Clinical Trial Results:
An Open-Label Extension Study to Assess the Safety of GSK1605786A in Subjects with Crohn’s Disease
Summary
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EudraCT number |
2010-022384-35 |
Trial protocol |
DE BE SE GB CZ DK HU GR AT PL ES PT EE IT SK BG |
Global end of trial date |
29 Oct 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
10 Mar 2016
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First version publication date |
05 Jun 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CCX114644
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01318993 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, +1 8664357343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, +1 8664357343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Mar 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Oct 2013
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the safety and tolerability of long-term treatment with GSK1605786A in subjects with Crohn’s disease.
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Protection of trial subjects |
Women of child-bearing potential were excluded unless they agreed to take adequate contraceptive measures.
Subjects with known hepatic disease and / or biliary dysfunction were excluded.
Liver chemistry stopping criteria were implemented in alignment with premarketing clinical liver safety guidance.
Withdrawal criteria were implemented for those developing prolongation of the QTc interval.
Background medications to manage Crohn’s Disease were permitted.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Apr 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Estonia: 1
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Country: Number of subjects enrolled |
Denmark: 13
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Country: Number of subjects enrolled |
France: 22
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Country: Number of subjects enrolled |
Germany: 32
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Country: Number of subjects enrolled |
Hong Kong: 1
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Israel: 6
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Country: Number of subjects enrolled |
Japan: 23
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Country: Number of subjects enrolled |
Korea, Republic of: 9
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Country: Number of subjects enrolled |
New Zealand: 3
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Country: Number of subjects enrolled |
Slovakia: 4
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Country: Number of subjects enrolled |
Poland: 8
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Country: Number of subjects enrolled |
South Africa: 4
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Country: Number of subjects enrolled |
Spain: 3
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Country: Number of subjects enrolled |
Sweden: 5
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Country: Number of subjects enrolled |
Switzerland: 2
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Country: Number of subjects enrolled |
Ukraine: 1
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Country: Number of subjects enrolled |
United Kingdom: 16
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Country: Number of subjects enrolled |
United States: 107
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Country: Number of subjects enrolled |
Australia: 23
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Country: Number of subjects enrolled |
Austria: 4
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Country: Number of subjects enrolled |
Belgium: 24
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Country: Number of subjects enrolled |
Canada: 53
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Country: Number of subjects enrolled |
Czech Republic: 29
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Worldwide total number of subjects |
398
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EEA total number of subjects |
166
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
391
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were eligible to enter the study if they completed the placebo-controlled induction study CCX114151; completed the maintenance study CCX114157 at Week 52; or withdrew from the maintenance study CCX114157. | ||||||||||||||||||||||
Pre-assignment
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Screening details |
All participants entered the study at a Baseline visit, Week 0, and received GSK1605786A 500 milligrams (mg), twice daily (BID) for 216 weeks. | ||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Arms
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Arm title
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GSK1605786A 500 mg BID | ||||||||||||||||||||||
Arm description |
Participants received two GSK1605786A 250 milligram (mg), oral capsules twice daily (BID), once in the morning and once in the evening, for 216 weeks. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
GSK1605786A
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
500 mg twice daily, oral administration
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
GSK1605786A 500 mg BID
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Reporting group description |
Participants received two GSK1605786A 250 milligram (mg), oral capsules twice daily (BID), once in the morning and once in the evening, for 216 weeks. |
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End point title |
Number of participants with any adverse event (AE) and any serious adverse event (SAE) [1] | ||||||||||||
End point description |
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. The Safety population consisted of all participants who enrolled in the study except those who did not take >=1 dose of investigational product.
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End point type |
Primary
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End point timeframe |
From the start of study medication until the follow-up visit (up to Week 112).
