 
Covance Pharmacovigilance & Drug Safety Services   
Phone: 1 888-724-4908 
Fax: 1 888-887-8097 
Email: SAEintake@covance.com  
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. 


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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. 
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 5.3.3. 
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 listed on the cover page. 


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9 
STATISTICAL METHODS 
9.1 
Analysis Populations 
The analysis populations are defined in Table 9.  
Table 9 
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) Populationa 
All patients who receive at least 1 dose of study drug. 
Efficacy Evaluable (EE) 
Population 
All patients who receive at least 1 dose of study drug and remain in the trial 
for at least 6 weeks. If a patient in the EE Population does not have at least 
1 post-Baseline efficacy assessment for a particular efficacy endpoint, that 
patient will be excluded from the analysis of that endpoint. 
PK Population 
All patients who have evaluable PK data. 
Abbreviations: ICF, informed consent form; 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. 
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. 
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 relative change in liver fat content from 
Baseline to Week 12. For each test, the null hypothesis is that there is no difference between 
miricorilant and placebo in relative change in liver fat content. 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 
The planned sample size is approximately 40 patients/group or approximately 120 subjects 
randomized 1:1:1 across 2 miricorilant treatment groups and one placebo group. The sample size 
calculation assumes that the SD for change in LFC due to treatment will be comparable to that 
observed in Patel et al. 2016, where an SD of 33% was reported, and in Harrison et al. 2019, 
where the SD was not reported but can be estimated from confidence intervals to be about 28%. 
A slightly more conservative estimate of 35% is assumed for the calculation here. Assuming that 
placebo patients experience a reduction in LFC of 10%, 34 patients per group affords 80% power 
to detect a significant difference at the α=0.05 level between either miricorilant dose group and 
placebo as long as the miricorilant group achieves a 35% or greater reduction in LFC. Assuming 


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that up to 10% of patients may drop out prior to the Week 12 MRI-PDFF assessment, the 
required sample size increases to 38 patients per group or 114 total patients. The sample size has 
been rounded up to 40 patients per group, or 120 total patients, for convenience. The sample size 
estimate has 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. 
Summaries will be presented by treatment group and for all patients combined. 
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 
Each dose of miricorilant will be compared with placebo on the key efficacy endpoint: the 
relative change from Baseline in LFC assessed by MRI-PDFF, where relative change is defined 
as 100 × (LFC at Week 12–LFC at Baseline)/LFC at Baseline. The primary analysis will use a 
nonparametric, rank analysis of covariance (ANCOVA) that incorporates Baseline LFC as a 
covariate; treatment group (2 dose levels of miricorilant and placebo) and diabetes status 
(stratification factor) as factors; and rank relative change in LFC as the response variable. 
P-values for the comparisons of each miricorilant dose group to placebo will be derived from 
linear contrasts. The Hodges-Lehmann method will be used to estimate the median differences 
between groups and their 95% confidence intervals (CIs). P-values from the comparisons will 
not be adjusted for multiplicity.  
The primary analysis population is the EE Population. A sensitivity analysis will be conducted in 
the mITT Population.  
Another sensitivity analysis of the primary endpoints will be performed that requires fewer 
assumptions than the primary analysis. The sensitivity analysis will employ 2 Wilcoxon 
rank-sum tests to compare each of the miricorilant dose groups to placebo; that is, one test 
will compare 600 mg miricorilant to placebo and another will compare 900 mg miricorilant 
to placebo.  


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The relative change in LFC in each treatment group will be summarized by the median and 25th 
and 75th percentiles. 
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 
The secondary efficacy endpoints will be analyzed using the EE Population unless otherwise 
specified. 
A rank ANCOVA similar to the primary analysis will be used to test for evidence of a dose-
response among the 2 miricorilant dose levels. Like the primary analysis, the model will include 
rank Baseline LFC as a covariate, diabetes status as a factor, and rank relative change in LFC as 
the response variable. But in contrast to the primary analysis, the dose-response model will not 
include the placebo group; that is, the treatment factor will include only the 2 dose levels of 
miricorilant. The two miricorilant dose groups will be compared to each other using linear 
contrasts. The Hodges-Lehmann method will be used to estimate the median differences between 
dose levels and their 95% CIs. Significant differences between groups will be taken as evidence 
of a dose-response relationship. Dose-response will also be assessed graphically using boxplots 
of the relative change in MRI-PDFF for each treatment group. 
A set of 3 Cochran-Mantel-Haenszel (CMH) tests – one for each pairwise comparison of 
treatment groups – will be used to evaluate the secondary endpoint of the proportion of patients 
achieving a relative reduction in LFC of ≥30% by Week 12. Each CMH test will be stratified by 
diabetes status. A p-value will be reported for each test along with an estimate of the common 
relative risk of achieving a ≥30% reduction in LFC. Each relative risk estimate will be 
accompanied by a 95% CI. The percentage of patients in each group who achieve a ≥30% 
reduction in LFC will be presented along with a 95% CI. 
The absolute change in LFC from Baseline to Week 12 will be assessed using a parametric 
ANCOVA model with Baseline LFC as a covariate, diabetes status and treatment group as 
factors, and the arithmetic difference between LFC at Week 12 and Baseline as the response 
variable. Linear contrasts from the model will compare each of the 2 dose levels of miricorilant 
to placebo. A similar ANCOVA that excludes the placebo group will be used to assess dose-
response in absolute LFC change. A linear contrast from the model will compare the 2 doses of 
miricorilant to each other. The least squares means and associated confidence intervals derived 
from each model will be reported. 
Other continuous secondary endpoints that are measured more than once during treatment will be 
analyzed using linear mixed models for repeated measures (MMRM). These endpoints include 
the change in AST, ALT, GGT, pro-C3, and ELF score and each of its components (TIMP-1, 
PIIIN, and hyalauronic acid). Restricted maximum likelihood (REML) estimation will be used. 
Each MMRM model will include Baseline LFC as a covariate; diabetes status, treatment, visit, 
and treatment by visit interaction as fixed effects; and patient within treatment group as a random 
effect. Comparisons of each miricorilant group to placebo and to each other will be based on the 
estimates from the model. 


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9.5.7 Analyses of Exploratory Endpoints 
The proportion of subjects achieving a relative reduction in LFC of ≥50%, and the proportion 
with a complete resolution, will be analyzed using CMH tests analogous to those used to 
evaluate the secondary endpoint of the proportion of patients achieving a relative reduction 
of ≥30%.  
Analyses of continuous endpoints, such as the change in ACTH, serum cortisol, and serum 
aldosterone from Baseline to Week 12, will be analyzed using parametric ANCOVA models 
with Baseline LFC as a covariate, diabetes status (stratification factor) and treatment group as 
factors, and the arithmetic difference between the endpoint at Week 12 and Baseline as the 
response variable. Changes in HbA1c and fasting blood glucose within patients with diabetes 
will employ pairwise Wilcoxon rank-sum tests to compare treatment groups. A similar strategy 
will be used to compare groups on the change from Baseline in blood pressure among patients 
with high blood pressure. 
Exploratory analyses will be described in the SAP finalized before database lock. 
9.5.8 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 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, vital sign measurements, and ECG interval results will be 
summarized as changes from Baseline by parameter by treatment and visit using descriptive 
statistics. Categorical laboratory results may also be summarized using shift tables. 
9.5.9 Pharmacokinetic Analysis 
The PK data obtained from the PK analyses, 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. 
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 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). 
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 and/or 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 Investigator 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. 
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. 


