Exocrine Pancreatic Insufficiency: Cystic FibrosisPhase 3NCT01641393
Safety and Efficacy Study of 2 Pancreatic Enzymes for Treatment of Exocrine Pancreatic Insufficiency in Cystic Fibrosis.
A Phase 3 study testing EUR-1008 25,000 Units and Kreon 25,000 Units in people with Exocrine Pancreatic Insufficiency: Cystic Fibrosis, run by Forest Laboratories at 37 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Exocrine Pancreatic Insufficiency: Cystic Fibrosis
- What is being tested?
- EUR-1008 25,000 Units and Kreon 25,000 Units
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 37 sitesin 7 countries
- Study dates
- Jun 2012to Feb 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
37 sites in 7 countries.
37 sites in 7 countries
Italy11 sites
Azienda Ospedaliero Universitaria, Ospedali Riuniti, Ospedale Pediatrico G. Salesi
Ancona
Azienda Ospedale Policlinico di Bari
Bari
University of Catania
Catania
Azienda Ospedaliera Universitaria Policlinico G. Martino, Gastroenterologia Pediatrica E Fibrosi Cistica
Contesse -Messina
University Federico II of Naples, Pediatrics Department
Naples
Clinica di Malattie dell'Apparato Respiratorio
Orbassano (Torino)
Istituto Azienda Ospedaliera Universitaria
Parma
Universita degli Studi di Roma La Sapienza, Azienda Policlinico Umberto I, Dipartimento di Pediatria, Centro Fibrosi Cistica Regione Lazio
Roma
Bambino Gesu Hospital, Cystic Fibrosis Unit
Rome
Ospedale Infantile Regina Margherita
Turin
Azienda Ospedaliera Universitaria Integrata, Centro Fibrosi Cistica-Ospedale Civile Maggiore
Verona
Poland9 sites
Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem Poradnia Leczenia Mukowiscydozy
Gdansk
Centrum Pulmonologii i Alergologii w Karpaczu
Karpacz
Wojewodzki Szpital Specjalistyczny im Kopernika
Lodz
ALERGOTEST s.c Specjalistyczne Centrum Medyczne
Lublin
Szpital Kliniczny im Karola Jonschera
Poznan
NZOZ Sanatorium Cassia Villa Medica
Rabka-Zdrój
NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
Rzeszów
Centrum Zdrowia Matki, Dziecka i Mlodziezy
Warsaw
IRMED Irena Wojciechowska
Warsaw
Germany7 sites
Ruhr-Universitaet Bochum - St. Josef Hospital
Bochum
Universitaetsklinikum Carl Gustav Carus an der TU Dresden
Dresden
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitaetsklinikum Essen gGmbH
Essen
Universitätsklinikum Essen Zentrum f.Kinderheilkunde Klinik f.Kinderheilkunde III
Essen
Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
Jena
Medizinische Klinik Innenstadt
München
Universitaetsklinik für Kinder- und Jugendmedizin Tuebingen
Tübingen
Bulgaria4 sites
Clinic of Paediatric Diseases at UMHAT Dr Georgi Stranski
Pleven
Clinic of Genetic and Paediatric Diseases at UMHAT Sveti Georgi
Plovdiv
Specialized Hospital for Active Treatment of Pulmological and Phtisiatric Disease
Rousse
Multiprofile Clinic for Specialized Pediatric Clinic at MHAT Sveta Marina
Varna
Belgium2 sites
University Hospital Antwerp - Universitair Ziekenhuis Antwerpen (UZA)
Antwerp
Universitair Ziekenhuis Gent, Centrum voor Mucoviscidose
Ghent
France2 sites
Hôpital Arnaud de Villeneuve
Montpellier
Nouvel Hôpital Civil
Strasbourg
United Kingdom2 sites
Liverpool Heart and Chest Hospital
Liverpool
Sheffield Children's Hospital, The Academic Unit of Child Health
Sheffield
About this study
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
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.
- Being tested
- EUR-1008 25,000 Units, Kreon 25,000 Units
- Keywords
- Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Pancreatic Insufficiency
- Medical subject headings
- Exocrine Pancreatic Insufficiency, Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EUR-1008 25,000 UnitsDrug
Also called Zenpep
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.
