A Study to Evaluate the Safety, Tolerability & Efficacy o... | NCT02784444

Name	Class
Chiltern International Inc.	INDUSTRY

Label	Type	Description	Intervention Names
MSDC-0602K Dose 1 capsules	Active Comparator	MSDC-0602K Dose 1 capsule taken once daily for 360 days	Drug: MSDC-0602K
MSDC-0602K Dose 2 capsules	Active Comparator	MSDC-0602K Dose 2 capsules taken once daily for 360 days	Drug: MSDC-0602K
MSDC-0602K Dose 3 capsules	Active Comparator	MSDC-0602K Dose 3 capsules taken once daily for 360 days	Drug: MSDC-0602K
Placebo capsules	Placebo Comparator	Matching Placebo capsule taken once daily for 360 days	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
MSDC-0602K	Drug	MSDC-0602K capsules	MSDC-0602K Dose 1 capsules MSDC-0602K Dose 2 capsules MSDC-0602K Dose 3 capsules

Measure	Description	Time Frame
Number of Participants With Hepatic Histological Improvement in NAS	A decrease of at least 2 points in NAS at 12 months. At least a 1 point reduction in either ballooning or inflammation from baseline to 12 months. no increase in CRN fibrosis score (i.e., an increase of 1 stage or more) from baseline to 12 months.	12 months (360 days)

Measure	Description	Time Frame
Number of Subjects With Resolution of NASH With no Worsening of Fibrosis at 12 Months.	CRN ballooning score of 0 at 12-months CRN inflammation score of 0 or 1 at 12-months No increase in CRN fibrosis score from baseline to 12-months	12 months (360 days)
Number of Subjects With Improvement of Fibrosis (CRN Staging Score) by at Least 1 Stage With no Worsening of NASH at 12 Months.

Eligibility Module

Eligibility Criteria

Selected Inclusion Criteria:

Adult subjects 18 years of age or greater
Histological evidence of NASH, based on biopsy, with a NAS (NASH CRN scoring) ≥ 4 with a score of at least 1 in each component of NAS.
Histological evidence of liver fibrosis defined as NASH CRN System fibrosis score F1 to F3.
Subjects with type 2 diabetes mellitus (DM) must be under stable and reasonable control.
Male and female subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) for a period of at least 3 months prior to randomization.
Females should be either postmenopausal (at least 12 months since last menses) or surgically sterilized (bilateral tubal ligation or hysterectomy). Males with female partners of child-bearing potential must agree to use adequate contraceptive methods (including a condom, plus one other form of contraception) if engaging in sexual intercourse.
Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study.

Selected Exclusion Criteria:

Known history of HIV.
Prior liver transplantation.
Other well-documented causes of active chronic liver disease.
History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
History of alcohol abuse or drug abuse within 6 months of Screening.
Type 1 diabetes mellitus.
Current or history of recent (≤ 6 months) use of ursodeoxycholic acid.
Use of concomitant medications with a known significant metabolism by CYP2C8 or CPY2C9.
History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within 6 months prior to randomization.
History of heart failure (including CHF) or previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to randomization.
Blood pressure greater than 160/100 mmHg.
Participation in an investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
Malignancy, including leukemia and lymphoma (excluding basal cell and squamous skin cell cancers and localized prostrate cancer) treated within the last 2 years.

Name	Affiliation	Role
Howard Dittrich, MD	Cirius Therapeutics, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Chandler	Arizona	85224	United States

PubMed Identifier	Type	Citation	Retractions
31697972	Derived	Harrison SA, Alkhouri N, Davison BA, Sanyal A, Edwards C, Colca JR, Lee BH, Loomba R, Cusi K, Kolterman O, Cotter G, Dittrich HC. Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study. J Hepatol. 2020 Apr;72(4):613-626. doi: 10.1016/j.jhep.2019.10.023. Epub 2019 Nov 4.

