Clinical Trial Results:
An Open-Label, Multicenter, Randomized, Cross-over Study to Compare the Safety and Efficacy of Panzytrat® 25,000 to Kreon® 25,000 in the Control of Steatorrhea in Subjects Aged 7 Years and Older with Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (EPI)
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Summary
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EudraCT number |
2010-019267-11 |
Trial protocol |
DE |
Global end of trial date |
14 May 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Aug 2018
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First version publication date |
22 Aug 2018
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Other versions |
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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 |
MA-PA25CF10-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01327703 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Forest Laboratories, LLC, an Allergan Affiliate
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Sponsor organisation address |
5 Giralda Farms, Madison, United States, 07940
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Public contact |
Clinical Trials Registry Team, Allergan plc, 001 877‐277‐8566, IR-CTRegistration@allergan.com
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Scientific contact |
Therapeutic Area Head, Allergan plc, 001 862-261-7000, IR-CTRegistration@Allergan.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 May 2012
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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 |
14 May 2012
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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 |
This study assessed the efficacy and safety of Panzytrat® 25,000 compared to Kreon® 25,000 in the control of steatorrhea in participants with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI).
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Apr 2011
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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 |
Germany: 60
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Country: Number of subjects enrolled |
Poland: 27
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Worldwide total number of subjects |
87
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EEA total number of subjects |
87
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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) |
37
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Adolescents (12-17 years) |
35
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Adults (18-64 years) |
15
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at 14 investigative sites in Germany and Poland from 7 April 2011 to 14 May 2012. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Participants with a diagnosis of with Cystic Fibrosis and Exocrine Pancreatic Insufficiency where enrolled in this crossover study and received Panzytrat® 25,000 and Kreon® 25,000. | ||||||||||||||||||
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Period 1
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Period 1 title |
First Treatment Period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Panzytrat® First, Then Kreon® | ||||||||||||||||||
Arm description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 European Pharmacopoeia (Ph.Eur.) units lipase/kilogram (kg) body weight/day. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Panzytrat®
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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 |
≤10,000 Ph.Eur.-E. units lipase/kilogram(kg) body weight/day.
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Arm title
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Kreon® First, Then Panzytrat® | ||||||||||||||||||
Arm description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 Ph.Eur. units lipase/kg body weight/day. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Kreon®
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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 |
≤10,000 Ph.Eur.-E. units lipase/kilogram(kg) body weight/day.
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Period 2
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Period 2 title |
Second Treatment Period
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Panzytrat® First, Then Kreon® | ||||||||||||||||||
Arm description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 European Pharmacopoeia (Ph.Eur.) units lipase/kilogram (kg) body weight/day. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Kreon®
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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 |
≤10,000 Ph.Eur.-E. units lipase/kilogram(kg) body weight/day.
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Arm title
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Kreon® First, Then Panzytrat® | ||||||||||||||||||
Arm description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 Ph.Eur. units lipase/kg body weight/day. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Panzytrat®
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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 |
≤10,000 Ph.Eur.-E. units lipase/kilogram(kg) body weight/day.
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| Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 3 participants who completed Period 1 did not participate in Period 2. |
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Baseline characteristics reporting groups
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Reporting group title |
First Treatment Period
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Panzytrat® First, Then Kreon®
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Reporting group description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 European Pharmacopoeia (Ph.Eur.) units lipase/kilogram (kg) body weight/day. | ||
Reporting group title |
Kreon® First, Then Panzytrat®
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Reporting group description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 Ph.Eur. units lipase/kg body weight/day. | ||
Reporting group title |
Panzytrat® First, Then Kreon®
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Reporting group description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 European Pharmacopoeia (Ph.Eur.) units lipase/kilogram (kg) body weight/day. | ||
Reporting group title |
Kreon® First, Then Panzytrat®
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Reporting group description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 Ph.Eur. units lipase/kg body weight/day. | ||
Subject analysis set title |
Panzytrat®
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Kreon®
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Panzytrat®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Kreon®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Panzytrat®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Kreon®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Kreon®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Panzytrat®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Kreon®
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period.
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Subject analysis set title |
Kreon®, First, Then Panzytrat®
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in first treatment period followed by Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in second treatment period. Stabilized dose for a participant was the optimal dose determined during a qualification phase that preceded the first treatment period and was based upon the participant's usual lipase and lipid intake and total dose was not to exceed 10,000 Ph.Eur. units lipase/kg body weight/day.
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End point title |
Percent Coefficient of Fat Absorption (CFA) | ||||||||||||
End point description |
Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools which were collected over a 3-day period (Day 12 to morning of Day 15) during each treatment period. Least squares mean percent (%) CFA was calculated for Day 12 to Day 15 in first and second treatment periods. Percent CFA was based on log transformed data.
