Back to resultsSafety and Efficacy Study of 2 Pancreatic Enzymes for Treatment of Exocrine Pancreatic Insufficiency in Cystic Fibrosis.
Primary Purpose
Exocrine Pancreatic Insufficiency: Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
EUR-1008 25,000 Units
Kreon 25,000 Units
Sponsored by
About this trial
This is an interventional treatment trial for Exocrine Pancreatic Insufficiency: Cystic Fibrosis focused on measuring Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Pancreatic Insufficiency
Eligibility Criteria
Inclusion Criteria:
Definitive diagnosis of CF based on the following:
- One clinical feature consistent with CF and
- Either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration >60 mEq/L by pilocarpine iontophoresis
- Pancreatic insufficiency documented by a monoclonal faecal elastase (FE) 100 μg/g stool at screening (test results within the previous 12 months are acceptable)
- Currently receiving pancreatic enzyme replacement therapy
- Adequate nutritional status based on the following: body mass index (BMI) >19 kg/m2 in adult subjects or a BMI percentile 10th percentile for age in adolescent (12 to 17 years age group) subjects
- Are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection that requires antibiotics during the 7-day interval prior to screening and preceding entry into this clinical study
Exclusion Criteria:
- Age <12 years
- Known contraindication, hypersensitivity, or intolerance to pork or other porcine PEPs
- Current uncontrolled diabetes mellitus
- History of solid organ transplantation
- History of surgery affecting the bowel function and weight gain
Sites / Locations
- University Hospital Antwerp - Universitair Ziekenhuis Antwerpen (UZA)
- Universitair Ziekenhuis Gent, Centrum voor Mucoviscidose
- Clinic of Paediatric Diseases at UMHAT Dr Georgi Stranski
- Clinic of Genetic and Paediatric Diseases at UMHAT Sveti Georgi
- Specialized Hospital for Active Treatment of Pulmological and Phtisiatric Disease
- Multiprofile Clinic for Specialized Pediatric Clinic at MHAT Sveta Marina
- Hôpital Arnaud de Villeneuve
- Nouvel Hôpital Civil
- Ruhr-Universitaet Bochum - St. Josef Hospital
- Universitaetsklinikum Carl Gustav Carus an der TU Dresden
- Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitaetsklinikum Essen gGmbH
- Universitätsklinikum Essen Zentrum f.Kinderheilkunde Klinik f.Kinderheilkunde III
- Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
- Medizinische Klinik Innenstadt
- Universitaetsklinik für Kinder- und Jugendmedizin Tuebingen
- Azienda Ospedaliero Universitaria, Ospedali Riuniti, Ospedale Pediatrico G. Salesi
- Azienda Ospedale Policlinico di Bari
- University of Catania
- Azienda Ospedaliera Universitaria Policlinico G. Martino, Gastroenterologia Pediatrica E Fibrosi Cistica
- University Federico II of Naples, Pediatrics Department
- Clinica di Malattie dell'Apparato Respiratorio
- Istituto Azienda Ospedaliera Universitaria
- Universita degli Studi di Roma La Sapienza, Azienda Policlinico Umberto I, Dipartimento di Pediatria, Centro Fibrosi Cistica Regione Lazio
- Bambino Gesu Hospital, Cystic Fibrosis Unit
- Ospedale Infantile Regina Margherita
- Azienda Ospedaliera Universitaria Integrata, Centro Fibrosi Cistica-Ospedale Civile Maggiore
- Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem Poradnia Leczenia Mukowiscydozy
- Centrum Pulmonologii i Alergologii w Karpaczu
- Wojewodzki Szpital Specjalistyczny im Kopernika
- ALERGOTEST s.c Specjalistyczne Centrum Medyczne
- Szpital Kliniczny im Karola Jonschera
- NZOZ Sanatorium Cassia Villa Medica
- NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
- Centrum Zdrowia Matki, Dziecka i Mlodziezy
- IRMED Irena Wojciechowska
- Liverpool Heart and Chest Hospital
- Sheffield Children's Hospital, The Academic Unit of Child Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
EUR-1008 then Kreon
Kreon then EUR-1008
Arm Description
EUR-1008 during Treatment Period 1 (29 days ±2 days) and Kreon during Treatment Period 2 (29 days ±2 days).
