Cysteamine Bitartrate Delayed-Release for the Treatment o... | NCT01529268

ID	Type	Link
U01DK061718	U.S. NIH Grant/Contract	View source
U01DK061728	U.S. NIH Grant/Contract	View source
U01DK061731	U.S. NIH Grant/Contract	View source
U01DK061732	U.S. NIH Grant/Contract	View source
U01DK061734	U.S. NIH Grant/Contract	View source
U01DK061737	U.S. NIH Grant/Contract	View source
U01DK061738	U.S. NIH Grant/Contract	View source
U01DK061730	U.S. NIH Grant/Contract	View source
U01DK061713	U.S. NIH Grant/Contract	View source

Name	Class
National Center for Advancing Translational Sciences (NCATS)	NIH
National Cancer Institute (NCI)	NIH
Raptor Pharmaceuticals	UNKNOWN

Label	Type	Description	Intervention Names
DR cysteamine bitartrate capsule	Active Comparator	Active DR cysteamine bitartrate capsule	Drug: DR cysteamine bitartrate capsule
DR cysteamine bitartrate placebo	Placebo Comparator	Placebo DR cysteamine bitartrate capsule	Other: DR cysteamine bitartrate placebo

Name	Type	Description	Arm Group Labels	Other Names
DR cysteamine bitartrate capsule	Drug	600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Measure	Description	Time Frame
Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)	Centrally scored and masked assessment of histologic improvement in Nonalcholic Fatty Liver Disease (NAFLD) between the baseline liver biopsy and follow-up biopsy after 52 weeks of treatment, where improvement is defined as: (1) decrease in the NAFLD Activity Score (NAS) of 2 or more and (2) no worsening of fibrosis.	52 weeks

Measure	Description	Time Frame
Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)	Change from baseline in the NAFLD Activity Score (NAS), which is a composite score equal to the sum of the steatosis grade (0-3), lobular inflammation grade (0-3), and hepatocellular ballooning grade (0-2), from centralized pathologist scoring of liver biopsies. The overall scale of the NAS is 0-8, with higher scores indicating more severe disease. The outcome measure, change from baseline in NAFLD Activity Score (NAS), has a possible range from -8 to +8, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome. Components of the NAS are scored as follows: Steatosis grade 0=<5% steatosis, 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Lobular inflammation grade=amount of lobular inflammation (combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci): 0=0, 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Hepatocellular ballooning 0=none, 1=mild, 2=more than mild.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Children age 8-17 years
Liver biopsy obtained within 90 days of screening visit and not more than 120 days before randomization
Clinical history consistent with nonalcoholic fatty liver disease (NAFLD)
Definite NAFLD based upon liver histology
No evidence of any other liver disease by clinical history or histological evaluation
A histological severity of: NAFLD Activity Score (NAS) ≥ 4.
Sexually active female participants of childbearing potential (i.e., not surgically sterile [defined as tubal ligation, hysterectomy, or bilateral oophorectomy]) must agree to utilize the same two acceptable forms of contraception from screening through completion of the study and to complete a serum pregnancy test at each study visit. The acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to screening, and barrier (condom with spermicide, diaphragm with spermicide). Sexual activity will be ascertained at each study visit for post-menarchal females and if sexually active, subject must verify use of the same 2 acceptable forms of contraception. For pre-pubescent children, a documented attestation of abstinence from their parent or guardian will be acceptable.
Participants must be able to swallow DR Cysteamine tablets with the tablet intact
Written informed consent from parent or legal guardian
Written informed assent from the child

Exclusion Criteria:

There will be no exclusion criteria based on race, ethnicity or gender.
Participants with a current history of the following conditions or any other health issues that make it unsafe for them to participate in the opinion of the Investigators:
- Inflammatory bowel disease (if currently active) or prior resection of small intestine
- Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias)
- Seizure disorder
- Active coagulopathy
- Gastrointestinal ulcers/bleeding
- Renal dysfunction with a creatinine clearance < 90 mL/min/m2
- History of active malignant disease requiring chemotherapy within the past 12 months prior to randomization
- History of significant alcohol intake (AUDIT questionnaire) or inability to quantify alcohol consumption
- Chronic use (more than 2 consecutive weeks) of medications known to cause hepatic steatosis or steatohepatitis (systemic glucocorticoids, tetracycline, anabolic steroids, valproic acid, salicylates, tamoxifen) in the past year.
- The use of other known hepatotoxins within 90 days of liver biopsy or within 120 days of randomization
- Initiation of medications with the intent to treat NAFLD/NASH in the time period following liver biopsy and prior to randomization
- History of total parenteral nutrition (TPN) use in year prior to screening
- History of bariatric surgery or planning to undergo bariatric surgery during study duration
- Clinically significant depression (patients hospitalized for suicidal ideations or suicide attempts within the past 12 months)
- Any female nursing, planning a pregnancy, known or suspected to be pregnant, or who has a positive serum pregnancy screen.
Non-compensated liver disease with any one of the following hematologic, biochemical, and serological criteria on entry into protocol:
- Hemoglobin < 10 g/dL;
- White blood cell (WBC) < 3,500 cells/mm3 of blood;
- Neutrophil count < 1,500 cells/mm3 of blood;
- Platelets < 130,000 cells/mm3 of blood;
- Direct bilirubin > 1.0 mg/dL
- Total bilirubin >3 mg/dL
- Albumin < 3.2 g/dL
- International normalized ratio (INR) > 1.4
Poorly controlled diabetes mellitus (hemoglobin A1c (HbA1c) > 9%)
Evidence of other chronic liver disease:
- Biopsy consistent with histological evidence of autoimmune hepatitis
- Serum hepatitis B surface antigen (HBsAg) positive.
- Serum hepatitis C antibody (anti-HCV) positive.
- Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 45% with histological evidence of iron overload
- Alpha-1-antitrypsin (A1AT) phenotype ZZ or SZ
- Wilson's disease
Children who are currently enrolled in a clinical trial or who received an investigational study drug within 180 days of screening or liver biopsy.
Subjects who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator.
Failure to give informed consent

Name	Affiliation	Role
Edward Doo, MD	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of California, San Diego		San Diego	California	92103	United States
University of California, San Francisco

PubMed Identifier	Type	Citation	Retractions
38055641	Derived	Jain AK, Buchannan P, Yates KP, Belt P, Schwimmer JB, Rosenthal P, Murray KF, Molleston JP, Scheimann A, Xanthakos SA, Behling CA, Hertel P, Nilson J, Neuschwander-Tetri BA, Tonascia J, Vos MB; Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Nutrition assessment and MASH severity in children using the Healthy Eating Index. Hepatol Commun. 2023 Dec 7;7(12):e0320. doi: 10.1097/HC9.0000000000000320. eCollection 2023 Dec 1.
27569726	Derived

Label	URL
Nonalcoholic Steatohepatitis Clinical Research Network Centers	View source

ID	Title	Description
FG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

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

Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)

Centrally scored and masked assessment of histologic improvement in Nonalcholic Fatty Liver Disease (NAFLD) between the baseline liver biopsy and follow-up biopsy after 52 weeks of treatment, where improvement is defined as: (1) decrease in the NAFLD Activity Score (NAS) of 2 or more and (2) no worsening of fibrosis.

Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG00088 OG00181

Title

Denominators

Categories

Title	Measurements
	OG00025 OG00118

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		Cochran-Mantel-Haenszel		0.34		Risk Ratio (RR)	1.3			2-Sided	95	0.8	2.1					Superiority	Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.

Secondary

Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)

Change from baseline in the NAFLD Activity Score (NAS), which is a composite score equal to the sum of the steatosis grade (0-3), lobular inflammation grade (0-3), and hepatocellular ballooning grade (0-2), from centralized pathologist scoring of liver biopsies. The overall scale of the NAS is 0-8, with higher scores indicating more severe disease. The outcome measure, change from baseline in NAFLD Activity Score (NAS), has a possible range from -8 to +8, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome. Components of the NAS are scored as follows: Steatosis grade 0=<5% steatosis, 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Lobular inflammation grade=amount of lobular inflammation (combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci): 0=0, 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Hepatocellular ballooning 0=none, 1=mild, 2=more than mild.

The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Steatosis: Patients With Improvement

Improvement in steatosis defined as any decrease in steatosis grade comparing 52-week biopsy to baseline.

Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Secondary

Steatosis: Change in Score

Change from baseline in steatosis score. Steatosis score is based on central pathologist grading of liver biopsies: 0=<5% steatosis; 1=5-33% steatosis, 2=34-66% steatosis, 3=>66% steatosis. Change in steatosis score has a possible range of -3 to +3, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Lobular Inflammation: Patients With Improvement

Improvement in lobular inflammation defined as any decrease in lobular inflammation grade comparing 52-week biopsy to baseline.

Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Secondary

Lobular Inflammation: Change in Score

Change from baseline in lobular inflammation score. The amount of lobular inflammation is based on central pathologist grading of liver biopsies, and combines mononuclear, fat granulomas, and polymorphonuclear (pmn) foci: 0=none; 1=<2 under 20x magnification, 2=2-4 under 20x magnification, 3=>4 under 20x magnification. Change in lobular inflammation score has a possible range of -3 to +3, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Hepatocellular Ballooning: Patients With Improvement

Improvement in hepatocellular ballooning defined as any decrease in hepatocellular ballooning score comparing 52-week biopsy to baseline.

Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Secondary

Hepatocellular Ballooning: Change in Score

Change from baseline in hepatocellular ballooning score. The amount of hepatocellular ballooning is based on central pathologist grading of liver biopsies: 0=none; 1=few ballooned hepatocytes, 2=many ballooned hepatocytes. Change in hepatocellular ballooning score has a possible range of -2 to +2, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Portal Inflammation: Patients With Improvement

Improvement in portal inflammation defined as any decrease in portal inflammation score comparing 52-week biopsy to baseline.

Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Secondary

Portal Inflammation: Change in Score

Change from baseline in portal inflammation score. The amount of portal inflammation is based on central pathologist grading of liver biopsies: 0=none; 1=mild, 2=more than mild. Change in portal inflammation score has a possible range of -2 to +2, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Fibrosis: Patients With Improvement

Improvement in fibrosis stage defined as any decrease in fibrosis stage comparing 52-week biopsy to baseline.

Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Secondary

Fibrosis: Change in Stage

Change from baseline in fibrosis stage. The amount of fibrosis is based on central pathologist grading of liver biopsies: 0=none; 1a=mild, zone 3 perisinusoidal, 1b=moderate, zone 3, perisinusoidal, 1c=portal/periportal only, 2=zone 3 and periportal, any combination, 3=bridging, 4=cirrhosis. Fibrosis stages 1a, 1b, 1c recoded as 1, so the possible range of values for fibrosis stage was 0-4. Change in fibrosis stage has a possible range of -4 to +4, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome (no improvement).

The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Resolution of NASH

Patients with a change from a histological diagnosis of definite NASH or indeterminate for NASH to not NASH at end of treatment

Analysis was limited to patients with a diagnosis of definite NASH at baseline.

Posted

Number

participants

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Secondary

Change in Serum Aminotransferase and Gamma-glutamyl Transpeptidase

The smaller number of participants analyzed is due to missing 52-week laboratory data.

Posted

Mean

Standard Deviation

U/L

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Weight (kg)

Smaller number of patients analyzed due to missing 52-week weight measurement.

Posted

Mean

Standard Deviation

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Body-mass Index

Posted

Mean

Standard Deviation

kg/m^2

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Body-mass Index Z-score

Posted

Mean

Standard Deviation

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Waist Circumference

Posted

Mean

Standard Deviation

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Fasting Serum Glucose

Posted

Mean

Standard Deviation

mg/dL

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Fasting Insulin

Posted

Mean

Standard Deviation

μU/mL

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in HOMA-IR

(Glucose (mmol/L) x insulin (pmol/L))/22.5

Posted

Mean

Standard Deviation

(10E-15 mol^2)/L^2

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Systolic Blood Pressure

Posted

Mean

Standard Deviation

mmHg

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Diastolic Blood Pressure

Posted

Mean

Standard Deviation

mmHg

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants	OG000

Secondary

Change in Pediatric Quality of Life Inventory (PedsQL) Score

Pediatric Quality of Life Inventory (PedsQL) version 4.0 is completed by both the child and parent/caregiver, and is composed of 23 items comprising 4 dimensions: Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Scores are transformed on a scale from 0 to 100, with higher scores indicating better health-related quality of life. Physical Health Summary Score =Physical Functioning Scale Score. Psychosocial Health Summary Score = Sum of items over the number of items answered in the Emotional, Social, and School Functioning Scales.