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End point type |
Primary
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End point timeframe |
Day 12 up to Day 15 in first and second treatment periods
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Mixed model analysis method was used for comparison using log-transformed percent CFA as the response variable, fixed effect factors for treatment, period, treatment sequence and pooled site and participant within treatment sequence as a random effect.
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Comparison groups |
Panzytrat® v Kreon®
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Number of subjects included in analysis |
76
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Analysis specification |
Pre-specified
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Analysis type |
[1] | ||||||||||||
P-value |
= 0.459 [2] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-2.08
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-7.23 | ||||||||||||
upper limit |
4.02 | ||||||||||||
| Notes [1] - Non-inferiority was declared if the lower bound of the 2-sided 95% confidence interval (CI) of Panzytrat® versus Kreon® exceeded -10%. [2] - As there was only a single pre-specified primary analysis, there was no adjustment for multiplicity. |
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End point title |
Mean Daily Number of Stools | ||||||||||||
End point description |
Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools during the collection period (Day 12 to Day 15 in first and second treatment periods) for total participants was summarized.
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End point type |
Secondary
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End point timeframe |
Day 12 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Stools With Normal Consistency | ||||||||||||
End point description |
Normal consistency of stool was defined as formed hard, normal or soft stool and abnormal consistency was defined as loose and unformed, liquid stool and diarrhea. Percentage of stools with normal consistency of each participant was calculated as the number of stools with normal consistency relative to the total number of stools during the collection period. Mean percentage of stool with normal consistency during the collection period (Day 12 to Day 15 in first and second treatment periods) for total participants was summarized.
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End point type |
Secondary
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End point timeframe |
Day 12 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Total Weight of Stools | ||||||||||||
End point description |
Mean total weight of stools was calculated for Day 12 to Day 15 in first and second treatment periods.
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End point type |
Secondary
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End point timeframe |
Day 12 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Weight per Stool Sample | ||||||||||||
End point description |
Mean weight per stool sample was calculated for Day 12 to Day 15 in first and second treatment periods.
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End point type |
Secondary
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End point timeframe |
Day 12 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Relative Frequency of Days With Abdominal Symptoms | ||||||||||||||||||||||||||||||||||||
End point description |
Abdominal symptoms included abdominal pain and flatulence. Symptoms were classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). For each type of abdominal symptom, the relative frequency of days with the symptom for each participant in a treatment period was calculated as the number of days in which the symptom was reported divided by the total number of days in which the abdominal symptom case report form (CRF) was completed. Mean relative frequency of days with abdominal symptoms was calculated during each treatment period (Day 1 to Day 15).
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Participants With Abdominal Distension | ||||||||||||
End point description |
Abdominal distension is a sense of increased abdominal pressure by the participant that involves an actual measurable change in the circumference of a participant’s abdomen on physical examination. Percentage of participants with abdominal distension was calculated for each treatment period (Day 1 to Day 15).
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Coefficient of Fat Absorption (CFA) Based on Concomitant use of Proton Pump Inhibitors (PPIs) | ||||||||||||||||||
End point description |
Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools which were collected over a 3-day period (Day 12 to morning of Day 15) during each treatment period. Least squares mean percent (%) CFA was calculated for Day 12 to Day 15 in first and second treatment periods. Percent CFA was based on log transformed data. Percent CFA was calculated separately for participants who used and did not use acid suppressing therapy (PPIs) during the study.
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End point type |
Secondary
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End point timeframe |
Day 12 up to Day 15 in first and second treatment periods
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | |||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence regardless of its causal relationship to study drug. A TEAE was defined as any event not present prior to exposure to study drug or any event already present that worsens in either intensity or frequency following exposure to test drug. A SAE was defined as any event that results in death, is immediately life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect or is assessed as medically important.