ID	Title	Description
FG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
FG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 31, 2017	Aug 7, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Hepatic Histological Improvement in NAS

A decrease of at least 2 points in NAS at 12 months.
At least a 1 point reduction in either ballooning or inflammation from baseline to 12 months.
no increase in CRN fibrosis score (i.e., an increase of 1 stage or more) from baseline to 12 months.

Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Number

Participants

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Units	Counts
Participants	OG00074 OG00184 OG00282 OG003

Title

Denominators

Categories

Title	Measurements
	OG00022 OG00125 OG00227 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference in response rates between the MSDC-0602K dose and placebo.	Regression, Logistic	Models are adjusted for presence of diabetes mellitus, baseline fibrosis F1 versus F2/F3, and baseline NAS (0-8).	0.747	Statistical testing was two-sided using a significance (alpha) level of 0.05. No adjustment for multiple comparisons.	Odds Ratio (OR)	0.89			2-Sided	95	0.44	1.81					Superiority

Secondary

Number of Subjects With Resolution of NASH With no Worsening of Fibrosis at 12 Months.

CRN ballooning score of 0 at 12-months
CRN inflammation score of 0 or 1 at 12-months
No increase in CRN fibrosis score from baseline to 12-months

Analysis Population Description: Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Number

Participants

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Secondary

Number of Subjects With Improvement of Fibrosis (CRN Staging Score) by at Least 1 Stage With no Worsening of NASH at 12 Months.

Decrease in fibrosis CRN staging score of >= 1 full stage from baseline to 12 months
No increase in ballooning CRN score from baseline to 12 months
No increase in inflammation CRN score from baseline to 12-months

Analysis Population Description: Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Number

Participants

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg

Secondary

Mean Change From Baseline in NAFLD Activity Score (NAS)

NAS is the sum of the scores of steatosis, inflammation, and ballooning. It has a range of 0 to 8 with higher scores indicating worse disease severity.

Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Mean

Standard Deviation

Scores on a scale

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Secondary

Mean Change From Baseline in CRN Steatosis Score

Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis.

Analysis Population Description: Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Mean

Standard Deviation

Scores on a scale

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Secondary

Mean Change From Baseline in CRN Inflammation Score

Inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe inflammation.

Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation

Posted

Mean

Standard Deviation

Scores on a scale

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Secondary

Mean Change From Baseline in CRN Ballooning Score

Hepatocellular ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe hepatocellular ballooning.

Analysis Population Description: Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Mean

Standard Deviation

Scores on a scale

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Secondary

Mean Change From Baseline in CRN Fibrosis Staging Score

Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis.

Analysis Population Description: Subjects in the Modified Intent-to-Treat Set with available baseline biopsy and 12-month biopsy taken within 14 days of study drug discontinuation.

Posted

Mean

Standard Deviation

Scores on a scale

12 months (360 days)