Posted

Mean

Standard Deviation

units on a scale

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Secondary

Reduction in MRI-determined Hepatic Fat Fraction

Change from baseline in MRI Proton Density Fat Fraction (PDFF) (%).

The smaller number of observations is because MRI was an optional procedure. This is the number with MRI exams at both baseline and 52 weeks.

Posted

Mean

Standard Deviation

percentage of PDFF

52 weeks

ID	Title	Description
OG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
OG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pain - abdomen NOS	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG00011 events11 affected88 at risk EG0019 events8 affected81 at risk
Ocular - other	Eye disorders	CTCAE (3.0)	Non-systematic Assessment	Change in prescription	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Allergic reaction	Immune system disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Rhinitis	Immune system disorders	CTCAE (3.0)	Non-systematic Assessment		EG0003 events3 affected88 at risk EG0015 events5 affected81 at risk
Allergy - other	Immune system disorders	CTCAE (3.0)	Non-systematic Assessment	Cat allergy	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Mood alteration - anxiety	Psychiatric disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0010 events0 affected81 at risk
Arthritis	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0011 events1 affected81 at risk
Fracture	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0004 events4 affected88 at risk EG0011 events1 affected81 at risk
Constipation	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0004 events4 affected88 at risk EG0015 events4 affected81 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0007 events6 affected88 at risk EG00110 events8 affected81 at risk
Cystitis	Renal and urinary disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Teeth	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0010 events0 affected81 at risk
Diabetes	Endocrine disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG00012 events12 affected88 at risk EG00113 events11 affected81 at risk
Dizziness	Nervous system disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0011 events1 affected81 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Pain - head/headache	Nervous system disorders	CTCAE (3.0)	Non-systematic Assessment		EG0009 events9 affected88 at risk EG0016 events6 affected81 at risk
Vomiting	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0007 events6 affected88 at risk EG00110 events9 affected81 at risk
Pain - stomach	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0004 events4 affected88 at risk EG0014 events4 affected81 at risk
Nausea	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0005 events5 affected88 at risk EG0016 events5 affected81 at risk
Pruritis	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0003 events3 affected88 at risk EG0010 events0 affected81 at risk
Rash	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0005 events4 affected88 at risk EG0012 events1 affected81 at risk
Striae	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0012 events1 affected81 at risk
Infection - skin	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0012 events2 affected81 at risk
Pain - testicle	Reproductive system and breast disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Vasculitis	Vascular disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - urinary tract NOS	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Mood alteration - not specified	Psychiatric disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Mood alteration - depression	Psychiatric disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0011 events1 affected81 at risk
Mood alteration - irritability	Psychiatric disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - ungual	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment	Nail infection	EG0002 events2 affected88 at risk EG0010 events0 affected81 at risk
Hemorrhage - pulmonary - nose	General disorders	CTCAE (3.0)	Non-systematic Assessment	Nosebleed	EG0005 events3 affected88 at risk EG0018 events4 affected81 at risk
Pain - joint	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Pain - chest/thorax NOS	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0004 events4 affected88 at risk EG0012 events1 affected81 at risk
Pain - breast	Reproductive system and breast disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Metabolic/lab - other	Hepatobiliary disorders	CTCAE (3.0)	Non-systematic Assessment	Increase in ALT and AST	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Bone growth - spine	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Hemorrhage, GI - rectum	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Hemorrhage, GU - vaginal	Reproductive system and breast disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Hypertension	Cardiac disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0013 events3 affected81 at risk
Gynecomastia	Reproductive system and breast disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Heartburn	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0015 events3 affected81 at risk
Hyperpigmentation	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Hypopigmentation	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0013 events2 affected81 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Fatigue	General disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Extremity - upper	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Fever	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0003 events3 affected88 at risk EG0010 events0 affected81 at risk
Flatulence	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Metabolic/lab - other	Endocrine disorders	CTCAE (3.0)	Non-systematic Assessment	Decrease in hemoglobin	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - pharynx	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Infection - larynx	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Infection - stomach	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Insomnia	General disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Irregular menses	Reproductive system and breast disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0010 events0 affected81 at risk
Joint - function	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0013 events3 affected81 at risk
Lumbar spine ROM	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Nasal/paranasal reactions	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - middle ear (otitis media)	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0005 events4 affected88 at risk EG0013 events3 affected81 at risk
Pain - middle ear	Ear and labyrinth disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0012 events2 affected81 at risk
Pain - skin	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Pain - chest wall	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Pain (extremity - limb)	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0003 events3 affected88 at risk EG0014 events3 affected81 at risk
Pain - bone	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Palpitations	Cardiac disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Ocular surface disease	Eye disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Ocular - other	Eye disorders	CTCAE (3.0)	Non-systematic Assessment	Periorbital cellulitis	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Ulceration	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Infection (middle ear) with unknown ANC	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection (ungual) with unknown ANC	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Infection (sinus) with unknown ANC	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Urticaria	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - upper airway NOS	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0004 events3 affected88 at risk EG0013 events3 affected81 at risk
Sexual - other (orchiopexy)	Surgical and medical procedures	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Pulmonary - other (cold)	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0003 events3 affected88 at risk EG0013 events3 affected81 at risk
Infection - bronchus	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Dermatology - other	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment	Edematous nodular lesions with pruritus	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Flu-like syndrome	General disorders	CTCAE (3.0)	Non-systematic Assessment		EG0003 events3 affected88 at risk EG0010 events0 affected81 at risk
Dermatology - other (warts, HPV)	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - sinus	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Infection (documented clinically) - pharynx	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - lung (pneumonia)	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Enteritis	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Pulmonary - other	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment	Positive PPD, negative chest X-ray	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Metabolic/lab - other	Endocrine disorders	CTCAE (3.0)	Non-systematic Assessment	Worsening insulin resistance	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Neuropathy - sensory	Nervous system disorders	CTCAE (3.0)	Non-systematic Assessment		EG0002 events2 affected88 at risk EG0010 events0 affected81 at risk
Neurology - other (concussion)	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Joint - function	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Intraop injury - liver	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Pain - throat/pharynx/larynx	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Dermatology - other	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment	Stepped on nail	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Musculoskeletal - other (ankle sprain)	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Musculoskeletal - other (wrist sprain)	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Musculoskeletal - other (finger sprain)	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Cervical spine ROM	Injury, poisoning and procedural complications	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Musculoskletal - other (spondylosis)	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment		EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Tonsillectomy	Surgical and medical procedures	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0012 events2 affected81 at risk
Ocular - other (eye redness, allergies)	Eye disorders	CTCAE (3.0)	Non-systematic Assessment		EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk

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

ID	Title	Description
BG000	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
BG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline
BG002	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	DR Cysteamine Bitartrate Capsule	Active DR cysteamine bitartrate capsule DR cysteamine bitartrate capsule: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline	0	88	5	88	62	88
EG001	DR Cysteamine Bitartrate Placebo	Placebo DR cysteamine bitartrate capsule DR cysteamine bitartrate placebo: ◦ 600 mg/day (four 75 mg capsules twice daily) for patients ≤ 65 kg at baseline 750 mg/day (five 75 mg capsules twice daily) for patients >65 - 80 kg at baseline 900 mg/day (six 75 mg capsules twice daily) for patients >80 kg at baseline	0	81	4	81	55	81

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pain - Gallbladder	Hepatobiliary disorders	CTCAE (3.0)	Non-systematic Assessment	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Infection - Appendix	Infections and infestations	CTCAE (3.0)	Non-systematic Assessment	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Mood alteration - depression	Psychiatric disorders	CTCAE (3.0)	Non-systematic Assessment	EG0002 events1 affected88 at risk EG0011 events1 affected81 at risk
Diabetes	Endocrine disorders	CTCAE (3.0)	Non-systematic Assessment	EG0001 events1 affected88 at risk EG0011 events1 affected81 at risk
Cholecystitis	Hepatobiliary disorders	CTCAE (3.0)	Non-systematic Assessment	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Soft tissue necrosis	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Non-systematic Assessment	EG0000 events0 affected88 at risk EG0011 events1 affected81 at risk
Pain - Abdomen NOS	Gastrointestinal disorders	CTCAE (3.0)	Non-systematic Assessment	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk
Personality/behavioral	Psychiatric disorders	CTCAE (3.0)	Non-systematic Assessment	EG0001 events1 affected88 at risk EG0010 events0 affected81 at risk