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Cysteamine Bitartrate Delayed-Release for the Treatment of NAFLD in Children (CyNCh)

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ClinicalTrials.gov Identifier: NCT01529268
Recruitment Status : Completed
First Posted : February 8, 2012
Results First Posted : September 5, 2017
Last Update Posted : September 5, 2017
Sponsor:
Collaborators:
National Center for Advancing Translational Science (NCATS)
National Cancer Institute (NCI)
Raptor Pharmaceuticals
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Nonalcoholic Fatty Liver Disease (NAFLD)
Interventions Drug: DR cysteamine bitartrate capsule
Other: DR cysteamine bitartrate placebo
Enrollment 169
Recruitment Details Patients were enrolled at 10 NASH CRN clinical centers from June 2012 to January 2014.
Pre-assignment Details  
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description

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

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
Period Title: Overall Study
Started 88 81
Completed 52-week Biopsy 71 75
Completed 76 78
Not Completed 12 3
Reason Not Completed
Lost to Follow-up             9             3
Moved             3             0
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo Total
Hide Arm/Group Description

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

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
Total of all reporting groups
Overall Number of Baseline Participants 88 81 169
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 88 participants 81 participants 169 participants
13.8  (2.9) 13.6  (2.5) 13.7  (2.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 81 participants 169 participants
Female
25
  28.4%
25
  30.9%
50
  29.6%
Male
63
  71.6%
56
  69.1%
119
  70.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 88 participants 81 participants 169 participants
American Indian/Alaska Native 5 6 11
Asian 0 2 2
Black or African-American 3 3 6
White 56 46 102
More than one race 3 1 4
Refusal/not stated 21 23 44
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 88 participants 81 participants 169 participants
88 81 169
Alanine aminotransferase  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 88 participants 81 participants 169 participants
140  (118) 103  (76) 123  (101)
Aspartate aminotransferase  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 88 participants 81 participants 169 participants
82  (71) 59  (38) 71  (59)
Weight group  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 88 participants 81 participants 169 participants
Less than or equal to 65 kg 24 23 47
>65-80 kg 14 10 24
>80 kg 50 48 98
1.Primary Outcome
Title Improvement in Nonalcoholic Fatty Liver Disease (NAFLD)
Hide Description 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.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 88 81
Measure Type: Number
Unit of Measure: participants
25 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.8 to 2.1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Hide Description 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.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 71 75
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.8  (1.8) -0.8  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments P-values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 52 weeks on treatment group and baseline value of the outcome, for outcome scores.
Statistical Test of Hypothesis P-Value 0.90
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.6 to 0.5
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Steatosis: Patients With Improvement
Hide Description Improvement in steatosis defined as any decrease in steatosis grade comparing 52-week biopsy to baseline.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 88 81
Measure Type: Number
Unit of Measure: participants
26 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Steatosis: patients with improvement
Type of Statistical Test Superiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
0.5 to 1.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Steatosis: Change in Score
Hide Description 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).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 71 75
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.3  (0.9) -0.4  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Steatosis: change in score
Type of Statistical Test Non-Inferiority or Equivalence
Comments P-values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 52 weeks on treatment group and baseline value of the outcome, for outcome scores.
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.4
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Lobular Inflammation: Patients With Improvement
Hide Description Improvement in lobular inflammation defined as any decrease in lobular inflammation grade comparing 52-week biopsy to baseline.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 88 81
Measure Type: Number
Unit of Measure: participants
32 17
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
1.1 to 2.9
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Lobular Inflammation: Change in Score
Hide Description 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).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 71 75
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.4  (0.8) -0.1  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments P-values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 52 weeks on treatment group and baseline value of the outcome, for outcome scores.
Statistical Test of Hypothesis P-Value 0.06
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Hepatocellular Ballooning: Patients With Improvement
Hide Description Improvement in hepatocellular ballooning defined as any decrease in hepatocellular ballooning score comparing 52-week biopsy to baseline.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 88 81
Measure Type: Number
Unit of Measure: participants
17 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.29
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
0.4 to 1.3
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Hepatocellular Ballooning: Change in Score
Hide Description 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).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 71 75
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.1  (0.7) -0.3  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments P-values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 52 weeks on treatment group and baseline value of the outcome, for outcome scores.
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.1 to 0.3
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Portal Inflammation: Patients With Improvement
Hide Description Improvement in portal inflammation defined as any decrease in portal inflammation score comparing 52-week biopsy to baseline.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 88 81
Measure Type: Number
Unit of Measure: participants
18 14
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
0.6 to 2.3
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Portal Inflammation: Change in Score
