Safety and Efficacy Study of 2 Pancreatic Enzymes for Treatment of Exocrine Pancreatic Insufficiency in Cystic Fibrosis.

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.

Study Overview

• Status: Completed
• Conditions: Exocrine Pancreatic Insufficiency: Cystic Fibrosis
• Intervention / Treatment: Drug: EUR-1008 25,000 Units; Drug: Kreon 25,000 Units

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • University Hospital Antwerp - Universitair Ziekenhuis Antwerpen (UZA)
  • Gent, Belgium
    • Universitair Ziekenhuis Gent, Centrum voor Mucoviscidose
• Bulgaria
  • Pleven, Bulgaria
    • Clinic of Paediatric Diseases at UMHAT Dr Georgi Stranski
  • Plovdiv, Bulgaria
    • Clinic of Genetic and Paediatric Diseases at UMHAT Sveti Georgi
  • Ruse, Bulgaria
    • Specialized Hospital for Active Treatment of Pulmological and Phtisiatric Disease
  • Varna, Bulgaria
    • Multiprofile Clinic for Specialized Pediatric Clinic at MHAT Sveta Marina
• France
  • Montpellier Cedex 5, France
    • Hopital Arnaud de Villeneuve
  • Strasbourg Cedex, France
    • Nouvel Hôpital Civil
• Germany
  • Bochum, Germany
    • Ruhr-Universitaet Bochum - St. Josef Hospital
  • Dresden, Germany
    • Universitaetsklinikum Carl Gustav Carus an der TU Dresden
  • Essen, Germany
    • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitaetsklinikum Essen gGmbH
  • Essen, Germany
    • Universitätsklinikum Essen Zentrum f.Kinderheilkunde Klinik f.Kinderheilkunde III
  • Jena, Germany
    • Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin
  • Muenchen, Germany
    • Medizinische Klinik Innenstadt
  • Tuebingen, Germany
    • Universitaetsklinik für Kinder- und Jugendmedizin Tuebingen
• Italy
  • Ancona, Italy
    • Azienda Ospedaliero Universitaria, Ospedali Riuniti, Ospedale Pediatrico G. Salesi
  • Bari, Italy
    • Azienda Ospedale Policlinico di Bari
  • Catania, Italy
    • University of Catania
  • Contesse -Messina, Italy
    • Azienda Ospedaliera Universitaria Policlinico G. Martino, Gastroenterologia Pediatrica E Fibrosi Cistica
  • Naples, Italy
    • University Federico II of Naples, Pediatrics Department
  • Orbassano (Torino), Italy
    • Clinica di Malattie dell'Apparato Respiratorio
  • Parma, Italy
    • Istituto Azienda Ospedaliera Universitaria
  • Roma, Italy
    • Universita degli Studi di Roma La Sapienza, Azienda Policlinico Umberto I, Dipartimento di Pediatria, Centro Fibrosi Cistica Regione Lazio
  • Rome, Italy
    • Bambino Gesu Hospital, Cystic Fibrosis Unit
  • Turin, Italy
    • Ospedale Infantile Regina Margherita
  • Verona, Italy
    • Azienda Ospedaliera Universitaria Integrata, Centro Fibrosi Cistica-Ospedale Civile Maggiore
• Poland
  • Gdansk, Poland
    • Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem Poradnia Leczenia Mukowiscydozy
  • Karpacz, Poland
    • Centrum Pulmonologii i Alergologii w Karpaczu
  • Lodzi, Poland
    • Wojewodzki Szpital Specjalistyczny im Kopernika
  • Lublin, Poland
    • ALERGOTEST s.c Specjalistyczne Centrum Medyczne
  • Poznan, Poland
    • Szpital Kliniczny im Karola Jonschera
  • Rabka Zdrój, Poland
    • NZOZ Sanatorium Cassia Villa Medica
  • Rzeszow, Poland
    • NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
  • Warszawa, Poland
    • Centrum Zdrowia Matki, Dziecka i Mlodziezy
  • Warszawa, Poland
    • IRMED Irena Wojciechowska
• United Kingdom
  • Liverpool, United Kingdom
    • Liverpool Heart and Chest Hospital
  • Sheffield, United Kingdom
    • Sheffield Children's Hospital, The Academic Unit of Child Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Pancreatic insufficiency documented by a monoclonal faecal elastase (FE) 100 μg/g stool at screening (test results within the previous 12 months are acceptable)
3. Currently receiving pancreatic enzyme replacement therapy
4. 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
5. 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:

1. Age <12 years
2. Known contraindication, hypersensitivity, or intolerance to pork or other porcine PEPs
3. Current uncontrolled diabetes mellitus
4. History of solid organ transplantation
5. History of surgery affecting the bowel function and weight gain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EUR-1008 then Kreon; EUR-1008 during Treatment Period 1 (29 days ±2 days) and; Kreon during Treatment Period 2 (29 days ±2 days).	Drug: EUR-1008 25,000 Units; 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.; Other Names: Zenpep; Drug: Kreon 25,000 Units; 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.; Other Names: Kreon
Experimental: Kreon then EUR-1008; Kreon during Treatment Period 1 (29 days ±2 days) and; EUR-1008 during Treatment Period 2 (29 days ±2 days).	Drug: EUR-1008 25,000 Units; 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.; Other Names: Zenpep; Drug: Kreon 25,000 Units; 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.; Other Names: Kreon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Body weight at baseline (Visit 2 [Day 0]) and at the end of each treatment period.	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.	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)	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).	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).	58 days
Treatment Emergent Adverse Events	Frequency, duration, and severity of treatment-emergent adverse events (TEAEs);	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	58 days
Vital signs	Vital signs including blood pressure, heart rate, respirations and body temperature.	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).	58 days

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Principal Investigator: Christopher Taylor, MD, PhD, Sheffield Children's Hospital, The Academic Unit of Child Health

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 16, 2012

Study Record Updates

• Last Update Posted (Estimate): March 14, 2014
• Last Update Submitted That Met QC Criteria: March 13, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Pancreatic Insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: PR-005; 2009-012842-21 (EudraCT Number)