Kreon 25,000 UnitsDrug
Also called Kreon
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.
| Study group | Role | What they receive |
|---|---|---|
| EUR-1008 then Kreon | Experimental | * EUR-1008 during Treatment Period 1 (29 days ±2 days) and
* Kreon during Treatment Period 2 (29 days ±2 days). Receives: Drug: EUR-1008 25,000 Units; Drug: Kreon 25,000 Units |
| Kreon then EUR-1008 | Experimental | * Kreon during Treatment Period 1 (29 days ±2 days) and
* EUR-1008 during Treatment Period 2 (29 days ±2 days). Receives: Drug: EUR-1008 25,000 Units; Drug: Kreon 25,000 Units |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 72 hours
Secondary outcomes (9)
Body weight
Body weight at baseline (Visit 2 [Day 0]) and at the end of each treatment period.
Measured: 58 days.
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.
Measured: 72 hours
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)
Measured: 2- 14 day periods
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).
Measured: 58 days
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).
Measured: 58 days
Treatment Emergent Adverse Events
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs);
Measured: 78 days
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
Measured: 58 days
Vital signs
Vital signs including blood pressure, heart rate, respirations and body temperature.
Measured: 78 days
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).
Measured: 58 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2012 (estimated)
- Study startJun 2012
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Exocrine Pancreatic Insufficiency: Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Forest Laboratories
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christopher Taylor, MD, PhD, Principal investigator, Sheffield Children's Hospital, The Academic Unit of Child Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01641393
- Sponsor's protocol ID
- PR-005
- Other IDs
- 2009-012842-21, 2009
- Status last verified
- Mar 2014
- First submitted
- 10 Jul 2012
- Last updated
- 14 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32761612Taylor 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.
PubMed 27013382
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01641393
- Acronym / sponsor ID
- PR-005
- Keywords
- Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Pancreatic Insufficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Forest LaboratoriesIndustry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 16 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EUR-1008 then Kreon | Experimental | Drug: EUR-1008 25,000 Units, Drug: Kreon 25,000 Units* EUR-1008 during Treatment Period 1 (29 days ±2 days) and * Kreon during Treatment Period 2 (29 days ±2 days). |
| Kreon then EUR-1008 | Experimental | Drug: EUR-1008 25,000 Units, Drug: Kreon 25,000 Units* Kreon during Treatment Period 1 (29 days ±2 days) and * EUR-1008 during Treatment Period 2 (29 days ±2 days). |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Definitive diagnosis of CF based on the following:
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EUR-1008 25,000 UnitsAlso: ZenpepEUR-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. | Drug | EUR-1008 then Kreon, Kreon then EUR-1008 |
| Kreon 25,000 UnitsAlso: KreonKreon 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. | Drug | EUR-1008 then Kreon, Kreon then EUR-1008 |
Primary outcome
Coefficient of Fat Absorption over 72 hours (CFA-72h)
Time frame: 72 hours
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.
9 secondary outcomes
Body weight
Time frame: 58 days.
Coefficient of nitrogen absorption
Time frame: 72 hours
Control of signs and symptoms of EPI
Time frame: 2- 14 day periods
Impact on overall health, daily life, perceived well-being, and symptoms
Time frame: 58 days
Total cholesterol, calculated LDL-C, HDL-C
Time frame: 58 days
Treatment Emergent Adverse Events
Time frame: 78 days
Standard safety laboratory tests
Time frame: 58 days
Vital signs
Time frame: 78 days
Fat-soluble vitamins A, D, and E
Time frame: 58 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2014.
- Derived from this study: PubMed 32761612Somaraju 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.
- Derived from this study: PubMed 27013382Taylor 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Taylor, MD, PhD principal investigator
Sheffield Children's Hospital, The Academic Unit of Child Health
37 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing EUR-1008 25,000 Units and Kreon 25,000 Units in people with Exocrine Pancreatic Insufficiency: Cystic Fibrosis, run by Forest Laboratories at 37 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in Italy, Poland, Germany, Bulgaria, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Coefficient of Fat Absorption over 72 hours (CFA-72h) (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01641393, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2014.