Hide Description 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).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 71 75
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.1  (0.6) -0.1  (0.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments P-values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 52 weeks on treatment group and baseline value of the outcome, for outcome scores.
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.2
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Fibrosis: Patients With Improvement
Hide Description Improvement in fibrosis stage defined as any decrease in fibrosis stage comparing 52-week biopsy to baseline.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis based on intention to treat; patients with missing 52-week biopsy were imputed as lack of improvement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 88 81
Measure Type: Number
Unit of Measure: participants
25 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.6 to 1.6
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Fibrosis: Change in Stage
Hide Description 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).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week biopsies (complete case analysis).
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 71 75
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.3  (0.9) -0.1  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments P-values and mean changes from baseline were calculated using ANCOVA, regressing change from baseline to 52 weeks on treatment group and baseline value of the outcome, for outcome scores.
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.1
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Resolution of NASH
Hide Description Patients with a change from a histological diagnosis of definite NASH or indeterminate for NASH to not NASH at end of treatment
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was limited to patients with a diagnosis of definite NASH at baseline.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 24 23
Measure Type: Number
Unit of Measure: participants
4 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Relative risks and p-values were calculated with the Cochran-Mantel-Haenszel chi-square tests, stratified by clinic and weight group, for binary outcomes.
Statistical Test of Hypothesis P-Value 0.29
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by clinic and weight group
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
0.4 to 18.3
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change in Serum Aminotransferase and Gamma-glutamyl Transpeptidase
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The smaller number of participants analyzed is due to missing 52-week laboratory data.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: U/L
Alanine aminotransferase -53  (88) -8  (77)
Aspartate aminotransferase -31  (52) -4  (36)
Gamma-glutamyl transpeptidase -10  (23) -1  (16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in serum alanine aminotransferase (ALT). The change in ALT is adjusted for the baseline ALT value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing change from baseline to 52 weeks in serum alanine aminotransferase on treatment group and baseline value of serum alanine aminotransferase.
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline serum alanine aminotransferase
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -24
Confidence Interval (2-Sided) 95%
-44 to -4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in serum aspartate aminotransferase (AST). The change in AST is adjusted for the baseline AST value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in serum aspartate aminotransferase on treatment group and baseline value of serum aspartate aminotransferase.
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline serum aspartate aminotransferase.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15
Confidence Interval (2-Sided) 95%
-26 to -4
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in serum gamma-glutamyl transpeptidase (GGT). The change in GGT is adjusted for the baseline GGTvalue; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in gamma-glutamyl transpeptidase on treatment group and baseline value of gamma-glutamyl transpeptidase.
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline gamma-glutamyl transpeptidase
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -7
Confidence Interval (2-Sided) 95%
-13 to -1
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change in Weight (kg)
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Smaller number of patients analyzed due to missing 52-week weight measurement.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: kg
6.3  (9.3) 7.8  (6.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in weight (kg). The change in weight is adjusted for the baseline weight value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Non-Inferiority or Equivalence
Comments P-value and adjusted difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in weight (kg) on treatment group and baseline weight (kg).
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline weight (kg).
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-4.1 to 1.1
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change in Body-mass Index
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: kg/m^2
0.8  (2.8) 1.1  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in body mass index (BMI). The change in BMI is adjusted for the baseline BMI value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks on treatment group and baseline value of the outcome.
Statistical Test of Hypothesis P-Value 0.42
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline BMI (kg/m2)
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-1.1 to 0.5
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change in Body-mass Index Z-score
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: SD
-0.1  (0.3) 0  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks on treatment group and baseline value of the outcome.
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.1 to 0.0
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change in Waist Circumference
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: cm
2.5  (7.7) 2.3  (7.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in waist circumference (cm). The change in waist circumference is adjusted for the baseline waist circumference value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in waist circumference on treatment group and baseline value of waist circumference.
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline waist circumference (cm)
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.3 to 2.6
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change in Fasting Serum Glucose
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: mg/dL
1  (12) 5  (27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in fasting serum glucose. The change in fasting serum glucose is adjusted for the baseline fasting serum glucose value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Non-Inferiority or Equivalence
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in fasting serum glucose on treatment group and baseline fasting serum glucose value.