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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, and clinic charts; the Investigator’s patient study 
files; results of diagnostic tests, including laboratory tests and ECGs). All source data should be 
attributable, legible, contemporaneous, original, accurate, and completed. Changes to source data 
should be traceable, should not obscure the original entry, and should be explained, if necessary. 
Investigators must retain all original source documents. The Sponsor or its designee will notify 
Investigators in writing when the trial-related records are no longer needed.  
11.3.2 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 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 CRF data entry at the investigator site must obtain Investigator or 
designee’s authorization. 
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.  
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. 
11.4 
Sample Collection, Preparation, and Shipping 
Instructions for collection, preparation, and shipping of all laboratory samples will be provided 
in the study laboratory manual. 


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11.5 
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. 
11.6 
Clinical Supplies 
11.6.1 Inventory, Reconciliation, Return, and Disposition of Clinical Supplies 
All study drug and related materials should be stored, inventoried, reconciled, and destroyed or 
returned according to applicable state and federal regulations and study procedures. Storage of 
study drug is described in Table 1. 
11.6.2 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.  
Unused study drug must be kept in a secure location for accountability and reconciliation by the 
study monitor. 
11.6.3 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. 


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11.6.3.1 
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. 
11.6.3.2 
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. 
11.7 
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. 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. 
11.8 
Post-trial Care 
Not applicable.  
11.9 
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 may be implemented.  
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.  
Corcept 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.  


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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.  
11.10 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.  
11.11 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. 


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12 
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Asrih M, Jornayvaz FR. 2015. Metabolic syndrome and nonalcoholic fatty liver disease: Is 
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APPENDICES


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Appendix A: Schedule of Activities 
Table 10 
Schedule of Activities 
Assessment 
Screening 
Days -42 to 
-1 a 
Baseline  
Day 1 
Treatment Period 
ET b 
Follow-Up 
28±5 days 
after last 
dose of study 
drug 
Week 2 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Day 15 
±2 days 
Day 29 
±2 days 
Day 43 
±2 days 
Day 57 
±2 days 
Day 71 
±2 days 
Day 85 
±2 days 
Informed consent c  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Inclusion/exclusion criteria c 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Medical history and prior 
medications d 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Demographics 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
AUDIT  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Serum pregnancy test e 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Urine pregnancy test e 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FSH test f  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Physical examination g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height h 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Weight h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Waist circumference 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Vital signs (including 
orthostatic vital signs)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead resting ECG (in 
triplicate) i  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FibroScan j  
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
MRI-PDFF k 
X 
- 
- 
- 
- 
- 
- 
X 
X 
- 
Randomization 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 


Protocol CORT118335-860
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Amendment 2  |  07 December 2020 
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Page 89 
Assessment 
Screening 
Days -42 to 
-1 a 
Baseline  
Day 1 
Treatment Period 
ET b 
Follow-Up 
28±5 days 
after last 
dose of study 
drug 
Week 2 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Day 15 
±2 days 
Day 29 
±2 days 
Day 43 
±2 days 
Day 57 
±2 days 
Day 71 
±2 days 
Day 85 
±2 days 
Study drug dispensing 
- 
X 
X 
X 
X 
X 
X 
- 
- 
- 
Study drug adherence 
- 
- 
X 
X 
X 
X 
X 
X 
X 
- 
Dose diary provided 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Dose diary (assessed and 
returned to patient) 
- 
- 
X 
X 
X 
X 
X 
X 
- 
- 
Virus screen (HIV, HCV, 
HBV) 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Hematology with platelet and 
WBC differential l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry, fasting l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma glucose, fasting l 
- 
X 
- 
X 
- 
X 
- 
X 
X 
X 
Serum insulin, fasting l 
- 
X 
- 
X 
- 
X 
- 
X 
X 
X 
HbA1c l 
X 
X 
- 
- 
- 
- 
- 
X 
X 
- 
Lipid panel, fasting l 
 X 
X 
- 
X 
- 
X 
- 
X 
X 
X 
Prothrombin time/INR l 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
ACTH (morning 8:00–AM±1 
hour) l 
- 
X 
- 
- 
- 
- 
- 
X 
X 
- 
Serum cortisol (morning–8:00 
AM±1 hour) l 
- 
X 
- 
- 
- 
- 
- 
X 
X 
- 
Serum aldosterone l 
- 
X 
- 
- 
- 
- 
- 
X 
X 
- 
NASH biomarkers m 
- 
X 
- 
- 
X 
- 
- 
X 
X 
- 
Glucocorticoid-receptor 
activity marker 
- 
X 
- 
- 
- 
- 
- 
X 
X 
- 
PK samples n 
- 
- 
- 
- 
X 
- 
- 
- 
- 
- 
 
Abbreviations: ACTH, adrenocorticotropic hormone; AE, adverse events; AUDIT, Alcohol Use Disorders Identification Test; ECG, electrocardiogram; ET, early termination; 
FSH, follicle-stimulating hormone; HbA1c, glycated hemoglobin; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; INR, international 


Protocol CORT118335-860
Corcept Therapeutics  
Amendment 2  |  07 December 2020 
Confidential 
Page 90 
normalized ratio; MRI-PDFF, magnetic resonance imaging-proton density fat fraction; NASH, nonalcoholic steatohepatitis; PK, pharmacokinetics; WBC, white blood cell 
count. 
 
a. If a patient continues to be eligible following laboratory tests at Screening, MRI-PDFF will be performed during a separate visit. 
b. 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.  
c. Confirm informed consent was obtained and patient meets inclusion/exclusion criteria prior to randomization at Baseline Day 1 Visit. 
d. 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. 
e. Serum and urine pregnancy tests will be completed on all women of childbearing potential. If urine pregnancy test is positive, the result should be confirmed 
with a serum pregnancy test. 
f. FSH will be completed on women who have a 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 
postmenopausal female. 
g. Comprehensive physical examinations will be performed at Screening, Baseline, Early Termination, and Follow-up. Symptom-directed physical examinations 
will be performed at the other study visits. Genitourinary, rectal, and breast examinations are not required.  
h. BMI will be autocalculated from the EDC database based on height and weight measurements. 
i. At Baseline, 12-lead resting ECG (in triplicate) will be performed both before dosing and 2 hr ±15 min after dosing. 
j. Results from FibroScans performed within 3 months of Screening are acceptable. 
k. MRI-PDFF to be performed at Screening and at Week 12 (Day 85 ±5 days). The assessment should also be completed at the ET visit only if the patient had at 
least 6 weeks of treatment.  
l. All clinical laboratory samples will be collected when the patient is fasting (at least 8 hours); ACTH and serum cortisol tests will be completed in the morning–
8 AM ±1 hour).  
m. NASH Biomarkers include AST, ALT, GGT, pro-C3, ELF score and its components (hyaluronic acid, TIMP-1, PIIINP). 
n. Patients will be required to take their dose of study drug on the day of their Week 6 visit in the clinic (witnessed dosing). 
 