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End point type |
Secondary
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End point timeframe |
Baseline up to 30 days after last dose
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Nutritional Status as Assessed by Body Weight | ||||||||||||||||||
End point description |
Mean body weight was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
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End point type |
Secondary
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End point timeframe |
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Nutritional Status as Assessed by Body Mass Index (BMI) | ||||||||||||||||||
End point description |
Nutritional status of participants was assessed by determining their BMI. BMI was calculated by dividing body weight (kg) by square of height in meter (m). Mean BMI was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
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End point type |
Secondary
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End point timeframe |
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Nutritional Status as Assessed by Electrolytes Level [3] | ||||||||||||||||||||||||||||||
End point description |
Nutritional status of participants was assessed by determining their electrolytes (sodium, potassium and chloride) level. Mean electrolytes level was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
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End point type |
Secondary
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End point timeframe |
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: A Subject Analysis Set was used for the Kreon® First, Then Panzytrat® arm of the Baseline Period. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | ||||||||||||||||||||||||||||||
End point description |
Nutritional status of participants was assessed by determining their albumin, serum transferrin and hemoglobin level. Mean albumin, serum transferrin and hemoglobin level was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
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End point type |
Secondary
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End point timeframe |
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Nutritional Status as Assessed by Hematocrit Level | ||||||||||||||||||
End point description |
Nutritional status of participants was assessed by determining their hematocrit level. Mean hematocrit level was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
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End point type |
Secondary
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End point timeframe |
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
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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 |
Baseline up to 30 days after last dose
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Adverse event reporting additional description |
Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect. Participants at risk: Panzytrat®=86 and Kreon®=85.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
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Reporting groups
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Reporting group title |
Kreon®
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Reporting group description |
Kreon® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Panzytrat®
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Reporting group description |
Panzytrat® 25,000 capsule orally daily at a stabilized dose, as per investigator's discretion, for 14 days in either first treatment period or second treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Aug 2010 |
Amendment 1:
-Added “proposal of a new example of compliance calculation with a lower daily fixed dose of capsules (18 capsules per day was changed for 12 capsules per day)”;
-Inclusion criteria: added subject has a diagnosis of severe EPI confirmed by ELISA measurement of fecal elastase (FE-I) (test could have been performed in the past and result available);
-Inclusion criteria: added women of childbearing potential must have a negative pregnancy test at study entry and must use a medically acceptable contraceptive method for the duration of the study (i.e. from the qualification visit up to 30 days after the last study visit);
-Exclusion criteria: added recent treatment of an emergent acute infection with oral or intravenous (IV) antibiotics that was not stopped at least 14 days prior to randomization;
-Exclusion criteria: added use of enteral tube feeding over day and night;
-Qualification phase: added this phase will last 5 to 15 days in order to obtain FE-I result (if necessary) ... standardized Cystic Fibrosis (CF) diet and standardized dose of lipase;
-Prohibited medications: added chronic use of inhaled or oral antibiotics for infection prophylaxis is allowed provided that the drugs and the doses remain the same during the study;
-Added “females who do not use an acceptable contraceptive regimen will be allowed to participate in this study only if they are not of childbearing potential”;
-Added “subjects will only be identified with a subject identifier”; |
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06 Aug 2010 |
-Added the “study personnel will contact the subject by phone on Day 10 to remind him/her to start the accurate food recording on Day 11”;
-Added to Period 1: The subject will continue the same standardized diet and will continue the food recording very accurately from Day 12 to Day 15 AM. During this period, the subject will continue to record the number of capsules of study drug taken at each meal and snack and the presence of abdominal symptoms (abdominal pain and flatulence) as well;
-Added “stools will be kept refrigerated or frozen”;
-added “The physical exam will collect body weight in kilograms (kg), height in centimeters (cm) and vital signs after the subject has been seated for at least 5 minutes”;
-Added “study procedures will not resume before 14 days after the end of antibiotic administration and the maximal time frame for the PAUSE period will be 45 days”;
-Added “all samples of urine and blood will be sent to a local laboratory for analysis and all samples of stools will be sent to a central laboratory according to their shipment requirements. For sites that cannot have vitamins A, D and E analysis at their local laboratory, frozen serum will be sent to the central laboratory for analysis”;
-Added “The investigator has the responsibility to notify the local Ethics Committee about serious adverse events (SAEs) according to local regulatory requirements”. |
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24 Sep 2010 |
Amendment 2:
-Removed “Study Phase: IIIb” and replaced with “Study Phase: IV”, in all applicable areas. |
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05 Oct 2011 |
Amendment 3:
-Added “Axcan Pharma Inc. was replaced by Aptalis Pharma Canada, Inc, because on September 8, 2011, Axcon Pharma Inc., a subsidiary of Aptalis Pharma Inc., changed its name to Aptalis Pharma Canada. Inc.”; -Added “Axcon Pharma SAS was replaced by Apatalis Pharma SAS, because on June 8, 2011, Axcan Pharma SAS, a subsidiary of Aptalis Pharma Inc., changed its name to Aptalis SAS.”; -Added “capsules of lower dosage will not be allowed for snacks and small meals. The usual enzyme treatment capsules (Panzytrat® 25,000 or Kreon® 25,000) will need to be opened to provide a smaller amount of lipase”, to the study description; -Updated the list and contact information of the sponsor’s personnel involved in the study; -Removed the Netherlands from the list of countries with study sites involved in this study; -Exclusion criteria: Use of enteral tube feeding or gastric tube feeding (G-tube) for continuous feeding over day or night; -Clarified the dose will be limited to a maximum of 4000 lipase units per gram of fat ingested and will not exceed 10,000 The European Pharmacopoeia (Ph.Eur.-E) units of lipase per kilogram of body weight per day; -Clarified the primary efficacy endpoint – only fat intakes cumulated over Day 12, Day 13 and Day 14 will be used to calculate the CFA%%. |
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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 | |||