Kreon during Treatment Period 1 (29 days ±2 days) and EUR-1008 during Treatment Period 2 (29 days ±2 days).
Outcomes
Primary Outcome Measures
Coefficient of Fat Absorption over 72 hours (CFA-72h)
During the last 72 hours of each treatment period, the CFA-72h will be calculated using fat intake data from the diet and fat excretion data from stools. Fat intake will be calculated by the dietician in collaboration with the study investigator using a validated tool.
Secondary Outcome Measures
Body weight
Body weight at baseline (Visit 2 [Day 0]) and at the end of each treatment period.
Coefficient of nitrogen absorption
Coefficient of nitrogen absorption at the end of each treatment period as assessed by a specialised central laboratory by means of Dumas combustion method.
Control of signs and symptoms of EPI
Control of signs and symptoms of EPI (as recorded in subject diaries). The following will be captured:
Stools frequency (number/day)
Stools consistency (hard, formed/normal; soft, watery, overt diarrhoea)
Fat or grease visible in stools (Yes/No)
Abdominal pain (mild, moderate, severe)
Bloating (mild, moderate, severe)
Flatulence (mild, moderate, severe)
Impact on overall health, daily life, perceived well-being, and symptoms
Impact on overall health, daily life, perceived well-being, and symptoms evaluated using the CFQ (administered by designated study personnel prior to randomisation and at the end of each treatment period).
Total cholesterol, calculated LDL-C, HDL-C
Total cholesterol, calculated LDL-C, HDL-C (sampling performed prior to randomisation and at the end of each treatment period).
Treatment Emergent Adverse Events
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs);
Standard safety laboratory tests
Standard safety laboratory tests, analysed by central laboratory:
Haematology: red blood cell count, haemoglobin, haematocrit, total leukocytes with diff count, and platelets
Serum biochemistry: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, total bilirubin, direct and indirect bilirubin, blood urea nitrogen, uric acid, creatinine, fasting plasma glucose, fasting cholesterol evaluations (total cholesterol, LDL-C, HDL-C, and triglycerides), fat-soluble vitamins (A, D, and E) and serum electrolytes
Vital signs
Vital signs including blood pressure, heart rate, respirations and body temperature.
Fat-soluble vitamins A, D, and E
Fat-soluble vitamins A, D, and E (sampling performed prior to randomisation and at the end of each treatment period).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01641393
Brief Title
Safety and Efficacy Study of 2 Pancreatic Enzymes for Treatment of Exocrine Pancreatic Insufficiency in Cystic Fibrosis.
Official Title
A Randomised, Double-Blind, Active-Controlled, Two-Treatment, Crossover, Multinational, Multicentre Study to Compare Two Pancreatic Enzyme Products in the Treatment of Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forest Laboratories
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to further evaluate the safety and efficacy of EUR-1008 as compared to Kreon® in the treatment of exocrine pancreatic insufficiency associated with Cystic Fibrosis in subjects 12 years of age and older.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Exocrine Pancreatic Insufficiency: Cystic Fibrosis
Keywords
Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Pancreatic Insufficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EUR-1008 then Kreon
Arm Type
Experimental
Arm Description
EUR-1008 during Treatment Period 1 (29 days ±2 days) and
Kreon during Treatment Period 2 (29 days ±2 days).
Arm Title
Kreon then EUR-1008
Arm Type
Experimental
Arm Description
Kreon during Treatment Period 1 (29 days ±2 days) and
EUR-1008 during Treatment Period 2 (29 days ±2 days).
Intervention Type
Drug
Intervention Name(s)
EUR-1008 25,000 Units
Other Intervention Name(s)
Zenpep
Intervention Description
EUR-1008 25,000 Units is a PEP with pancreas powder as the active ingredient.18 Pancreas powder contains various enzymes having proteolytic, lipolytic, and amylolytic activity. Each capsule contains approximately 25,000 Ph. Eur. lipase units. EUR-1008 25,000 consists of orally administered capsules containing enteric-coated beads.
Intervention Type
Drug
Intervention Name(s)
Kreon 25,000 Units
Other Intervention Name(s)
Kreon
Intervention Description
Kreon 25,000 is a PEP consisting of porcine-derived pancreatic enzymes.18 Each capsule contains approximately 25,000 Ph. Eur. lipase units. Kreon 25,000 consists of orally administered capsules containing enteric-coated spheres.