Protocol CORT118335-860
Corcept Therapeutics  
Amendment 2  |  07 December 2020 
Confidential 
Page 91 
Appendix B: Summary of Changes 
Significant changes in Amendment 2 of the protocol compared with the Amendment 1 are 
summarized below. Additional details are provided in Table 11; deleted text is shown as a 
strikethrough and new text is shown in bold font. Minor editorial or stylistic changes made for 
consistency or correction of typographical errors are not redlined nor summarized. 
• Added inclusion criterion (#5) to allow enrollment of patients on stable doses of lipid-
modifying therapies for at least 3 months prior to Screening. 
• Updated exclusion criterion (#15) to align with prohibited medications and permitted 
concomitant medications requiring caution.  
• List of permitted concomitant medications requiring caution updated to align with the list 
of prohibited medications. 
• Cautionary measures for a list of permitted concomitant medications were added. 
• Added instructions for orthostatic vital signs measurement.  
• Clarified window for post-dosing ECG assessment at Baseline.  
• Frequency of creatine kinase assessment updated (occurs at all visits when the chemistry 
assessment is performed). 


Protocol CORT118335-860
Corcept Therapeutics  
Amendment 2  |  07 December 2020 
Confidential 
Page 92 
Table 11 
Summary of Changes in Protocol CORT118335-860 Amendment 2  
Section 
Revisions  
Global Changes  
For the version of the protocol, changed “Amendment 1” to “Amendment 2” and changed the 
date from 14 October 2020 to 07 December 2020. 
Synopsis 
Updated text in synopsis to align with changes in the body of the protocol. 
Expanded the list of key exclusion criteria in the synopsis (the following exclusion criteria 
were previously listed in the body of the protocol only). 
• Women who are pregnant, planning to become pregnant, or are lactating. 
• Have a BMI <18 kg/m2. 
• Are currently using any medications prohibited due to the potential for drug-drug 
interactions (DDI) with study treatments Prohibited medications (see Section 5.4.3) 
must be discontinued at least 5 half-lives prior to a patient receiving their first study 
treatment. Administration of concomitant medications (see Section 5.4) are at the 
discretion of the Investigator and/or the Corcept Medical Monitor. 
….. 
• Have abnormal screening laboratories: 
a. AST >5× upper limit of normal (ULN) 
b. ALT >5× ULN  
c. Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 
d. Creatine kinase >3×ULN 
4.1 Inclusion 
Criteria 
Added inclusion criterion. 
 5. Patients who are taking lipid-modifying therapies must be on stable doses for at 
least 3 months prior to Screening and unlikely to change the dose during the study 
(for patients taking statin medications, please see additional restrictions in exclusion 
criterion #15). 
4.2 Exclusion 
Criteria 
Updated exclusion criterion. 
 15. Use any of the following lipid-modifying therapies*:  
a. Fibrates (except stable doses of fenofibrate for at least 3 months prior to Screening), 
niacin, proprotein convertase subtilisin/kexin type-9 inhibitors, and bile acid 
sequestrants.  
b. All statins except stable doses of atorvastatin (up to 20 mg) , rosuvastatin (up to 10 
mg), and pravastatin (up to 20 mg) for at least 6 weeks prior to Screening are allowed. 
*Stable doses for at least 3 months prior to Screening of fish oils (omega-3 fatty acids, 
eicosapentaenoic acid, and docosahexaenoic acid) and ezetimibe are allowed. 
 15. Are currently taking a statin other than stable of the following: lovastatin (up to 
20 mg), pravastatin, pitavastatin, simvastatin (up to 10 mg), atorvastatin (up to 
20 mg), or fluvastatin (up to 20 mg). A stable dose is defined as no changes in the dose 
in the last 3 months prior to Screening. 
Added the following exclusion criterion. 
 17. Are currently using a medication such as digoxin with an increased risk for 
toxicity in the event of electrolyte changes. 
4.4.1 Early 
Patient 
Discontinuation 
of Study Drug 
Deleted bullet. 
 Study drug may be discontinued in the event of any of the following occurrences: 
• Lack of efficacy. 


Protocol CORT118335-860
Corcept Therapeutics  
Amendment 2  |  07 December 2020 
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Page 93 
Section 
Revisions  
5.4.1 Permitted 
Concomitant 
Meds 
Edited text for clarity.  
 All medications (other than study treatments) administered within 28 days before study 
entry (i.e., after a patient signs the ICF) and during the study must be listed on the 
concomitant medications eCRF. 
 
Table 3 Permitted Concomitant Medications, clarified restrictions for lipid-modifying drugs. 
Third row: 
Lipid-
loweringmodifying 
drug 
No increases changes in current dose allowed from 6 weeks 
before Baseline through the Follow-up Visit. 
Do not add new lipid-loweringmodifying medications without 
prior consultation with the Corcept Medical Monitor. 
 
5.4.2 Permitted 
Concomitant 
Therapy 
Requiring 
Caution 
Edited the list of permitted concomitant therapy to align with the list of prohibited 
medications in Section 5.4.3 and based on current information about miricorilant. 
 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, and/or P-glycoprotein. 
• Prescription or over-the-counter medications that are a substrate for breast 
cancer resistance protein (BCRP) or uridine diphosphate glucuronosyltransferase 
1A1 (UGT1A1) and are not prohibited with BCRP and/or UGT1A1 inhibitors 
and for which an acceptable dose modification can be implemented to allow 
coadministration with miricorilant. 
• Medications that carry a possible risk for QT prolongation. 
 
Table 4 Cautionary Measures for Permitted Concomitant Medications, added cautionary 
measures for a list of permitted concomitant medications. 
Medication 
Cautionary Actions 
Simvastatin  
Simvastatin should be dosed in the evening as per its label and 
separated from the morning dose of miricorilant by 12 hours. 
Atorvastatin 
Atorvastatin should be dosed in the evening and separated from the 
morning dose of miricorilant by 12 hours.  
Fluvastatin 
Fluvastatin should be dosed in the evening as per its label and 
separated from the morning dose of miricorilant by 12 hours. 
Glyburide 
Fingerstick blood glucose monitoring may need to be increased from 
Baseline to Week 2. 
Losartan 
Dosing should be separated from miricorilant by 12 hours.   
Blood pressure monitoring may need to be increased from Baseline 
to Week 2. 
 
5.4.3 Prohibited 
Medications 
Edited the list of prohibited medications to align with Section 5.4.2 and based on current 
information about miricorilant. 
 The following medications are prohibited during treatment with miricorilant in this study: 
…. 
• Prescription or over-the-counter medications that are strong inducers or moderate and 
strong inhibitors of CYP2C19. 
• Prescription or over-the-counter medications that are strong inducers of 
CYP2C19. 
…. 