ID	Title	Description
OG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
OG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
OG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Diverticultis	Infections and infestations	Non-systematic Assessment	EG0001 affected94 at risk EG0011 affected99 at risk EG0020 affected98 at risk EG0031 affected101 at risk
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0022 affected98 at risk EG003
Urinary tract infections	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0011 affected99 at risk EG0020 affected98 at risk EG003
Arthritis bacterial	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Clostridium difficile infection	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0011 affected99 at risk EG0020 affected98 at risk EG003
Device related infection	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Gastroenteritis	Infections and infestations	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Pneumonia bacterial	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0011 affected99 at risk EG0020 affected98 at risk EG003
Cytomegalovirus viraemia	Infections and infestations	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0011 affected99 at risk EG0020 affected98 at risk EG003
Non-cardiac chest pain	General disorders	Non-systematic Assessment	EG0002 affected94 at risk EG0011 affected99 at risk EG0021 affected98 at risk EG003
Chest pain	General disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Drug withdrawal syndrome	General disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Arrhythmia	Cardiac disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Cardiac failure congestive	Cardiac disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Myocardial infarction	Cardiac disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Tachycardia	Cardiac disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Ventricular extrasystoles	Cardiac disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Spondylolisthesis	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Anaemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Splenic haemorrhage	Blood and lymphatic system disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Brain stem ischaemia	Nervous system disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Cerebral ischaemia	Nervous system disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Paraesthesia	Nervous system disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Seizure	Nervous system disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Syncope	Nervous system disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Transient ischaemic attack	Nervous system disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Arteriosclerosis	Vascular disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Hypertension	Vascular disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Hypertensive emergency	Vascular disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Hypotension	Vascular disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Malignant hypertension	Vascular disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Small intestine adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Suicidal ideation	Psychiatric disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Renal failure	Renal and urinary disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Urethral stenosis	Renal and urinary disorders	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0010 affected99 at risk EG0021 affected98 at risk EG003
Transurethral prostatetectomy	Surgical and medical procedures	Non-systematic Assessment	EG0000 affected94 at risk EG0010 affected99 at risk EG0020 affected98 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Urinary tract infection	Infections and infestations	Non-systematic Assessment	EG0004 affected94 at risk EG00110 affected99 at risk EG0023 affected98 at risk EG0035 affected101 at risk
Sinusitis	Infections and infestations	Non-systematic Assessment	EG0005 affected94 at risk EG0016 affected99 at risk EG0025 affected98 at risk EG003
Influenza	Infections and infestations	Non-systematic Assessment	EG0000 affected94 at risk EG0015 affected99 at risk EG0025 affected98 at risk EG003
Upper respiratory tract infection	Infections and infestations	Non-systematic Assessment	EG0007 affected94 at risk EG0016 affected99 at risk EG0023 affected98 at risk EG003
Bronchitis	Infections and infestations	Non-systematic Assessment	EG0003 affected94 at risk EG0012 affected99 at risk EG0026 affected98 at risk EG003
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0007 affected94 at risk EG0018 affected99 at risk EG0027 affected98 at risk EG003
Dirrhoea	Gastrointestinal disorders	Non-systematic Assessment	EG0005 affected94 at risk EG0017 affected99 at risk EG0029 affected98 at risk EG003
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0005 affected94 at risk EG0017 affected99 at risk EG0025 affected98 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	Non-systematic Assessment	EG0004 affected94 at risk EG0014 affected99 at risk EG0025 affected98 at risk EG003
Abdominal pain	Gastrointestinal disorders	Non-systematic Assessment	EG0005 affected94 at risk EG0014 affected99 at risk EG0022 affected98 at risk EG003
Abdominal distension	Gastrointestinal disorders	Non-systematic Assessment	EG0005 affected94 at risk EG0011 affected99 at risk EG0021 affected98 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0005 affected94 at risk EG0014 affected99 at risk EG0023 affected98 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0003 affected94 at risk EG0013 affected99 at risk EG0025 affected98 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0008 affected94 at risk EG0015 affected99 at risk EG0022 affected98 at risk EG003
Oedema peripheral	General disorders	Systematic Assessment	EG0006 affected94 at risk EG0015 affected99 at risk EG0029 affected98 at risk EG003
Headache	Nervous system disorders	Non-systematic Assessment	EG0002 affected94 at risk EG0014 affected99 at risk EG0025 affected98 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0003 affected94 at risk EG0015 affected99 at risk EG0021 affected98 at risk EG003
Rash	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0001 affected94 at risk EG0015 affected99 at risk EG0021 affected98 at risk EG003

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Title	Description
BG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules
BG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
BG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
BG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Matching Placebo capsule taken once daily for 360 days Placebo: Placebo capsules	1	94	9	94	75	94
EG001	MSDC-0602K 62.5 mg	MSDC-0602K 62.5 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules	0	99	5	99	78	99
EG002	MSDC-0602K 125 mg	MSDC-0602K 125 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules	1	98	13	98	76	98
EG003	MSDC-0602K 250 mg	MSDC-0602K 250 mg taken once daily for 360 days MSDC-0602K: MSDC-0602K capsules	0	101	7	101	77	101