Primary Outcome Measure Information:
Title
Coefficient of Fat Absorption over 72 hours (CFA-72h)
Description
During the last 72 hours of each treatment period, the CFA-72h will be calculated using fat intake data from the diet and fat excretion data from stools. Fat intake will be calculated by the dietician in collaboration with the study investigator using a validated tool.
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Body weight
Description
Body weight at baseline (Visit 2 [Day 0]) and at the end of each treatment period.
Time Frame
58 days.
Title
Coefficient of nitrogen absorption
Description
Coefficient of nitrogen absorption at the end of each treatment period as assessed by a specialised central laboratory by means of Dumas combustion method.
Time Frame
72 hours
Title
Control of signs and symptoms of EPI
Description
Control of signs and symptoms of EPI (as recorded in subject diaries). The following will be captured:
Stools frequency (number/day)
Stools consistency (hard, formed/normal; soft, watery, overt diarrhoea)
Fat or grease visible in stools (Yes/No)
Abdominal pain (mild, moderate, severe)
Bloating (mild, moderate, severe)
Flatulence (mild, moderate, severe)
Time Frame
2- 14 day periods
Title
Impact on overall health, daily life, perceived well-being, and symptoms
Description
Impact on overall health, daily life, perceived well-being, and symptoms evaluated using the CFQ (administered by designated study personnel prior to randomisation and at the end of each treatment period).
Time Frame
58 days
Title
Total cholesterol, calculated LDL-C, HDL-C
Description
Total cholesterol, calculated LDL-C, HDL-C (sampling performed prior to randomisation and at the end of each treatment period).
Time Frame
58 days
Title
Treatment Emergent Adverse Events
Description
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs);
Time Frame
78 days
Title
Standard safety laboratory tests
Description
Standard safety laboratory tests, analysed by central laboratory:
Haematology: red blood cell count, haemoglobin, haematocrit, total leukocytes with diff count, and platelets
Serum biochemistry: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, total bilirubin, direct and indirect bilirubin, blood urea nitrogen, uric acid, creatinine, fasting plasma glucose, fasting cholesterol evaluations (total cholesterol, LDL-C, HDL-C, and triglycerides), fat-soluble vitamins (A, D, and E) and serum electrolytes
Time Frame
58 days
Title
Vital signs
Description
Vital signs including blood pressure, heart rate, respirations and body temperature.
Time Frame
78 days
Title
Fat-soluble vitamins A, D, and E
Description
Fat-soluble vitamins A, D, and E (sampling performed prior to randomisation and at the end of each treatment period).
Time Frame
58 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Definitive diagnosis of CF based on the following:
One clinical feature consistent with CF and
Either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration >60 mEq/L by pilocarpine iontophoresis
Pancreatic insufficiency documented by a monoclonal faecal elastase (FE) 100 μg/g stool at screening (test results within the previous 12 months are acceptable)
Currently receiving pancreatic enzyme replacement therapy
Adequate nutritional status based on the following: body mass index (BMI) >19 kg/m2 in adult subjects or a BMI percentile 10th percentile for age in adolescent (12 to 17 years age group) subjects
Are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection that requires antibiotics during the 7-day interval prior to screening and preceding entry into this clinical study
Exclusion Criteria:
Age <12 years
Known contraindication, hypersensitivity, or intolerance to pork or other porcine PEPs
Current uncontrolled diabetes mellitus
History of solid organ transplantation
History of surgery affecting the bowel function and weight gain
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Taylor, MD, PhD
Organizational Affiliation
Sheffield Children's Hospital, The Academic Unit of Child Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Antwerp - Universitair Ziekenhuis Antwerpen (UZA)
City
Antwerp
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent, Centrum voor Mucoviscidose