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline serum glucose value.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -4
Confidence Interval (2-Sided) 95%
-11 to 3
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change in Fasting Insulin
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: μU/mL
6  (36) 10  (40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in fasting insulin. The change in fasting insulin is adjusted for the baseline fasting insulin value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in fasting insulin on treatment group and baseline fasting insulin.
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline fasting insulin.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -6
Confidence Interval (2-Sided) 95%
-18 to 6
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change in HOMA-IR
Hide Description (Glucose (mmol/L) x insulin (pmol/L))/22.5
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: (10E-15 mol^2)/L^2
1.4  (9.2) 3.6  (12.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in HOMA-IR. The change in HOMA-IR is adjusted for the baseline HOMA-IR value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in HOMA-IR on treatment group and baseline HOMA-IR value.
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline HOMA-IR.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-6.2 to 1.0
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change in Systolic Blood Pressure
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: mmHg
3  (12) 2  (12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in systolic blood pressure. The change in systolic blood pressure is adjusted for the baseline systolic blood pressure value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in systolic blood pressure on treatment group and baseline systolic blood pressure value.
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline systolic blood pressure.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value 1
Confidence Interval (2-Sided) 95%
-3 to 4
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change in Diastolic Blood Pressure
Hide Description [Not Specified]
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: mmHg
-1  (9) 1  (9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes in diastolic blood pressure. The change in diastolic blood pressure is adjusted for the baseline diastolic blood pressure value; therefore, the adjusted difference in mean changes is not equal to the net change.
Type of Statistical Test Superiority
Comments P-values and differences in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in diastolic blood pressure on treatment group and baseline diastolic blood pressure value.
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline diastolic blood pressure.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -1
Confidence Interval (2-Sided) 95%
-4 to 1
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Change in Pediatric Quality of Life Inventory (PedsQL) Score
Hide Description 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.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 75 77
Mean (Standard Deviation)
Unit of Measure: units on a scale
Self-reported physical health 4  (17) 5  (16)
Self-reported psychosocial health 4  (15) 5  (14)
Parent/guardian-reported physical health 4  (27) 5  (24)
Parent/guardian-reported psychosocial health 5  (18) 6  (24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes from baseline in self-reported Physical Health summary score from the Pediatric Quality of Life Inventory (PedsQL). The difference in mean changes in Physical Health summary score is adjusted for the baseline Physical Health summary score; therefore, the adjusted difference in mean changes is not equal to the net change. Higher scores indicate better health-related quality of life.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in self-reported Physical Health summary score on treatment group and baseline value of the Physical Health summary score.
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline self-reported Physical Health summary score.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -1
Confidence Interval (2-Sided) 95%
-5 to 3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes from baseline in self-reported Psychosocial Health summary score from the Pediatric Quality of Life Inventory (PedsQL). The difference in mean changes in Psychosocial Health summary score is adjusted for the baseline Psychosocial Health summary score; therefore, the adjusted difference in mean changes is not equal to the net change. Higher scores indicate better health-related quality of life.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in Pyschosocial Health summary score on treatment group and baseline Psychosocial Health summary score.
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline Psychosocial Health summary score.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -1
Confidence Interval (2-Sided) 95%
-5 to 3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes from baseline in parent/guardian-reported Physical Health summary score from the Pediatric Quality of Life Inventory (PedsQL). The difference in mean changes in parent/guardian-reported Physical Health summary score is adjusted for the baseline parent/guardian-reported Physical Health summary score; therefore, the adjusted difference in mean changes is not equal to the net change. Higher scores indicate better health-related quality of life.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in parent/guardian-reported Physical Health summary score on treatment group and baseline value of the parent/guardian-reported Physical Health summary score.
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline parent/guardian-reported Physical Health summary score.
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -2
Confidence Interval (2-Sided) 95%
-9 to 5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments Adjusted difference in mean changes from baseline in parent/guardian-reported Psychosocial Health summary score from the Pediatric Quality of Life Inventory (PedsQL). The difference in mean changes in parent/guardian-reported Psychosocial Health summary score is adjusted for the baseline parent/guardian-reported Psychosocial Health summary score; therefore, the adjusted difference in mean changes is not equal to the net change. Higher scores indicate better health-related quality of life.
Type of Statistical Test Superiority
Comments P-value and difference in mean changes from baseline were calculated using ANCOVA models, regressing changes from baseline to 52 weeks in parent/guardian-reported Psychosocial Health summary score on treatment group and baseline value of the parent/guardian-reported Psychosocial Health summary score.
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted difference in mean changes
Estimated Value -1
Confidence Interval (2-Sided) 95%
-6 to 5
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Reduction in MRI-determined Hepatic Fat Fraction
Hide Description Change from baseline in MRI Proton Density Fat Fraction (PDFF) (%).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description:

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

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
Overall Number of Participants Analyzed 38 46
Mean (Standard Deviation)
Unit of Measure: percentage of PDFF
-5.3  (7.1) -2.6  (7.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DR Cysteamine Bitartrate Capsule, DR Cysteamine Bitartrate Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.7
Estimation Comments [Not Specified]
Time Frame 52 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Hide Arm/Group Description

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

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
All-Cause Mortality
DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/88 (0.00%)      0/81 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/88 (5.68%)      4/81 (4.94%)    
Endocrine disorders     
Diabetes * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Gastrointestinal disorders     
Pain - Abdomen NOS * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Hepatobiliary disorders     
Pain - Gallbladder * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Cholecystitis * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Infections and infestations     
Infection - Appendix * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Musculoskeletal and connective tissue disorders     
Soft tissue necrosis * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Psychiatric disorders     
Mood alteration - depression * 1  1/88 (1.14%)  2 1/81 (1.23%)  1
Personality/behavioral * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
1
Term from vocabulary, CTCAE (3.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
DR Cysteamine Bitartrate Capsule DR Cysteamine Bitartrate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   62/88 (70.45%)      55/81 (67.90%)    
Cardiac disorders     
Hypertension * 1  1/88 (1.14%)  1 3/81 (3.70%)  3
Palpitations * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Ear and labyrinth disorders     
Pain - middle ear * 1  2/88 (2.27%)  2 2/81 (2.47%)  2
Endocrine disorders     
Diabetes * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Metabolic/lab - other * 1 [1]  1/88 (1.14%)  1 0/81 (0.00%)  0
Metabolic/lab - other * 1 [2]  1/88 (1.14%)  1 0/81 (0.00%)  0
Eye disorders     
Ocular - other * 1 [3]  1/88 (1.14%)  1 0/81 (0.00%)  0
Ocular surface disease * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Ocular - other * 1 [4]  0/88 (0.00%)  0 1/81 (1.23%)  1
Ocular - other (eye redness, allergies) * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Gastrointestinal disorders     
Pain - abdomen NOS * 1  11/88 (12.50%)  11 8/81 (9.88%)  9
Constipation * 1  4/88 (4.55%)  4 4/81 (4.94%)  5
Teeth * 1  2/88 (2.27%)  2 0/81 (0.00%)  0
Diarrhea * 1  12/88 (13.64%)  12 11/81 (13.58%)  13
Vomiting * 1  6/88 (6.82%)  7 9/81 (11.11%)  10
Pain - stomach * 1  4/88 (4.55%)  4 4/81 (4.94%)  4
Nausea * 1  5/88 (5.68%)  5 5/81 (6.17%)  6
Hemorrhage, GI - rectum * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
Heartburn * 1  2/88 (2.27%)  2 3/81 (3.70%)  5
Flatulence * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Enteritis * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
General disorders     
Hemorrhage - pulmonary - nose * 1 [5]  3/88 (3.41%)  5 4/81 (4.94%)  8
Fatigue * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Insomnia * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Flu-like syndrome * 1  3/88 (3.41%)  3 0/81 (0.00%)  0
Hepatobiliary disorders     
Metabolic/lab - other * 1 [6]  0/88 (0.00%)  0 1/81 (1.23%)  1
Immune system disorders     
Allergic reaction * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Rhinitis * 1  3/88 (3.41%)  3 5/81 (6.17%)  5
Allergy - other * 1 [7]  0/88 (0.00%)  0 1/81 (1.23%)  1
Infections and infestations     
Infection - skin * 1  1/88 (1.14%)  1 2/81 (2.47%)  2
Infection - urinary tract NOS * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Infection - ungual * 1 [8]  2/88 (2.27%)  2 0/81 (0.00%)  0
Fever * 1  3/88 (3.41%)  3 0/81 (0.00%)  0
Infection - pharynx * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Infection - larynx * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Infection - stomach * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Infection - middle ear (otitis media) * 1  4/88 (4.55%)  5 3/81 (3.70%)  3
Infection (middle ear) with unknown ANC * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Infection (ungual) with unknown ANC * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Infection (sinus) with unknown ANC * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Infection - upper airway NOS * 1  3/88 (3.41%)  4 3/81 (3.70%)  3
Infection - bronchus * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Infection - sinus * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Infection (documented clinically) - pharynx * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Infection - lung (pneumonia) * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Injury, poisoning and procedural complications     