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistics for this endpoint. |
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Notes [2] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Change from Baseline measurements in SBP and DBP were assessed at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 112
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Notes [3] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in heart rate (HR) | ||||||||||||||||||||||||||||||||
End point description |
Heart Rate (HR) values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Change from Baseline in HR was assessed at Week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 112
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Notes [4] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Number of participants with shifts from Baseline for the indicated hematology parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Hematology parameters measured included platelets, neutrophils (NL), lymphocytes, monocytes, eosinophils, basophils, hematocrit, band cells, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count, and segmented (seg) NL. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated hematology parameters data reference range shifts from Baseline (defined as shift to low, shift to normal or no change, shift to high) until 4 weeks post treatment are presented. A value of 99999 is used where no participants were analyzed for the indicated category therefore there is no data to present.
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End point type |
Secondary
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End point timeframe |
From Baseline until Week 112
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Notes [5] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Number of participants with shifts from Baseline for the indicated clinical chemistry parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical chemistry parameters included platelets, total protein, phosphorous, albumin, sodium, potassium, chloride, calcium, glucose, gamma-glutamyl transferase, total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/urea, creatinine, uric acid, bicarbonate, lactate dehydrogenase, cholesterol, and creatine kinase. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated clinical chemistry parameters' data refernce range shifts from Baseline (defined as shift to low, shift to normal or no change, or shift to high) until 4 weeks post-treatment are presented. A value of 99999 is used where no participants were analyzed for the indicated category therefore there is no data to present.
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End point type |
Secondary
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End point timeframe |
From Baseline until Week 112
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Notes [6] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in ALT, AST, ALP, and gamma-glutamyl transferase (GGT) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Changes in Baseline in Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the timepoint indicated minus the value at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 112
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Notes [7] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in total bilirubin | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Changes from Baseline in total bilirubin (TB) was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the timepoint indicated minus the value at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 112
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Notes [8] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in albumin | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from Baseline in albumin was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the timepoint indicated minus the value at Baseline. A value of 99999 is used to indicate too few participants were analyzed to determine a standard deviation therefore there is no data to present.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 112
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Notes [9] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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End point title |
Number of participants with the indicated change from Baseline in corrected QT interval (QTc) value | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
QTc is the corrected QT interval as measured by the electrocardiogram (ECG). ECG parameters including the change from Baseline in the QTc interval values QTcF and QTcB were summarised. The QTcF is Fridericia’s formula and defined as the QT interval/cubed root of the R-R interval. The QTcB is the Bazett’s formula defined as the QT/squared root of the R-R interval. The number of participants with change from Baseline in the QTcF and QTcB intervals of >30, 30-<60 and >=60 milliseconds were assesed at Week 24, 48, 72 and Week 108. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24, 48, 72 and Week 108
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Notes [10] - Safety Population. Only participants available at the specified time points were analyzed (n=X). |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up visit (up to 112 weeks).
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Adverse event reporting additional description |
On-treatment SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who enrolled in the study except those who did not take at least one dose of investigational product.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
GSK1605786A 500 mg BID
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Reporting group description |
Participants received two GSK1605786A 250 milligram (mg), oral capsules twice daily (BID), once in the morning and once in the evening, for 216 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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10 Feb 2011 |
To clarify in study description that subjects who withdraw early from the placebo-controlled maintenance study, CCX114157, due to worsening of Crohn’s disease requiring a treatment change, may also be eligible for the open-label extension study. Addition of a new author, Jatin Patel, To add contact details for David J Chang as Medical Monitor,
To delete abbreviations not referenced in the protocol, to clarify that subjects can enter Study CCX114644 if they complete Study CCX114151 and do not achieve clinical response (CDAI >=100 point decrease) or remission (CDAI < 150) or they complete any other GSK-sponsored induction study of GSK1605786A as designated by the sponsor.