City
Gent
Country
Belgium
Facility Name
Clinic of Paediatric Diseases at UMHAT Dr Georgi Stranski
City
Pleven
Country
Bulgaria
Facility Name
Clinic of Genetic and Paediatric Diseases at UMHAT Sveti Georgi
City
Plovdiv
Country
Bulgaria
Facility Name
Specialized Hospital for Active Treatment of Pulmological and Phtisiatric Disease
City
Ruse
Country
Bulgaria
Facility Name
Multiprofile Clinic for Specialized Pediatric Clinic at MHAT Sveta Marina
City
Varna
Country
Bulgaria
Facility Name
Hôpital Arnaud de Villeneuve
City
Montpellier Cedex 5
Country
France
Facility Name
Nouvel Hôpital Civil
City
Strasbourg Cedex
Country
France
Facility Name
Ruhr-Universitaet Bochum - St. Josef Hospital
City
Bochum
Country
Germany
Facility Name
Universitaetsklinikum Carl Gustav Carus an der TU Dresden
City
Dresden
Country
Germany
Facility Name
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitaetsklinikum Essen gGmbH
City
Essen
Country
Germany
Facility Name
Universitätsklinikum Essen Zentrum f.Kinderheilkunde Klinik f.Kinderheilkunde III
City
Essen
Country
Germany
Facility Name
Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
City
Jena
Country
Germany
Facility Name
Medizinische Klinik Innenstadt
City
Muenchen
Country
Germany
Facility Name
Universitaetsklinik für Kinder- und Jugendmedizin Tuebingen
City
Tuebingen
Country
Germany
Facility Name
Azienda Ospedaliero Universitaria, Ospedali Riuniti, Ospedale Pediatrico G. Salesi
City
Ancona
Country
Italy
Facility Name
Azienda Ospedale Policlinico di Bari
City
Bari
Country
Italy
Facility Name
University of Catania
City
Catania
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico G. Martino, Gastroenterologia Pediatrica E Fibrosi Cistica
City
Contesse -Messina
Country
Italy
Facility Name
University Federico II of Naples, Pediatrics Department
City
Naples
Country
Italy
Facility Name
Clinica di Malattie dell'Apparato Respiratorio
City
Orbassano (Torino)
Country
Italy
Facility Name
Istituto Azienda Ospedaliera Universitaria
City
Parma
Country
Italy
Facility Name
Universita degli Studi di Roma La Sapienza, Azienda Policlinico Umberto I, Dipartimento di Pediatria, Centro Fibrosi Cistica Regione Lazio
City
Roma
Country
Italy
Facility Name
Bambino Gesu Hospital, Cystic Fibrosis Unit
City
Rome
Country
Italy
Facility Name
Ospedale Infantile Regina Margherita
City
Turin
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Integrata, Centro Fibrosi Cistica-Ospedale Civile Maggiore
City
Verona
Country
Italy
Facility Name
Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem Poradnia Leczenia Mukowiscydozy
City
Gdansk
Country
Poland
Facility Name
Centrum Pulmonologii i Alergologii w Karpaczu
City
Karpacz
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny im Kopernika
City
Lodzi
Country
Poland
Facility Name
ALERGOTEST s.c Specjalistyczne Centrum Medyczne
City
Lublin
Country
Poland
Facility Name
Szpital Kliniczny im Karola Jonschera
City
Poznan
Country
Poland
Facility Name
NZOZ Sanatorium Cassia Villa Medica
City
Rabka Zdrój
Country
Poland
Facility Name
NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
City
Rzeszow
Country
Poland
Facility Name
Centrum Zdrowia Matki, Dziecka i Mlodziezy
City
Warszawa
Country
Poland
Facility Name
IRMED Irena Wojciechowska
City
Warszawa
Country
Poland
Facility Name
Liverpool Heart and Chest Hospital
City
Liverpool
Country
United Kingdom
Facility Name
Sheffield Children's Hospital, The Academic Unit of Child Health
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32761612
Citation
Somaraju URR, Solis-Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2020 Aug 5;8(8):CD008227. doi: 10.1002/14651858.CD008227.pub4.
Results Reference
derived
PubMed Identifier
27013382
Citation
Taylor CJ, Thieroff-Ekerdt R, Shiff S, Magnus L, Fleming R, Gommoll C. Comparison of two pancreatic enzyme products for exocrine insufficiency in patients with cystic fibrosis. J Cyst Fibros. 2016 Sep;15(5):675-80. doi: 10.1016/j.jcf.2016.02.010. Epub 2016 Mar 21.
Results Reference
derived
Learn more about this trial
Safety and Efficacy Study of 2 Pancreatic Enzymes for Treatment of Exocrine Pancreatic Insufficiency in Cystic Fibrosis.
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