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A Study to Investigate the Effect of Delayed Release Pancrelipase on Maldigestion in Patients With Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis and Pancreatectomy

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ClinicalTrials.gov Identifier: NCT00414908
Recruitment Status : Completed
First Posted : December 22, 2006
Results First Posted : September 16, 2009
Last Update Posted : August 10, 2011
Sponsor:
Information provided by:
Solvay Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Chronic Pancreatitis
Pancreatectomy
Pancreatic Exocrine Insufficiency
Interventions Drug: Pancrelipase delayed release capsule
Drug: Placebo Comparator
Enrollment 52
Recruitment Details Subjects were recruited in centers in Bulgaria, Poland, Russia, Serbia, Ukraine and US between April 2007 and August 2008. This report presents the double-blind (DB) period of the study as well as the Open Label (OL) results.
Pre-assignment Details There was a run-in with a 5-day of single-blind placebo treatment. One hundred and eighty subjects were consented and 179 entered the run-in. A total of 54 subjects were randomly allocated to treatment. Only two subjects did not complete the DB period of the treatment because of protocol violation. Fifty one patients entered the OL period.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description Pancrelipase delayed release capsules given during the Double-Blind period Placebo group given during the Double-Blind period
Period Title: Overall Study
Started 25 29
Completed 24 28
Not Completed 1 1
Reason Not Completed
Protocol Violation             1             1
Arm/Group Title Pancrelipase (DB) Placebo (DB) Total
Hide Arm/Group Description Pancrelipase delayed release capsules given during the Double-Blind period Placebo group given during the Double-Blind period Total of all reporting groups
Overall Number of Baseline Participants 24 28 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 28 participants 52 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
23
  95.8%
27
  96.4%
50
  96.2%
>=65 years
1
   4.2%
1
   3.6%
2
   3.8%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 28 participants 52 participants
51.7  (9.7) 50.4  (7.8) 51.0  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 28 participants 52 participants
Female
6
  25.0%
9
  32.1%
15
  28.8%
Male
18
  75.0%
19
  67.9%
37
  71.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 28 participants 52 participants
Serbia 1 3 4
United States 6 6 12
Poland 7 7 14
Ukraine 3 4 7
Russian Federation 2 2 4
Bulgaria 5 6 11
1.Primary Outcome
Title Change of Coefficient of Fat Absorption (CFA) (%) Between Baseline and End of Double-blind (DB) Period.
Hide Description

The CFA is calculated from fat intake and fat excretion : 100*[fat intake-fat excretion]/fat intake. Higher values indicated a better response.

Change is calculated as (DB CFA-Baseline CFA).

Time Frame End of double-blind period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 22 27
Mean (Standard Deviation)
Unit of Measure: Percentage
31.93  (18.57) 8.72  (12.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pancrelipase (DB), Placebo (DB)
Comments The following null hypothesis was tested (μ0 and μ1 denote the treatment group means respectively in the placebo and pancrelipase delayed release capsules group): H0: μ0 = μ1 (i.e., placebo and pancrelipase delayed release capsules are equal). The hypothesis corresponded to the primary objective to show superior efficacy of pancrelipase delayed release capsules over placebo. A non-parametric ANCOVA was used because the necessary assumptions were not met for the parametric ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Non parametric ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Change of Coefficient of Nitrogen Absorption (CNA) (%) Between Baseline and End of Double-blind (DB) Period.
Hide Description The CNA is calculated from nitrogen intake and nitrogen excretion : 100*[nitrogen intake-nitrogen excretion]/nitrogen intake. Higher values indicated a better response. Change is calculated as (DB CNA-Baseline CNA).
Time Frame End of double-blind period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 22 27
Mean (Standard Deviation)
Unit of Measure: Percentage
35.23  (29.05) 8.85  (28.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pancrelipase (DB), Placebo (DB)
Comments The following null hypothesis was tested (μ0 and μ1 denote the treatment group means respectively in the placebo and pancrelipase delayed release capsules group): H0: μ0 = μ1 (i.e., placebo and pancrelipase delayed release capsules are equal). The hypothesis corresponded to the primary objective to show superior efficacy of pancrelipase delayed release capsules over placebo. A non-parametric ANCOVA was used because the necessary assumptions were not met for the parametric ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Non parametric ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline of Stool Fat (g) Between Baseline and End of Double-blind (DB) Period.
Hide Description Total amount of fat excreted during the stool collection period. Lower values indicate a better response. Change was calculated as (DB Stool fat - Baseline stool fat).
Time Frame End of double-blind period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 22 27
Least Squares Mean (Standard Error)
Unit of Measure: Grammes
-147.08  (12.71) -34.62  (11.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pancrelipase (DB), Placebo (DB)
Comments