To specify that study will be conducted for 108 weeks with amendment of study duration to be considered following results of Study CCX114151, to amend wording for CDAI assessments every 3 months to every 12 weeks for consistency within the protocol
To amend other endpoints for assessment of effectiveness to include the key outcome measures of proportion of subjects in remission(CDAI < 150), proportion of subjects in remission for subjects in remission at baseline, proportion of subjects in remission for subjects not in remission at baseline, and to remove endpoints of remission and response by previous study and include as subgroup analyses; to clarify that response will be measured relative to baseline of previous study, to correct typographical errors to specify 108 weeks rather than 104 weeks or Week 108 rather than Week 104, to amend wording of exclusion criterion #2 to clarify testing requirement for anti-tTG antibodies. To amend wording of exclusion criterion #3 to clarify fixed symptomatic stenoses or strictures of small bowel or colon, to include new exclusion criterion #7 to exclude subjects who have demonstrated safety or tolerability issues which were possibly related to study treatment(in the investigator’s opinion) during participation in a previous clinical study with GSK1605786A. |
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10 Feb 2011 |
To clarify that subjects may be enrolled in the study prior to receiving baseline results for LFTs and anti-tTG antibodies (if applicable). Subjects who fulfill these exclusion criteria should be withdrawn due to inability to meet continuation criteria and recorded as screen failures, To include a withdrawal criterion at Week 12 based on investigator assessment that subject is not receiving clinical benefit , to remove reference to randomised subjects, randomisation code or treatment groups made as typographical errors, to clarify text on procedures for an Early Withdrawal visit, to include wording to direct investigators to the Study Procedures Manual for details on Investigational Product, to include immunisation with live vaccines as prohibited therapy
To clarify requirements for permitted medications, including allowance for steroid taper and additional use of corticosteroids, 5-ASAs, opioid analgesics and paracetamol/acetaminophen (including correction of daily allowed dose to <=2 g/day) and inclusion of treatment for fistulae under permitted medications section, to make the following corrections or amendments to the Time and Events schedule: Correction of visit numbers, as Visit 12 had been replicated in error,Expansion of footnote to clarify only LFTs are assessed at certain visits,Addition of 12 lead ECG at Week 72 and deletion at Weeks 12, 60 and 84, Addition of haematology assessment at Week 96, Deletion of pregnancy testing at Weeks 16, 24, 32, 40 and 48, consistent with initial testing every 4 weeks, and then every 8 weeks after Week 20 and every 12 weeks after Week 60; Amendment of footnote to specify home pregnancy testing every 4 weeks after Week 60
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10 Feb 2011 |
Addition of CRP assessment at Weeks 8, 72 and 96 and at Early Withdrawal and Follow-up visits to align with CDAI assessments
Deletion of assessment of fistula closure at Weeks 12, 60 and 84 and addition of assessment of fistula closure at Week 0 (this is not a repeated assessment but carry over from Study CCX114151 Week 12 assessment or end of study visit from any other preceding study of GSK1605786A), Weeks 72 and 108, Addition of * to pregnancy test at Week 0, indicating that the test is not repeated but the result is carried over from the preceding study of GSK1605786A, Inclusion of test for coeliac disease at baseline if indicated and corresponding footnote to specify that testing should be performed upon suspicion of coeliac disease
Inclusion of Week 12 investigator assessment of clinical benefit, Amendment of timepoints for assessment of IBDQ, SF-36, EQ5D, WPAI-CD, disability and resource utilisation from Weeks 60 and 84 to Weeks 48 and 72 in Time and Events schedule; Inclusion in footnote that Week 0 disability assessment will not be available for subjects entering from a prior induction study and is not required, To amend timepoints for efficacy, safety and health outcomes assessments in protocol text to correspond with timepoints and changes in timepoints in the Time and Events schedule detailed above, To clarify that the treatment allocation from the previous study will not be available prior to enrolment, To remove the requirement for locally determined haematocrit values for CDAI calculation, To clarify timings for adverse event reporting and wording regarding serious adverse events as reported, To clarify wording for frequency of assessment of LFTs, To include assessment of concomitant medications and CRP in Follow Up visit, To include response and remission status at end of previous induction study as a subgroup analysis with clarification that response will be measured relative to baseline of previous study |
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10 Feb 2011 |
To incorporate revisions into description of efficacy analyses to correspond with changes to endpoints
To amend CDAI in Appendix 4 to reflect that investigator assessments should be performed based on findings on day of examination
To include correct version of IBDQ in Appendix 5
To correct other minor typographical errors in the protocol
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02 Aug 2011 |
To update information on sponsor departmental information
To update abbreviations to include revised information
To clarify that subjects who completed Study CCX114643 are not eligible to participate in this study
To include additional secondary objectives of assessment of activity impairment, unemployment and disability rates and biomarkers of inflammation to clarify that these evaluations are secondary objectives of this study
To include exploratory objective of assessment of fistula closure to clarify that this will be an exploratory objective of this study.
