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A Study of IDN-6556 in Subjects With Liver Cirrhosis (LC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02230670
Recruitment Status : Completed
First Posted : September 3, 2014
Results First Posted : July 5, 2017
Last Update Posted : July 5, 2017
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Liver Cirrhosis
Hepatic Cirrhosis
Interventions Drug: IDN-6556
Drug: Placebo
Enrollment 87
Recruitment Details A total of 140 subjects from 26 US sites were screened, of whom 87 subjects were randomized. One subject randomized to placebo withdrew from the study before taking study drug. Disposition data is provided for the initial 3-month randomized, placebo-controlled phase on which the primary efficacy and safety analyses were based
Pre-assignment Details  
Arm/Group Title IDN-6556 Placebo
Hide Arm/Group Description

25 mg BID of IDN-6556

IDN-6556: 25 mg BID

Placebo BID

Placebo

Period Title: Overall Study
Started 44 42 [1]
Completed 40 34
Not Completed 4 8
Reason Not Completed
Adverse Event             1             2
Withdrawal by Subject             2             2
Physician Decision             0             1
Protocol Violation             0             1
Progression to Child-Pugh C             1             2
[1]
One subject randomized to placebo withdrew from the study before receiving any study treatment.
Arm/Group Title IDN-6556 Placebo Total
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25 mg BID of IDN-6556

IDN-6556: 25 mg BID

Placebo BID

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 44 42 86
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 86 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
  79.5%
34
  81.0%
69
  80.2%
>=65 years
9
  20.5%
8
  19.0%
17
  19.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 86 participants
Female
20
  45.5%
12
  28.6%
32
  37.2%
Male
24
  54.5%
30
  71.4%
54
  62.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 86 participants
Hispanic or Latino
6
  13.6%
11
  26.2%
17
  19.8%
Not Hispanic or Latino
38
  86.4%
30
  71.4%
68
  79.1%
Unknown or Not Reported
0
   0.0%
1
   2.4%
1
   1.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 42 participants 86 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   2.4%
1
   1.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   9.1%
2
   4.8%
6
   7.0%
White
39
  88.6%
37
  88.1%
76
  88.4%
More than one race
0
   0.0%
1
   2.4%
1
   1.2%
Unknown or Not Reported
1
   2.3%
1
   2.4%
2
   2.3%
1.Primary Outcome
Title Change From Baseline at Month 3 in cCK18/M30
Hide Description Baseline, Month 3, and change between for cCK18/M30
Time Frame 3 months
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Hide Analysis Population Description
FAS
Arm/Group Title IDN-6556 Placebo
Hide Arm/Group Description:

25 mg BID of IDN-6556

IDN-6556: 25 mg BID

Placebo BID

Placebo

Overall Number of Participants Analyzed 44 42
Median (Full Range)
Unit of Measure: U/L
Baseline
293.5
(66 to 1857)
257.5
(104 to 6994)
Month 3
288.5
(39 to 1583)
285.0
(115 to 19710)
2.Primary Outcome
Title Change From Baseline at Month 3 in cCK18/M30
Hide Description Data was log-transformed for analysis purposes
Time Frame 3 months
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Full analysis set
Arm/Group Title IDN-6556 Placebo
Hide Arm/Group Description:

25 mg BID of IDN-6556

IDN-6556: 25 mg BID

Placebo BID

Placebo

Overall Number of Participants Analyzed 44 42
Least Squares Mean (Standard Error)
Unit of Measure: U/L
Log-transformed Values -0.049  (0.057) 0.090  (0.058)
Percent (%) Relative Change -4.6  (5.9) 9.3  (5.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IDN-6556, Placebo
Comments Analysis was conducted using an ANCOVA model adjusting for baseline value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.140
Confidence Interval (2-Sided) 95%
-0.302 to 0.023
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0817
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IDN-6556, Placebo
Comments The analysis was conducted using an ANCOVA model adjusting for baseline value, baseline MELD score, and etiology. The significance was assessed using Type II Sums of Squares from this ANCOVA model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.41 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: .210
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Month 3 in MELD Score
Hide Description

The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. MELD is calculated according to the following formula:

MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43

MELD scores are reported as whole numbers, so the result of the equation above is rounded. Notes: If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0. Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (the natural logarithm of 1 is 0, and any value below 1 would yield a negative result). The higher the MELD score the more severe the disease state.