The following null hypothesis was tested (μ0 and μ1 denote the treatment group means in the placebo and pancrelipase delayed release capsules group): H0: μ0 = μ1 (i.e., placebo and pancrelipase capsules are equal).

The hypothesis was to show superior efficacy of pancrelipase delayed release capsules over placebo.

For this secondary efficacy variable, an analysis of covariance (ANCOVA) model was assumed with the treatment group as a fixed factor and the Stool fat at baseline as a covariate.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means difference
Estimated Value -112.45
Confidence Interval 95%
-147.04 to -77.87
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline of Stool Nitrogen (g) Between Baseline and End of Double-blind (DB) Period.
Hide Description Total amount of nitrogen excreted during the stool collection period. Lower values indicate a better response. Change was calculated as (DB Stool nitrogen - Baseline stool nitrogen).
Time Frame End of double-period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 22 27
Least Squares Mean (Standard Error)
Unit of Measure: Grammes
-17.55  (2.06) -5.87  (1.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pancrelipase (DB), Placebo (DB)
Comments

The following null hypothesis was tested (μ0 and μ1 denote the treatment group means in the placebo and pancrelipase delayed release capsules group): H0: μ0 = μ1 (i.e., placebo and pancrelipase capsules are equal).

The hypothesis was to show superior efficacy of pancrelipase delayed release capsules over placebo. For this secondary efficacy variable, an analysis of covariance (ANCOVA) model was assumed with the treatment group as a fixed factor and the Stool nitrogen at baseline as a covariate.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means difference
Estimated Value -11.68
Confidence Interval 95%
-17.30 to -6.06
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change of Stool Frequency Between Baseline and End of Double-blind (DB) Period
Hide Description Stool frequency is the average of the daily number of stools recorded during the treatment period. Lower values indicate a better response. Change was calculated as (DB stool frequency - Baseline Stool frequency).
Time Frame End of double-period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 23 28
Least Squares Mean (Standard Error)
Unit of Measure: Number
-0.55  (0.19) 0.20  (0.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pancrelipase (DB), Placebo (DB)
Comments

The following null hypothesis was tested (μ0 and μ1 denote the treatment group means in the placebo and pancrelipase delayed release capsules group): H0: μ0 = μ1 (i.e., placebo and pancrelipase capsules are equal). The hypothesis was to show superior efficacy of pancrelipase capsules over placebo.