Protocol CORT118335-860
Corcept Therapeutics  
Amendment 2  |  07 December 2020 
Confidential 
Page 94 
Section 
Revisions  
• Prescription or over-the-counter medications that are a substrate for BCRP or UGT1A1 
and have clinically significant in vivo drug-drug interactions with BCRP and/or 
UGT1A1 inhibitors and for which an acceptable dose modification is not an 
option. 
6.4.1 Physical 
Examination 
and Vital Signs 
Added instructions for orthostatic vital signs. 
Paragraph 4: 
 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. 
6.4.5.1 
Laboratory 
Parameters 
Table 5 Clinical Laboratory Variables Evaluated During the Study, edited assessment for 
creatine kinase to clarify that it will be performed at all visits when the chemistry 
assessment is performed. 
 Creatine kinase (Screening only) 
7.2 Baseline 
(Day 1) 
Edited assessments to include window for ECG assessment post dosing. 
 Perform 12-lead resting ECG (in triplicate) before dosing and 2 hr ±15 min after dosing 
7.3.3 Treatment 
Period Week 6: 
Study Day 43 
(±2 days) 
Clarified that for the PK assessment at Week 6 dosing will be performed following a meal. 
 The following procedures and assessments will be performed in addition to those listed in 
Section 7.3. For the PK analysis, all patients will be required to take their dose in the clinic 
(witnessed dosing) at the Week 6 visit, following a meal. 
8.11 Procedures 
for Reporting a 
Serious 
Adverse Event 
Clarified that SAEs should be reported to designated safety contact in addition to the medical 
monitor; included reporting information in the case of SAEs. 
 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 
listed on the cover page 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: 
Covance Pharmacovigilance & Drug Safety Services   
Phone: 1 888-724-4908 
Fax: 1 888-887-8097 
Email: SAEintake@covance.com 
9.5.6 Analysis of 
the Secondary 
Efficacy 
Endpoints 
Corrected the number of miricorilant dose groups. 
Paragraph 2: 
 A rank ANCOVA similar to the primary analysis will be used to test for evidence of a 
dose-response among the 3 2 miricorilant dose levels. Like the primary analysis, the model 
will include rank Baseline LFC as a covariate, diabetes status as a factor, and rank relative 
change in LFC as the response variable. But in contrast to the primary analysis, the dose-
response model will not include the placebo group; that is, the treatment factor will include 
only the 3 2 dose levels of miricorilant. Each The two miricorilant dose groups will be 
compared to each other using linear contrasts. The Hodges-Lehmann method will be used 
to estimate the median differences between dose levels and their 95% CIs 
Appendix A 
Edited HbA1c assessment in Schedule of Activities to clarify that it is not required for the 
patient to be fasting for this assessment. 
 HbA1c, fasting l 
Edited the footnote for ECG assessment to align with Section 7. 
 
i At Baseline, 12-lead resting ECG (in triplicate) will be performed both before dosing and 
2 hr ±15 min after dosing. 


Protocol CORT118335-860
Corcept Therapeutics  
Amendment 2  |  07 December 2020 
Confidential 
Page 95 
Section 
Revisions  
Clarified the footnote for MRI-PDFF assessment.  
 
k MRI-PDFF to be performed at Screening and at Week 12 (Day 85 ±5 days). The 
assessment should also be completed at the early termination ET visit only if the patient 
had at least 6 weeks of treatment. At the Week 12 visit, the assessment can be performed on 
Day 85±5 days. 
 

SAP_001.pdf: 
 Title: A Phase 2a, Randomized, Double-Blind, 
 Placebo-Controlled Study Evaluating the Safety, Efficacy, and 
 Pharmacokinetics of Miricorilant in Patients with Presumed 
 Nonalcoholic Steatohepatitis (NASH) 
 NCT Number:  NCT03823703 
 Date of Original Protocol: 1 July 2020 








  
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Page 4 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACTH 
adrenocorticotropic hormone 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
AUDIT 
Alcohol Use Disorders Identification Test 
BMI 
body mass index 
CI 
confidence interval 
COVID-19 
coronavirus disease of 2019 
CSR 
clinical study report 
CTCAE 
common terminology criteria for adverse events 
DBP 
diastolic blood pressure 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ELF 
enhanced liver fibrosis 
GGT 
gamma-glutamyl transferase 
HbA1c 
glycated hemoglobin  
HOMA-IR 
homeostatic model assessment for insulin resistance 
ICH 
International Council for Harmonisation 
ID 
identifier  
ITT 
intent-to-treat 
IWRS 
interactive web response system 
LFC 
liver fat content 
LLOQ 
lower limit of quantification 
MedDRA 
medical dictionary for regulatory activities 
MRI-PDFF 
magnetic resonance imaging-proton density fat fraction 
NASH 
nonalcoholic steatohepatitis 
PIIINP 
type III procollagen 
PK 
pharmacokinetic 
pro-C3 
propeptide of type III collagen 


  
Miricorilant, Protocol CORT118335-860 
 Statistical Analysis Plan v1.0  |  30 August 2021  
Confidential 
Page 5 
Abbreviation 
Definition 
PT 
preferred term 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SI 
Système International 
SOC 
system organ class 
SDTM 
Study Data Tabulation Model 
TEAE 
treatment-emergent adverse event 
TIMP-1 
tissue inhibitor of metalloproteinases-1 
ULOQ 
upper limit of quantification 
WHO 
World Health Organization 
 


  
Miricorilant, Protocol CORT118335-860 
 Statistical Analysis Plan v1.0  |  30 August 2021  
Confidential 
Page 6 
CONTENTS 
STATISTICAL ANALYSIS PLAN (SAP) .................................................................................... 1 
APPROVAL SHEET ...................................................................................................................... 2 
CRO REVIEW SHEET .................................................................................................................. 3 
LIST OF ABBREVIATIONS ......................................................................................................... 4 
CONTENTS .................................................................................................................................... 6 
List of Tables .................................................................................................................................. 9 
List of Figures ................................................................................................................................. 9 
1 
INTRODUCTION ............................................................................................................ 10 
2 
STUDY OVERVIEW ....................................................................................................... 10 
2.1 
Overall Design .................................................................................................................. 10 
3 
STUDY OBJECTIVES ..................................................................................................... 11 
3.1 
Primary Efficacy Objective ............................................................................................... 11 
3.2 
Secondary Objective ......................................................................................................... 11 
3.3 
Exploratory Objectives ..................................................................................................... 11 
3.4 
Safety Objective ................................................................................................................ 12 
3.5 
Pharmacokinetic Objective ............................................................................................... 12 
4 
STUDY ENDPOINTS ...................................................................................................... 12 
4.1 
Primary Efficacy Endpoint ............................................................................................... 12 
4.2 
Secondary Efficacy Endpoints .......................................................................................... 12 
4.3 
Exploratory Endpoints ...................................................................................................... 12 
4.4 
Safety Endpoints ............................................................................................................... 13 
5 
SAMPLE SIZE CONSIDERATIONS .............................................................................. 13 
6 
ANALYSIS POPULATIONS .......................................................................................... 13 
6.1 
All Enrolled Population .................................................................................................... 13 
6.2 
Safety Population .............................................................................................................. 14 
6.3 
Intent-To-Treat (ITT) Population ..................................................................................... 14 
7 
DEFINITIONS, COMPUTATIONS AND CONVENTIONS ......................................... 14 
7.1 
Definitions......................................................................................................................... 14 