Pain - bone * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Neurology - other (concussion) * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Intraop injury - liver * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Dermatology - other * 1 [9]  0/88 (0.00%)  0 1/81 (1.23%)  1
Musculoskeletal - other (ankle sprain) * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Musculoskeletal - other (wrist sprain) * 1  1/88 (1.14%)  1 1/81 (1.23%)  1
Musculoskeletal - other (finger sprain) * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Cervical spine ROM * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Metabolism and nutrition disorders     
Hypertriglyceridemia * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Musculoskeletal and connective tissue disorders     
Arthritis * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Fracture * 1  4/88 (4.55%)  4 1/81 (1.23%)  1
Pain - joint * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Bone growth - spine * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Extremity - upper * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Joint - function * 1  1/88 (1.14%)  1 3/81 (3.70%)  3
Lumbar spine ROM * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Pain (extremity - limb) * 1  3/88 (3.41%)  3 3/81 (3.70%)  4
Joint - function * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
Musculoskletal - other (spondylosis) * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Nervous system disorders     
Dizziness * 1  2/88 (2.27%)  2 1/81 (1.23%)  1
Pain - head/headache * 1  9/88 (10.23%)  9 6/81 (7.41%)  6
Neuropathy - sensory * 1  2/88 (2.27%)  2 0/81 (0.00%)  0
Psychiatric disorders     
Mood alteration - anxiety * 1  2/88 (2.27%)  2 0/81 (0.00%)  0
Mood alteration - not specified * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
Mood alteration - depression * 1  2/88 (2.27%)  2 1/81 (1.23%)  1
Mood alteration - irritability * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Renal and urinary disorders     
Cystitis * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Reproductive system and breast disorders     
Pain - testicle * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Pain - breast * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Hemorrhage, GU - vaginal * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Gynecomastia * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Irregular menses * 1  2/88 (2.27%)  2 0/81 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchospasm * 1  2/88 (2.27%)  2 1/81 (1.23%)  1
Cough * 1  6/88 (6.82%)  7 8/81 (9.88%)  10
Dyspnea * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
Pain - chest/thorax NOS * 1  4/88 (4.55%)  4 1/81 (1.23%)  2
Nasal/paranasal reactions * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Pain - chest wall * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Pneumonitis * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Pulmonary - other (cold) * 1  3/88 (3.41%)  3 3/81 (3.70%)  3
Pulmonary - other * 1 [10]  0/88 (0.00%)  0 1/81 (1.23%)  1
Pain - throat/pharynx/larynx * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
Skin and subcutaneous tissue disorders     
Alopecia * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Pruritis * 1  3/88 (3.41%)  3 0/81 (0.00%)  0
Rash * 1  4/88 (4.55%)  5 1/81 (1.23%)  2
Striae * 1  1/88 (1.14%)  1 1/81 (1.23%)  2
Hyperpigmentation * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Hypopigmentation * 1  0/88 (0.00%)  0 2/81 (2.47%)  3
Pain - skin * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Ulceration * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Urticaria * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Dermatology - other * 1 [11]  1/88 (1.14%)  1 0/81 (0.00%)  0
Dermatology - other (warts, HPV) * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
Surgical and medical procedures     
Sexual - other (orchiopexy) * 1  0/88 (0.00%)  0 1/81 (1.23%)  1
Tonsillectomy * 1  0/88 (0.00%)  0 2/81 (2.47%)  2
Vascular disorders     
Vasculitis * 1  1/88 (1.14%)  1 0/81 (0.00%)  0
1
Term from vocabulary, CTCAE (3.0)
*
Indicates events were collected by non-systematic assessment
[1]
Decrease in hemoglobin
[2]
Worsening insulin resistance
[3]
Change in prescription
[4]
Periorbital cellulitis
[5]
Nosebleed
[6]
Increase in ALT and AST
[7]
Cat allergy
[8]
Nail infection
[9]
Stepped on nail
[10]
Positive PPD, negative chest X-ray
[11]
Edematous nodular lesions with pruritus
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Laura Wilson
Organization: Johns Hopkins Data Coordinating Center
Phone: 410-955-0719
EMail: lwilson9@jhu.edu
Layout table for additonal information
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01529268     History of Changes
Other Study ID Numbers: NASH-CyNCh
U01DK061718 ( U.S. NIH Grant/Contract )
U01DK061728 ( U.S. NIH Grant/Contract )
U01DK061731 ( U.S. NIH Grant/Contract )
U01DK061732 ( U.S. NIH Grant/Contract )
U01DK061734 ( U.S. NIH Grant/Contract )
U01DK061737 ( U.S. NIH Grant/Contract )
U01DK061738 ( U.S. NIH Grant/Contract )
U01DK061730 ( U.S. NIH Grant/Contract )
U01DK061713 ( U.S. NIH Grant/Contract )
First Submitted: January 18, 2012
First Posted: February 8, 2012
Results First Submitted: April 10, 2017
Results First Posted: September 5, 2017
Last Update Posted: September 5, 2017