Clinical Trial Results:
Changes in bile acid homeostasis and stool habits after cholecystectomy
Summary
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EudraCT number |
2016-004692-53 |
Trial protocol |
DK |
Global end of trial date |
15 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jun 2021
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First version publication date |
20 Jun 2021
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Other versions |
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 |
SJ-434
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03168555 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Zealand University Hospital
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Sponsor organisation address |
Lykkebaekvej 1, DK-Koege, Denmark, 4600
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Public contact |
Department of Medicine, Zealand University Hospital Køge, 0045 47322400, chrbo@regionsjaelland.dk
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Scientific contact |
Department of Medicine, Zealand University Hospital Køge, 0045 47322400, chrbo@regionsjaelland.dk
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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 |
03 Mar 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 May 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
15 May 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Investigate changes in hormonal regulation (particularly by FGF19 and 7α-hydroxy-4-cholesten-3-one) and composition of the bile acid pool before and after elective cholecystectomy to deem the role of the intact gall bladder.
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Protection of trial subjects |
N/A
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 May 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Denmark: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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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) |
20
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
Pre-assignment
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Screening details |
- | ||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
23 | ||||||||||||||
Intermediate milestone: Number of subjects |
Completed study visit 1 (pre-op): 22
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Number of subjects completed |
22 | ||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Intercurrent disease, cholecystectomy cancelled: 1 | ||||||||||||||
Period 1
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Period 1 title |
Pre-operative study visit
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
N/A
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Arms
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Arm title
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Meal with chenodeoxycholic acid | ||||||||||||||
Arm description |
Solid study meal with 1,250 mg chenodeoxycholic acid | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
chenodeoxycholic acid
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Investigational medicinal product code |
ATC: A05AA01
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Other name |
CDCA, 3 alpha- 7 alpha dihydroxycholic acid, Chendiol, Xenbilox
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
1,250 mg single dose (5 capsules of 25g mg)
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 23 patients enrolled, one patient withdrew from the study before study visit one, and therefore did not start the baseline periode |
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Period 2
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Period 2 title |
Post-operative study visit
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Meal with chenodeoxycholic acid | ||||||||||||||
Arm description |
Solid study meal with 1,250 mg chenodeoxycholic acid | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
chenodeoxycholic acid
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Investigational medicinal product code |
ATC: A05AA01
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Other name |
CDCA, 3 alpha- 7 alpha dihydroxycholic acid, Chendiol, Xenbilox
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
1,250 mg single dose (5 capsules of 25g mg)
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Baseline characteristics reporting groups
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Reporting group title |
Pre-operative study visit
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Meal with chenodeoxycholic acid
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Reporting group description |
Solid study meal with 1,250 mg chenodeoxycholic acid | ||
Reporting group title |
Meal with chenodeoxycholic acid
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Reporting group description |
Solid study meal with 1,250 mg chenodeoxycholic acid |
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End point title |
150 minute increment in stimulated FGF19 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Comparison of visit 1 (pre-operative) with visit 2 (post-operative)
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Statistical analysis title |
Wilcoxon signed rank test | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.03 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Median difference (net) | ||||||||||||
Confidence interval |
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End point title |
Change in fasting C4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Comparing visit 2 with visit 1
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Statistical analysis title |
paired t-test (of lognormalized base values) | ||||||||||||
Statistical analysis description |
paired t-test (of lognormalized base values)
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Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [1] | ||||||||||||
P-value |
= 0.63 | ||||||||||||
Method |
Paired t-test | ||||||||||||
Confidence interval |
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Notes [1] - paired t-test (of lognormalized base values) |
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End point title |
Change in total area under the curve of stimulated C4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
comparing visit 1 with visit 2
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Statistical analysis title |
paired t-test (of lognormalized base values) | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
Paired t-test | ||||||||||||
Confidence interval |
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End point title |
Change in fasting FGF19 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
comparing viist 1 with visit 2
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Statistical analysis title |
paired t-test (of lognormalized base values) | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.29 | ||||||||||||
Method |
Paired t-test | ||||||||||||
Confidence interval |
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End point title |
Change in total area under the curve of stimulated chenodeoxycholic acid | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
comparing viist 1 with visit 2
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Statistical analysis title |
Wilcoxon paired signed rank test | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.22 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Change in mean stools per day | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
comparing viist 1 with visit 2
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Statistical analysis title |
Wilcoxon paired signed rank test | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.73 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Change in stool consistency | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
comparing viist 1 with visit 2
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Statistical analysis title |
Wilcoxon paired signed rank test | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.8 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Change in plasma triglycerides | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
comparing viist 1 with visit 2
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Statistical analysis title |
Wilcoxon paired signed rank test | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.32 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Change in total area under the curve of stimulated FGF19 | ||||||||||||
End point description |
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End point type |
Post-hoc
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End point timeframe |
comparing viist 1 with visit 2
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Statistical analysis title |
paired t-test (of lognormalized base values) | ||||||||||||
Comparison groups |
Meal with chenodeoxycholic acid v Meal with chenodeoxycholic acid
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Number of subjects included in analysis |
36
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Analysis specification |
Post-hoc
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.07 | ||||||||||||
Method |
Paired t-test | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collecter per study visit. One visit (visit 1) was before cholecystectomy and one visit (visit 2) was after cholecystectomy. At both visits a solid study meal with 1,250 mg chenodeoxycholic acid (IMP) was admisitered
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
2021-03-31
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Reporting groups
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Reporting group title |
Visit 1 (pre-operative visit)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Visit2 (post-operative visit)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
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 |