  
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Page 7 
7.2 
Reporting Conventions ..................................................................................................... 14 
7.3 
Conventions for Dates....................................................................................................... 15 
7.4 
Treatment Group Presentation .......................................................................................... 15 
7.5 
Handling of Missing Data ................................................................................................. 15 
7.6 
Analysis Visit Windows ................................................................................................... 16 
8 
TIMING OF ANALYSES ................................................................................................ 16 
8.1 
Interim Analysis ................................................................................................................ 16 
8.2 
Final Analyses and Reporting ........................................................................................... 16 
9 
STATISTICAL METHODS ............................................................................................. 17 
9.1 
General Statistical Consideration ...................................................................................... 17 
9.2 
Patient Disposition ............................................................................................................ 17 
9.3 
Protocol Deviations ........................................................................................................... 17 
9.4 
Demographic and Baseline Characteristics ...................................................................... 17 
9.5 
Medical History ................................................................................................................ 18 
9.6 
Prior and Concomitant Medications and Subsequent Therapies ...................................... 18 
9.7 
Extent of Exposure and Study Drug Compliance ............................................................. 19 
9.8 
Efficacy Analyses ............................................................................................................. 19 
9.8.1 Primary Efficacy Analysis .................................................................................... 19 
9.8.1.1 Sensitivity Analyses ............................................................................... 20 
9.8.2 Secondary Efficacy Analyses ............................................................................... 20 
9.8.2.1 Relative Change from Baseline in Liver Fat Content for Both Dose 
Levels of Miricorilant Combined vs Placebo ........................................ 20 
9.8.2.2 Responders Achieving a  30% Reduction in Liver Fat Content .......... 20 
9.8.2.3 Absolute Change from Baseline in Liver Fat Content ........................... 20 
9.8.2.4 NASH Biomarkers ................................................................................. 21 
9.8.3 Exploratory Analyses ............................................................................................ 21 
9.8.3.1 Responders Achieving a  50% Reduction in Liver Fat Content .......... 21 
9.8.3.2 Proportion of Patients with Complete Resolution ................................. 21 
9.8.3.3 Homeostatic Model Assessment for Insulin Resistance ........................ 22 
9.8.3.4 Adrenocorticotropic Hormone ............................................................... 22 


  
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Page 8 
9.8.3.5 Serum Cortisol ....................................................................................... 22 
9.8.3.6 Serum Aldosterone................................................................................. 22 
9.8.3.7 Other Exploratory Analyses in Patients with Diabetes or High Blood 
Pressure .................................................................................................. 22 
9.9 
Safety Analyses ................................................................................................................. 22 
9.9.1 Adverse Events ..................................................................................................... 22 
9.9.2 Deaths ................................................................................................................... 23 
9.9.3 Clinical Laboratory Tests ...................................................................................... 23 
9.9.4 Vital Signs ............................................................................................................. 24 
9.9.5 Electrocardiograms ............................................................................................... 24 
9.9.6 Physical Examination............................................................................................ 24 
9.9.7 Pregnancy Tests .................................................................................................... 24 
9.10 
Subgroup Analyses ........................................................................................................... 24 
9.11 
COVID-19 Infection ......................................................................................................... 24 
10 
CHANGES FROM PROTOCOL IN STUDY CONDUCT OR STATISTICAL 
ANALYSIS PLAN ........................................................................................................... 25 
11 
REFERENCES ................................................................................................................. 25 
12 
APPENDIX ....................................................................................................................... 27 
12.1 
Imputation of Missing/Partially Missing Dates ................................................................ 27 
 


  
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Page 9 
List of Tables 
Table 1 
Analysis Visit Windows for Assessments .............................................................16 
 
List of Figures 
Figure 1 
CORT118335-860 Study Design ...........................................................................11 
 
 
 


  
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Page 10 
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 
CORT118335-860, amendment 2, dated 07 December 2020: A Phase 2a, Randomized, Double-
Blind, Placebo-Controlled Study Evaluating the Safety, Efficacy, and Pharmacokinetics of 
Miricorilant in Patients with Presumed Nonalcoholic Steatohepatitis (NASH). 
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 2a, randomized, double-blind, placebo-controlled study conducted in 120 patients 
with presumed NASH, based on blood tests and noninvasive measures, to evaluate the safety, 
tolerability, pharmacokinetics (PK), and preliminary efficacy of miricorilant.  
The study consists of the following study periods: 
 Screening Period: up to 6 weeks 
 Treatment Period: Day 1 (Baseline) to Week 12 
 Follow-up Period: 4 weeks after last study dose (Week 16) 
Approximately 120 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 12 weeks of 
treatment. Randomization will be stratified by the presence or absence of diabetes. 
Blood samples for the measurement of miricorilant plasma concentrations will be collected at the 
Week 6 visit according to the schedule of activities. 
 


  
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Page 11 
Figure 1 
CORT118335-860 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 reducing 
liver fat content.  
3.2 
Secondary Objective 
 To assess the efficacy of both dose levels of miricorilant combined versus placebo in 
reducing liver fat content. 
 To assess the efficacy of miricorilant versus placebo on change in biomarkers of NASH 
disease activity. 
3.3 
Exploratory Objectives 
 To be assessed by patient group: 
 In all patients, change in adrenocorticotropic hormone (ACTH), serum cortisol, serum 
aldosterone, absolute body weight, and insulin resistance. 
 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 liver fat 
content. 


  
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 To evaluate the exposure-response relationship between miricorilant and change in liver 
fat content. 
3.4 
Safety Objective 
 To assess the safety and tolerability 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 
Relative change from Baseline to Week 12 in liver fat content assessed by magnetic 
resonance imaging-proton density fat fraction (MRI-PDFF) for both dose levels of 
miricorilant versus placebo. 
4.2 
Secondary Efficacy Endpoints 
The following endpoints will be assessed relative to Baseline: 
 Change in liver fat content assessed by MRI-PDFF for both dose levels of miricorilant 
combined versus placebo. 
 Proportion of patients achieving a relative reduction in liver fat content 
MRI- PDFF for miricorilant versus placebo.  
 Absolute change in liver fat content by MRI-PDFF for miricorilant versus placebo.  
 Change in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and 
gamma-glutamyl transferase (GGT) for miricorilant versus placebo.  
 Change in propeptide of type III collagen (pro-C3) for miricorilant versus placebo.  
 Change in enhanced liver fibrosis (ELF) score and its components (hyaluronic acid, 
tissue inhibitor of metalloproteinases-1 [TIMP-1], type III procollagen [PIIINP]) for 
miricorilant versus placebo.  
4.3 
Exploratory Endpoints 
The following endpoints will be assessed relative to Baseline: 
 Proportion of patients achieving a relative reduction in liver fat content 
50% by 
MRI-PDFF for miricorilant versus placebo. 
 Proportion of patients with complete resolution of fatty liver by MRI-PDFF for 
miricorilant versus placebo.  
In all patients: 
 Changes in ACTH, serum cortisol, and serum aldosterone (pharmacodynamic 
assessments). 


  
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 Change in absolute body weight.  
 Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).  
In patients with diabetes: 
 Change in HbA1c. 
 Change in fasting blood glucose.  
In patients with high blood pressure: 
 Change in blood pressure. 
4.4 
Safety Endpoints 
The following endpoints will be assessed for miricorilant versus placebo: 
 Incidence of treatment-emergent adverse events (TEAEs), adverse events (AEs), and 
Serious TEAEs. 
 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 electrocardiogram (ECG) parameters. 
5 
SAMPLE SIZE CONSIDERATIONS 
The planned sample size is approximately 40 patients/group or approximately 120 subjects 
randomized 1:1:1 across 2 miricorilant treatment groups and one placebo group. The sample size 
calculation assumes that the standard deviation (SD) for change in liver fat content (LFC) due to 
treatment will be comparable to that observed in Patel et al. 2016, where an SD of 33% was 
reported, and in Harrison et al. 2019, where the SD was not reported but can be estimated from 
confidence intervals to be about 28%. A slightly more conservative estimate of 35% is assumed 
for the calculation here. Assuming that placebo patients experience a reduction in LFC of 10%, 
34 patients per group affords 80% power 
between either miricorilant dose group and placebo as long as the miricorilant group achieves a 
35% or greater reduction in LFC. Assuming that up to 10% of patients may drop out prior to the 
Week 12 MRI-PDFF assessment, the required sample size increases to 38 patients per group or 
114 total patients. The sample size has been rounded up to 40 patients per group, or 120 total 
patients, for convenience. The sample size estimate has not been adjusted for multiple 
comparisons. 
6 
ANALYSIS POPULATIONS 
6.1 
All Enrolled Population 
The All Enrolled population comprises all patients who meet study enrollment criteria.  


  
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6.2 
Safety Population 
The Safety population comprises all patients who receive at least 1 dose of study medication. 
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. Efficacy data will be 
summarized based on the ITT population. 
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 
Study day for efficacy will be calculated in reference to the date of first dose of miricorilant or 
placebo (Study Day 1). For assessments conducted on or after the first dose date, study day is 
calculated as (assessment date  first dose date + 1). For assessments conducted before the first 
dose date, study day is calculated as (assessment date  first dose date). There is no study Day 0.  
Treatment-emergent period: The treatment-emergent period is defined as the period of time from 
the date of the first dose of study drug (inclusive) 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, 25th percentile, and 75th percentile 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 Système International (SI) units 
 For by-visit observed data analyses, percentages will be calculated based on the number 
of patients with non-missing data as the denominator unless otherwise specified.  


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For other continuous endpoints, the summary statistics will include mean, standard 
deviation, median, 25th percentile, 75th percentile, and range (minimum and maximum).  
For categorical endpoints, the summary statistics will include frequency counts and 
percentages.  
Medical history and adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA v 23.0. Adverse event severity will be evaluated using 
the National Cancer Institute Common Terminology Criteria for Adverse Events 
(CTCAE v.5.0).  
Prior therapies and concomitant medications will be coded using the World Health 
Organization (WHO) Drug Dictionary and summarized by Anatomical Therapeutic 
Chemical (ATC) therapeutic subgroup and preferred drug names.  
For continuous values (clinical laboratory values) that are not able to be determined due 
to being less than the lower limit of quantification (LLOQ) or higher than the upper limit 
of quantification (ULOQ), the value will be assigned to one unit lower than the LLOQ or 
one unit higher than the ULOQ for any analyses performed.  The original value will be 
displayed in any listings provided. 
7.3 
Conventions for Dates 
Conventions for calculations with dates are as follows: 
Dates will be stored as numeric variables in the SAS analysis files and reported in 
DDMMMYYYY format (i.e., the Date9. date format in SAS).  
Dates recorded in comment fields will not be imputed or reported in any specific format.  
Intervals that are presented in weeks will be transformed from days to weeks by using the 
following conversion formula, and rounding to 1 decimal place:  
o
WEEKS = DAYS / 7
o
MONTHS = DAYS / 30.4375
o
YEARS = DAYS / 365.25
Detailed rules for imputation of missing/partially missing dates for adverse events and 
prior/concomitant medications/procedures 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 adverse events and 
prior/concomitant medications/procedures. Specific rules for handling of missing or partially 


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missing dates for date of birth, adverse events, and prior/concomitant medications/procedures 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 
the date of first dose (Table 1). If multiple visits fall in the analysis visit window, the one closest 
to the target day will be used.  If two visits are equidistant to the target day, then the later visit 
will be used. 
Table 1 
Analysis Visit Windows for Assessments 
Visit Name 
Start Day 
Target Day 
End Day 
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 
Follow-up 
> Study day of last dose of
study drug 
Initial visit after end of 
treatment 
Additional Follow-up 
> Study day of last dose of
study drug 
Second visit after end of 
treatment 
Note: Any unscheduled and early termination visits that occur after the last dose of study drug will be classified 
in the follow-up period. 
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 study has completed, all 
outstanding queries resolved, and the database has been locked.  


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9 
STATISTICAL METHODS 
9.1 
General Statistical Consideration 
Statistical analyses will be reported with tables, figures, and listings, presented in rich text 
format, and using recommended ICH numbering. Output specifications for all tables, figures, and 
listings will be in conformance with guidelines specified by the ICH of the Electronic Common 
Technical Document Specification (Apr 2003).  
All summaries will be presented by assigned treatment group, or actual treatment group where 
applicable. In addition, data will be tabulated for all patients combined. All relevant data 
collected on the electronic case report form (eCRF) will be presented in by-patient data listings, 
to include the site identifier, patient number, and assigned treatment group. 
In general, continuous variables will be summarized by the number of patients with non-missing 
data, mean, SD, median, 25th percentile, 75th percentile, minimum, and maximum values. 
Categorical variables will be summarized by the number and percentage of patients in each 
category. 
9.2 
Patient Disposition 
Screen failure information is collected in an interactive web response system (IWRS), not on the 
eCRF and it is not be incorporated into the Study Data Tabulation Model (SDTM) database. 
Information on participant screening will be presented in terms of the overall number of 
participants screened, number of patients who are screen failures, reasons for screen failures, and 
the number of participants in screening.  
Participant disposition will show the number of patients who have been enrolled, in each analysis 
population, took study drug, discontinued treatment, discontinued from the study, reasons for 
discontinuations, completed 12 weeks of study treatment, completed the study, and completed 
the follow-up study visit. 
Completion of the follow-up study visit is defined as completing the date of visit eCRF for the 
follow-up visit.  
9.3 
Protocol Deviations 
Protocol deviations will be categorized as important or other according to the protocol deviation 
specification document. A by-patient listing of important protocol deviations will be provided for 
the ITT population.   
Patient eligibility including inclusion and exclusion criteria that were not met at randomization 
will be listed for all patients in the ITT population. 
9.4 
Demographic and Baseline Characteristics 
The following demographic characteristics will be presented for the Safety population in listing, 
and summarized by treatment and overall: 


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Age at informed consent (continuous and categorical variable: < 30, 30-50, and > 50 
years) will be summarized 
Sex  
Of childbearing potential (Yes/No) 
Ethnicity 
Race 
Height 
Weight 
Body mass index (BMI) (continuous and categorical variable: obesity class 1 (30-34.9 
kg/m2), obesity class 2 (35-39.9 kg/m2), extreme obesity class 3 (  40 kg/m2)) 
Alcohol Use Disorders Identification Test (AUDIT) score 
BMI will be calculated as: weight (kg) / [height (cm) / 100]2. 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 Safety population. Frequency counts 
and percentages to summarize patients reporting medical history by system organ class and 
preferred term (coded using MedDRA version 23.0 or above) will be presented.   
9.6 
Prior and Concomitant Medications and Subsequent Therapies 
Medications will be coded using the WHO Drug Global B3 version September 2019 or above. 
Medications entered on the eCRF will be mapped to ATC drug class (level 4) and generic drug 
name.  
A prior medication is defined as any medication administered prior to the date of the first dose of 
study drug. A concomitant medication is defined as any medication administered on or after the 
date of the first dose of study drug and up to and including the last dose date. Medications newly 
administered after the last dose date are defined as subsequent therapies. A medication may be 
defined as more than one medication classification (prior, concomitant, or subsequent). The 
imputation rules for missing start and end date of a concomitant medication are described in 
Section 12.1. 
The proportion of patients who received prior, concomitant, and subsequent therapies or 
medications will be summarized separately for the Safety population. For all table summaries, 
the number and percentage of patients receiving any medication will be summarized by 
treatment group and overall. The preferred drug name and the preferred drug name within ATC 
drug class will be summarized separately and displayed by alphabetical order of ATC and 
descending order of incidence for the preferred drug name. 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. 


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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: 
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 Tablets Received: The total dose received for each study drug will be:  
Total Tablets Received = Total tablets dispensed  Total tablets returned. 
Total Tablets Expected: A patient will have an expected number of tablets determined by 
the earliest start date and the latest end date times six tablets taken daily. For patients 
where their tablets received is either zero or missing, an associated expected number of 
tablets is included in the total tablets expected derivation.  Therefore, the total tablets 
expected to be taken is: 
Total Tablets Expected = Duration of Exposure × 6. 
Compliance: Compliance is calculated for each study drug as: 
Compliance = (Total Tablets Received/ Total Tablets Expected) × 100. 
A by-patient listing including the study drug start date, study drug end date, duration, number of 
pills taken, number of pills expected to be taken, and overall compliance will be produced.   
9.8 
Efficacy Analyses 
Due to observations related to safety, the study was terminated by the sponsor prior to 
completion. The sample size at the time of study termination does not support formal 
comparisons of the treatment groups, and therefore, no efficacy analyses specified in the protocol 
will be performed. Descriptive statistics for efficacy endpoints will be provided as described 
below. 
Furthermore, no patient reached their Week 12 visit, and therefore, descriptive statistics at Week 
12 will not be presented. Instead, descriptive statistics will be provided for all analysis visits up 
to the last non-missing visit.  
9.8.1 
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 in reducing liver fat 
content. More specifically, each dose of miricorilant will be compared with placebo on the 


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relative change from baseline in LFC assessed by MRI-PDFF, where for the lth patient, the 
relative change is calculated as 
where 
 is the LFC measured at visit x for the lth patient, and 
 is the baseline LFC for 
the lth patient. 
Descriptive statistics (mean, standard deviation, median, 25th and 75th percentiles, minimum, and 
maximum) will summarize the relative change from baseline to post-baseline in LFC by 
treatment group and overall. 
9.8.1.1 
Sensitivity Analyses 
No sensitivity analyses will be performed. 
9.8.2 
Secondary Efficacy Analyses 
9.8.2.1 
Relative Change from Baseline in Liver Fat Content 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 descriptive statistics will summarize the relative change from baseline to 
post-baseline in LFC by treatment group.  
9.8.2.2 
Responders Achieving a  30% Reduction in Liver Fat Content  
The second secondary efficacy endpoint is the percentage of patients achieving a  30% 
reduction in the relative change in LFC from Baseline for each of the 2 miricorilant doses versus 
placebo. The endpoint requires calculation of the relative change in LFC as described in Section 
9.8.1.  
The outcome variable will be a binary variable indicating a patient as a responder, that is whether 
the lth patient achieved a  30% reduction in LFC from baseline: 
. 
where 
 is the relative change in LFC (Section 9.8.1). 
A frequency table for the number of patients who have achieved a  30% reduction in LFC from 
baseline to post-baseline will be provided. 
9.8.2.3 
Absolute Change from Baseline in Liver Fat Content 
Descriptive statistics will summarize the absolute (arithmetic) change from baseline in LFC by 
treatment group and overall post-baseline.  


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9.8.2.4 
NASH Biomarkers 
9.8.2.4.1 AST, ALT, and GGT 
Separate from laboratory summaries, descriptive statistics will summarize AST, ALT, and GGT 
by treatment and overall at all non-missing corresponding visits associated with NASH 
Biomarker data collection. The change from baseline in AST, ALT, and GGT will be presented 
by treatment and overall at all non-missing post-baseline analysis visits. 
9.8.2.4.2 Propeptide of Type III Collagen (pro-C3) 
Small fragments of collagen, called propeptides, are released during fibrosis. Pro-C3 is the 
propeptide of type III collagen and detection of pro-C3 is anticipated to reflect the formation of 
new fibrotic tissue in the liver (Vilar-Gomez and Chalasani 2018). 
Descriptive statistics will summarize pro-C3 by treatment and overall at all non-missing visits 
and the change from baseline in pro-C3 by treatment and overall at all non-missing post-baseline 
analysis visits. 
9.8.2.4.3 Enhanced Liver Fibrosis (ELF) Score and Its Components 
The ELF score combines 3 serum biomarkers (hyaluronic acid, TIMP-1, and PIIINP) which have 
been shown to correlate with the degree of liver fibrosis assessed by liver biopsy (Vilar-Gomez 
and Chalasani 2018). Each of these markers is measured by an immunoassay and an ELF score is 
generated, from which a level of fibrosis severity can be determined.  
Descriptive statistics will summarize the ELF score and its components by treatment and overall 
at all non-missing visits and the change from baseline in the ELF score and its components by 
treatment and overall at all non-missing post-baseline analysis visits.  
9.8.3 
Exploratory Analyses 
9.8.3.1 
Responders Achieving a  50% Reduction in Liver Fat Content 
The percentage of patients achieving a  50% reduction in the relative change in LFC from 
baseline for each of the 2 miricorilant doses versus placebo will be determined as described in 
Section 9.8.2.2. A frequency table for the number of patients who have achieved a  50% 
reduction in LFC from baseline to post-baseline will be provided.  
9.8.3.2 
Proportion of Patients with Complete Resolution 
Complete resolution of fatty liver is any MRI-PDFF value less than 5%. A frequency table for 
the number of patients who have achieved complete resolution in LFC from baseline to post-
baseline will be provided. Patients with complete resolution of fatty liver by MRI-PDFF will be 
listed including duration on study drug, last dose date, MRI date, and duration between last dose 
date and MRI date. 