Time Frame 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title IDN-6556 Placebo
Hide Arm/Group Description:

25 mg BID of IDN-6556

IDN-6556: 25 mg BID

Placebo BID

Placebo

Overall Number of Participants Analyzed 44 42
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.10  (0.234) 0.15  (0.239)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IDN-6556, Placebo
Comments Analysis was conducted using an ANCOVA model adjusting for baseline value.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.466
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.91 to 0.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.333
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IDN-6556, Placebo
Comments BL MELD >= 15 subgroup results (N=19), as analyzed from the adjusted analysis ANCOVA model adjusting for baseline value, baseline MELD score, and etiology.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments calculated from the estimated least square means for the treatment by BL MELD category interaction term.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -2.19
Confidence Interval (2-Sided) 95%
-3.61 to -0.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IDN-6556, Placebo
Comments NASH Etiology subgroup results (N=20), as analyzed from the adjusted analysis ANCOVA model adjusting for baseline value, baseline MELD score, and etiology.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method ANCOVA
Comments calculated from the estimated least square means for the treatment by etiology interaction term.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-3.09 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.46
Estimation Comments [Not Specified]
Time Frame Adverse events were collected in a blinded fashion from baseline to Month 3. Double-blind adverse events are presented here
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title IDN-6556 (Baseline-Month 3) Placebo (Baseline-Month 3)
Hide Arm/Group Description 25 mg BID of IDN-6556 (Baseline-Month 3). Placebo BID (Baseline-Month 3)
All-Cause Mortality
IDN-6556 (Baseline-Month 3) Placebo (Baseline-Month 3)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)      0/42 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
IDN-6556 (Baseline-Month 3) Placebo (Baseline-Month 3)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/44 (13.64%)      5/42 (11.90%)    
Blood and lymphatic system disorders     
Anaemia * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Thrombocytopenia * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Gastrointestinal disorders     
Ascites * 1  0/44 (0.00%)  0 1/42 (2.38%)  1
Hepatobiliary disorders     
Hepatic cirrhosis * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Hepatorenal syndrome * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Infections and infestations     
Peritontis bacterial * 1  0/44 (0.00%)  0 1/42 (2.38%)  1
Urosepsis * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Injury, poisoning and procedural complications     
Accidential overdose * 1  0/44 (0.00%)  0 1/42 (2.38%)  1
Hip fracture * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Stoma site heamorrhage * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Metabolism and nutrition disorders     
Electrolyte imbalance * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Hyponatraemia * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Nervous system disorders     
Convulsions * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Hepatic encephalopathy * 1  1/44 (2.27%)  1 1/42 (2.38%)  1
intraventricular haemorrhage * 1  0/44 (0.00%)  0 1/42 (2.38%)  1
Respiratory, thoracic and mediastinal disorders     
Haemoptysis * 1  0/44 (0.00%)  0 1/42 (2.38%)  1
Pulmonary alveolar haemorrage * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
Respiratory failure * 1  1/44 (2.27%)  1 0/42 (0.00%)  0
1
Term from vocabulary, MedDRA (17.0)
*
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 5%
IDN-6556 (Baseline-Month 3) Placebo (Baseline-Month 3)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/44 (77.27%)      30/42 (71.43%)    
Blood and lymphatic system disorders     
oedema peripheral * 1  1/44 (2.27%)  1 4/42 (9.52%)  4
Gastrointestinal disorders     
abdominal pain * 1  3/44 (6.82%)  3 3/42 (7.14%)  3
ascites * 2  1/44 (2.27%)  2 3/42 (7.14%)  3
nausea * 1  7/44 (15.91%)  8 4/42 (9.52%)  5
vomiting * 1  5/44 (11.36%)  7 1/42 (2.38%)  1
General disorders     
arthralgia * 2  3/44 (6.82%)  3 0/42 (0.00%)  0
Infections and infestations     
urinary tract infection * 1  3/44 (6.82%)  3 1/42 (2.38%)  1
Metabolism and nutrition disorders     
fatigue * 1  4/44 (9.09%)  4 6/42 (14.29%)  7
Musculoskeletal and connective tissue disorders     
muscle spasms * 1  0/44 (0.00%)  0 3/42 (7.14%)  3
Nervous system disorders     
headache * 2  7/44 (15.91%)  8 3/42 (7.14%)  4
hepatic encephalopathy * 1  5/44 (11.36%)  7 2/42 (4.76%)  3
1
Term from vocabulary, MedDRA (17.0)
2
Term from vocabulary, MedDRA (Unspecified)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Name/Title: Jean L. Chan, MD
Organization: Conatus Pharmaceuticals
Phone: (858) 376-2632
Responsible Party: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02230670     History of Changes
Other Study ID Numbers: IDN-6556-10
First Submitted: August 28, 2014
First Posted: September 3, 2014
Results First Submitted: January 27, 2017
Results First Posted: July 5, 2017
Last Update Posted: July 5, 2017