For this secondary efficacy variable, an analysis of covariance (ANCOVA) model was assumed with the treatment group as a fixed factor and the Stool frequency at baseline as a covariate.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means difference
Estimated Value -0.76
Confidence Interval 95%
-1.27 to -0.24
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Abdominal Pain at the End of the Double-blind Period.
Hide Description 4- point ordinal scale on this symptom from 0 (No Abdominal pain) to 3 (Severe abdominal pain).
Time Frame End of double-period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 23 28
Measure Type: Number
Unit of Measure: Participants
0 (None) 12 8
1 (Mild) 7 12
2 (Moderate) 4 7
3 (Severe) 0 1
7.Secondary Outcome
Title Stool Consistency at the End of the Double-blind Period
Hide Description 4- point ordinal scale on this symptom from 0 (Hard) to 3 (Watery).
Time Frame End of double-period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 23 28
Measure Type: Number
Unit of Measure: Participants
0 (Hard) 0 0
1 (Formed/Normal) 11 5
2 (Soft) 12 20
3 (Watery) 0 3
8.Secondary Outcome
Title Flatulence at the End of Double-blind Period
Hide Description 4- point ordinal scale on this symptom from 0 (None) to 3 (Severe).
Time Frame End of double-period (5-7 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the Full Analysis sample. Full Analysis Population consists of all subjects who were allocated to the treatment and had data for at least one post-baseline assessment of any efficacy measurement.
Arm/Group Title Pancrelipase (DB) Placebo (DB)
Hide Arm/Group Description:
Pancrelipase delayed release capsules given during the Double-Blind period
Placebo group given during the Double-Blind period
Overall Number of Participants Analyzed 23 28
Measure Type: Number
Unit of Measure: Participants
0 (None) 6 0
1 (Mild) 13 15
2 (Moderate) 4 12
3 (Severe) 0 1
9.Other Pre-specified Outcome
Title Change of Stool Frequency Between "Original" Baseline and End of Open-label Period (OL)
Hide Description Stool frequency is the average of the daily number of stools recorded during the OL period. Lower values indicate a better response. Change was calculated as (OL stool frequency - Baseline stool frequency).
Time Frame 27 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis is done on the Open-Label period of 6 months.
Arm/Group Title Pancrelipase (OL)
Hide Arm/Group Description:
Pancrelipase delayed during Open-label. Dosing is directed by the investigator.
Overall Number of Participants Analyzed 47
Mean (Standard Deviation)
Unit of Measure: Number
-0.98  (1.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pancrelipase (OL)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Paired t-test
Comments Mean difference based on all subjects combined using the paired t-test between baseline and visit 8 or early termination
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pancrelipase (DB) Placebo (DB) Pancrelipase (OL)
Hide Arm/Group Description Pancrelipase delayed release capsules meaning the treatment received during the 7-days double-blind period Placebo group meaning the treatment received during the 7-days double-blind period Pancrelipase delayed capsules received by the patients during the 6-month Open Label. The dosing was directed by the investigator.
All-Cause Mortality
Pancrelipase (DB) Placebo (DB) Pancrelipase (OL)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pancrelipase (DB) Placebo (DB) Pancrelipase (OL)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/28 (0.00%)   7/51 (13.73%) 
Gastrointestinal disorders       
Acute and Chronic Pancreatitis * 1  0/24 (0.00%)  0/28 (0.00%)  1/51 (1.96%) 
Injury, poisoning and procedural complications       
Lower Limb Fractures and dislocations * 1  0/24 (0.00%)  0/28 (0.00%)  1/51 (1.96%) 
Thermal Burns * 1  0/24 (0.00%)  0/28 (0.00%)  1/51 (1.96%) 
Metabolism and nutrition disorders       
Diabetes Mellitus (Incl Subtypes) * 1  0/24 (0.00%)  0/28 (0.00%)  2/51 (3.92%) 
Diabetic Complication Dermal * 1  0/24 (0.00%)  0/28 (0.00%)  1/51 (1.96%) 
Respiratory, thoracic and mediastinal disorders       
Parenchymal Lung Disorders NEC * 1  0/24 (0.00%)  0/28 (0.00%)  1/51 (1.96%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pancrelipase (DB) Placebo (DB) Pancrelipase (OL)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/24 (4.17%)   2/28 (7.14%)   4/51 (7.84%) 
Infections and infestations       
Upper respiratory Tract infections * 1  0/24 (0.00%)  0/28 (0.00%)  4/51 (7.84%) 
Metabolism and nutrition disorders       
Hyperglycaemic conditions NEC * 1  1/24 (4.17%)  2/28 (7.14%)  0/51 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.1)
Only treatment emergent events have been presented. They are defined as events started at or after the 1st administration of study medication and includes events started prior to the 1st administration but which worsened after the 1st intake.
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.
At 60 days prior to submitting or presenting a manuscript or other materials relating to the Study to a publisher, reviewer, or other outside persons, the Site shall provide to Sponsor a copy and allow Sponsor 60 days to review and comment.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sven Voet - Global Communication
Organization: Abbott Products
Phone: +41 61 487 08 56
EMail: sven.voet@abbott.com
Layout table for additonal information
Responsible Party: Gregor Eibes, Solvay Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00414908     History of Changes
Other Study ID Numbers: S245.3.124
2004-000227-15 ( EudraCT Number )
First Submitted: December 21, 2006
First Posted: December 22, 2006
Results First Submitted: August 7, 2009
Results First Posted: September 16, 2009
Last Update Posted: August 10, 2011