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9.8.3.3 
Homeostatic Model Assessment for Insulin Resistance 
HOMA-IR will be calculated by the central laboratory for each patient at each visit using the 
approximate formula (Matthews et al. 1985):  
HOMA-IR = (glucose (mg/dL) × insulin (µU/mL))/405. 
Descriptive statistics will summarize HOMA-IR by treatment group and overall for all visits and 
the change and percent change from baseline in HOMA-IR by treatment group and overall for all 
post-baseline analysis visit.  
9.8.3.4 
Adrenocorticotropic Hormone 
ACTH will be listed by patient and visit including change from baseline. 
9.8.3.5 
Serum Cortisol 
Like ACTH, serum cortisol will be listed by patient and visit including change from baseline. 
9.8.3.6 
Serum Aldosterone 
Serum aldosterone will be summarized by descriptive statistics including change from baseline 
for all analysis visits during the treatment and follow-up period.  
9.8.3.7 
Other Exploratory Analyses in Patients with Diabetes or High Blood Pressure 
No analyses will be performed for patients with diabetes or high blood pressure. 
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. No comparisons between treatment groups for safety measures 
will be made. 
9.9.1 
Adverse Events 
TEAEs are defined as those AEs with onset on or after the first dose date of study drug or 
existing events that worsened after the first dose during the study and up to and including 28 
days after the last dose of study drug, per protocol. Any AEs reported more than 28 days after the 
last dose of study drug will be considered post-treatment AEs. 
Events reported with a partial onset date (e.g., month and year are reported but the day is 
missing) will be considered to be treatment-emergent, as appropriate, if it cannot be confirmed 
that the event onset was prior to the first dose of study drug based on the available date entries. 
Summaries that are displayed by system organ class (SOC) and preferred terms (PT) will be 
ordered by alphabetical orderof SOC and by descending total incidence PT nested within each 
system organ class. Summaries displayed by PT only will be ordered by descending total 
incidence of PT.  


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Tabular summaries with numbers and percentages of patients that have the following adverse 
events will be provided: 
Overview of TEAEs  
Summary of TEAEs  
Summary of TEAEs related to study drug (defined as possibly related, probably related, 
or related) 
Summary of TEAEs leading to discontinuation 
Summary of Serious TEAEs 
Summary of Serious TEAEs related to study drug 
Summary of Serious TEAEs leading to discontinuation 
Summary of TEAEs with fatal outcome 
Summary of TEAEs with Grade 3 or higher  
All above summaries will be presented by PT, and by PT nested within SOC.  Also, summaries 
by maximum severity will be provided for TEAEs and Serious TEAEs. 
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. Serious 
TEAEs and TEAEs leading to discontinuation will also be listed separately. 
9.9.2 
Deaths 
All deaths during the study, including the Follow-up period, will be listed including the primary 
cause of death.  
9.9.3 
Clinical Laboratory Tests 
All descriptive summaries of laboratory results will be based on data analyzed by the central 
laboratory and presented in SI units. 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  
analysis visit up to and including the Follow-up visit as well as the last post-baseline value. 
Descriptive statistics will be presented for observed values as well as change from baseline for 
all 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 worst post-baseline category will be provided. 
The CTCAE grading will be performed for all available laboratory parameters. The grading used 
for analysis will be based on the laboratory data only, without checking other data points that 
may be referenced in the CTCAE grading. 


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An evaluation of drug-induced serious hepatotoxicity (eDISH) plot will be generated.  
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 ALT (>3xULN, >5xULN, >10xULN, 
and >20xULN), AST (>3xULN, >5xULN, >10xULN, and >20xULN), total bilirubin (>ULN and 
>2xULN), ALP (>1.5xULN), and ALT or AST >3xULN and total bilirubin (>1.5xULN and
>2xULN).  A listing of all patients with liver test abnormalities will be provided including all
laboratory values and corresponding abnormality.
9.9.4 
Vital Signs 
Vital sign parameter measurements, including systolic blood pressure (SBP) and diastolic blood 
pressure (DBP), heart rate, respiratory rate, and body temperature, will be summarized by 
position (seated, supine, and standing). Descriptive statistics will be presented for results, as well 
as change from baseline for all post-baseline analysis visits up to and including the Follow-up 
visit for the Treatment and Follow-up periods. 
Vital signs, including SBP, DBP, heart rate, respiratory rate and body temperature will be listed. 
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 analysis visits 
up to and including the Follow-up visit for the Treatment and Follow-up periods using the 
average of the triplicate readings per patient per visit. 
Twelve-
, 
 not clinically significant , 
 A listing of ECG results will be provided 
including visit, date, and interpretation results. 
9.9.6 
Physical Examination 
Results of the physical examination will be presented in patient data listings by study visit and 
body system. A listing of abnormal physical exam findings by visit and body system will be 
provided. The description of the abnormal finding and indication if the finding was clinically 
significant or not will be displayed. 
9.9.7 
Pregnancy Tests 
Results of the pregnancy tests will be presented in patient data listings by study visit. 
9.10 
Subgroup Analyses 
No subgroup analyses will be performed. 
9.11 
COVID-19 Infection  
Information regarding visits that are affected by coronavirus disease of 2019 (COVID-19) 
pandemic are being collected on the eCRF. A listing of visits that are affected by COVID-19 


  
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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 the 
COVID-19 pandemic will be performed as deemed necessary.  
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. Changes from the protocol statistical analysis include: 
 Removal of the Modified Intent-to-Treat, Efficacy Evaluable, and PK populations. 
 Removal of PK analysis including calculation of the PK parameters of miricorilant 
estimated by noncompartmental methods, summary of PK parameters, and plots of 
plasma concentrations of miricorilant. A PK analysis plan will not be prepared. Any 
reported PK data will be listed as observed. 
 Removal of analyses of exploratory endpoints in patients with diabetes or high blood 
pressure. 
 The sample size at the time of study termination does not support formal comparisons of 
the treatment groups, and therefore, no efficacy analyses specified in the protocol will be 
performed. 
11 
REFERENCES 
E9 Statistical Principles for Clinical Trials, provided by the International Conference on 
Harmonization. Available from: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/e9-statistical-principles-clinical-trials 
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12 
APPENDIX 
12.1 
Imputation of Missing/Partially Missing Dates  
For adverse events 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 adverse events. 
If start date of an adverse event 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. 
ent 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. 
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 adverse event 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. 




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