To clarify for secondary endpoints that changes in body weight and temperature will be performed only in relation to CDAI scoring and not as separate assessments
To clarify that changes in CRP concentrations as a biomarker of inflammation will be assessed as an endpoint
To amend Inclusion Criteria to include updated criteria for acceptable contraceptive methods of birth control according to sponsor standards
To amend Exclusion Criteria
• To clarify criteria for fixed symptomatic stenoses and stricture
• To include use of prohibited medications at baseline and throughout the study to ensure subject safety.
To update withdrawal and stopping criteria and testing procedures for liver chemistry abnormalities and ECG findings to be consistent with revisions to GSK standard withdrawal criteria
To clarify that the Investigator should conduct a Follow-up visit in addition to an Early Withdrawal visit for safety follow up
To clarify that prohibited medications should not be taken throughout the study and that use of stable doses of Crohn’s disease medications ongoing from a previous study are permissible
To include use of digoxin or related cardiac glycosides (e.g digitoxin, deslanoside, lanatoside C, metildigoxin) as a prohibited medication
To correct typographical errors in Time and Events table and to amend assessments to be consistent with protocol content.
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02 Aug 2011 |
To extend visit windows with longer intervals between visits to allow flexibility in scheduling
To clarify that subjects should initiate study drug administration the evening of the day of the baseline (Week 0) visit
To provide additional clarification regarding reporting of worsening of Crohn’s disease as an AE
To include information on reporting and analyses of Disease-related events common in Crohn’s disease for consistency with new FDA safety reporting guidance. Protocol-specified events related to worsening of Crohn’s disease will not be reported as SAEs
To delete concomitant medications as a safety outcome
To provide additional clarification on data handling
To include additional information on analyses of components of SF-36v2 and disability benefit data
To provide additional clarification on IDMC purpose and safety review
To amend CDAI to clarify that Investigator should assess symptoms/findings for subject based on current conditions and fever should be documented if present over the past week
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19 Mar 2013 |
To amend the study duration to 216 weeks, to revise the list of authors, to revise sponsor address and medical monitor contact information, to correct typographical errors, to consistently define draining fistulae as “open.”
To indicate that in 2012, GSK1605786A received approval for the generic name vercirnon, to remove information concerning the method of confirming male partner sterilization from the protocol to the Study Procedure Manual, to remove the exclusion prohibiting subjects with fistulae likely to require surgery from entering the study, to clarify that subjects who have been withdrawn early from study CCX114157 due to disease worsening and have received, or are receiving, certain rescue treatments shall be excluded from entry into study CCX114644, to clarify that enteral or parenteral nutritional supplementation to treat malnutrition is permitted, to clarify that any biologic or investigational agent, including – but not limited to - janus kinase inhibitors, vedolizumab and ustekinumab are prohibited medications, to revise the Time & Events table to provide for ongoing assessments from week 108 to week 216, to extend the visit window for visits from week 16 onward, to clarify the definition of the safety population, to clarify the analysis of data by subgroups, to clarify the purpose of the interim analyses that will be performed, to clarify the definition of baseline for statistical analysis purposes, to clarify how the extent of treatment exposure will be defined and summarized. To clarify that the incidence rate of adverse events will be summarized by overall duration of exposure as well as by 6-month intervals of exposure.
To clarify that ECG data will be summarized separately for data calculated manually and by machine.
To clarify the efficacy analyses that will be performed based on CDAI score and fistulae closure.
To clarify how the CRP concentration data will be summarized and analyzed for statistical purposes.
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |