Randomized Double-Blind Placebo Crossover Study to Evaluate Safety/Efficacy of Two Doses in CP Patients With EPI - Full Text View

Sponsored by:	Eurand S.p.A.
Information provided by:	Eurand S.p.A.
ClinicalTrials.gov Identifier:	NCT00788593

Purpose

The primary efficacy objective of the study is to evaluate the difference in Coefficient of Fat Absorption (CFA) of patients treated with high dose EUR-1008 vs. low dose of EUR-1008 in the treatment of signs and symptoms and management of malabsorption in patients with EPI associated with diagnosed Chronic Pancreatitis.

Condition	Intervention	Phase
Chronic Pancreatitis Exocrine Pancreatic Insufficiency	Drug: Placebo Drug: EUR-1008 high dose Drug: EUR-1008 low dose	Phase III

Drug Information available for: Lipase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 in Chronic Pancreatitis (CP) Patients With Exocrine Pancreatic Insufficiency (EPI)

Further study details as provided by Eurand S.p.A.:

Primary Outcome Measures:

The primary analysis conducted on all patients who complete both the high dose and low dose. An additional analysis will be conducted to calculate the difference between the mean CFA after administration of doses after administration. [ Time Frame: 78 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Calculation of the differences in CFA of patients on high dose EUR-1008 vs. CFA at placebo baseline and patients on low dose EUR-1008 vs. CFA at placebo baseline. Change in the CNA from baseline. Change in weight and BMI from baseline [ Time Frame: 78 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	78
Study Start Date:	January 2008
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Placebo: 7 capsules/day.	Drug: Placebo Placebo: 7 capsules/day each patient placebo is a four day home treatment followed by a 3-5 day hospitalization with 72-hour stool collection and controlled diet
2: Active Comparator EUR-1008 high dose: 140,000 lipase USP Lipase Units/day (7 x 20,000 USP Lipase Units capsules)	Drug: EUR-1008 high dose EUR-1008 high dose: 140,000 lipase USP Lipase Units/day (7 x 20,000 USP Lipase Units capsules)for six days dosage home treatment and 3-5 days hospital.
3: Active Comparator EUR-1008 low dose: 35,000 lipase USP Lipase Units/day (7 x 5,000 USP Lipase Units capsules )	Drug: EUR-1008 low dose EUR-1008 low dose: 35,000 lipase USP Lipase Units/day (7 x 5,000 USP Lipase Units capsules)for six days dosage home treatment and 3-5 days hospital.

Detailed Description:

After screening, eligible patients will start the placebo baseline ambulatory phase (4 days). On day 5, they will be hospitalized for three to five days, to undergo a "baseline" 72-hour CFA determination under a controlled diet and using a stool marker to indicate the beginning and end of the controlled diet period, while they continue receiving placebo treatment. At the end of the placebo baseline phase, patients will be randomized to a "high dose followed by a low dose" or to a "low dose followed by a high dose" EUR-1008 dose sequence and proceed to the first crossover phase. Each crossover phase will consist of a stabilization period for six days at home, followed by a hospitalization of three to five days to undergo a 72-hour CFA determination using a controlled diet and using a stool marker to indicate the beginning and end of the controlled diet period.

Patients will proceed from the first to the second randomized crossover phase without a washout or return-to-baseline period in between phases. Patients will be stabilized at home for 6 days. Any residual lipase from the prior treatment phase is likely to be a negligible influence on the subsequent CFA determination because patients will be taking the new dose level (high or low) for six days before the beginning of sample collection for a new CFA. This interval is more than enough time for the CFA to be reflective of only the new dose.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female
Age over 18
Written, legally valid informed consent
Women of childbearing potential must be using a medically acceptable form of birth control for the 30 days prior to the beginning of the study and agree to maintain adequate birth control measures during the whole duration of the study plus an additional 30 days as well as have a negative pregnancy test at screening Visit 3 and Visit 7.
Documented diagnosis of CP by medical history and it is preferred that it is supported by imaging evidence confirming CP which include: Abnormal ERCP [Endoscopic Retrograde Cholangio-Pancreatography] (Cambridge Class 4), Abnormal CT scan (dilated main pancreatic duct, atrophy of the pancreas or calcification) Abnormal Ultrasound, or Endoscopic Ultrasound with at least 5 abnormalities noted (V. Gupta and P.P. Toskes "Diagnosis and Management of Chronic Pancreatitis" Postgrad.Med.J: 2005; 81; 491-497)
In the case of pancreatic surgery, the patient can be included with partial or distal resection of the pancreas (not due to cancer)
Documented EPI with target Fecal Elastase ≤ 100 mcg/g of stool using the monoclonal test (Pancreatic Elastase 1 (PE1) by Genova Diagnostics) performed at the screening visit. The mean CV for the FE test is 20%.

Exclusion Criteria:

Patients known to the Investigator to have a significant medical and/or mental disease that would compromise the patient's welfare, pose an unacceptable risk to him/her or confound the study results
Participation in a clinical trial within 30 days of randomization or per specific country regulations/guidelines.
Cystic fibrosis
Excessive alcohol consumption
Drug abuse
Contraindicated or unable to discontinue prohibited concomitant medication, (see Section 5.2)
Uncontrolled diabetes mellitus that, according to the publication on Diabetes Care 25:S109, 2002 by the American Diabetes Association Inc., defines poor metabolic control of established diabetes, as follows:
- Hyperglycemia associated with volume depletion.
- Persistent refractory hyperglycemia associated with metabolic deterioration.
- Recurring fasting hyperglycemia >300 mg/dl (>16.7 mmol/l) that is refractory to outpatient therapy or an A1C level 100% above the upper limit of normal.
- Recurring episodes of severe hypoglycemia (i.e., <50 mg/dl [<2.8 mmol/l]) despite intervention.
- Metabolic instability manifested by frequent swings between hypoglycemia (<50 mg/dl [<2.8 mmol/l]) and fasting hyperglycemia (>300 mg/dl [>16.7 mmol/l]).
- Recurring diabetic ketoacidosis without precipitating infection or trauma.
- Repeated absence from school or work due to severe psychosocial problems causing poor metabolic control that cannot be managed on an outpatient basis.
Allergy to pork protein/ unwilling to ingest pork products
Atopic predisposition such as multiple drug hypersensitivity, allergic asthma, urticaria, or other relevant allergic diathesis
Pregnancy or lactation
Acute pancreatitis or acute exacerbation in chronic pancreatitis
Acute biliary disease
Malabsorption syndrome caused by a metabolic disease or by surgery, not related to exocrine pancreatic insufficiency
Any resection of the stomach or the gastrointestinal tract that will affect transit time and/or gastric emptying.
Evidence of active gastric or duodenal ulcer
Chronic inflammatory bowel disease
Any history of pancreatic cancer and other non- cutaneous malignancies (except basal cell and squamous cell carcinoma of the skin in situ that have been removed and not reoccurred in 5 years)
Viral hepatitis with infectious virions in blood and/or body fluids (any etiology)
HIV infection
Hyperuricemia ( > 1.5 times Upper Normal Value for lab)
Any acute or chronic disease, which in the opinion of the investigator could influence study results or pose a risk to the patient's safety.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00788593

Contacts

Contact: John Caminis, MD	267-759-9338	john.caminis@eurand.com
Contact: Candace Lee, RN	937-672-4838	clee@eurand.com

Locations

United States, Arkansas
Woodland International Research Group	Recruiting
Little Rock, Arkansas, United States, 72211
Principal Investigator: George Konis, MD
Sub-Investigator: Duong Nguyen, MD
Sub-Investigator: Jeanette Smith, RN
Sub-Investigator: Carol Witham, BS
Sub-Investigator: Todd Witham, LPN
Sub-Investigator: Dahlia Distin, RN
Sub-Investigator: Monica Haggans, RN
Sub-Investigator: Ashley Poole, BS
United States, California
HealthCare Partners Medical Group	Recruiting
Los Angeles, California, United States, 90015
Sub-Investigator: Timothy O'Connell, MD
Sub-Investigator: Bhasker Venkateswaralu, MD
Sub-Investigator: Francis Yemofio, MD
Principal Investigator: Gary Sutter, MD
United States, Florida
Advanced Medical Research Center	Recruiting
Port Orange, Florida, United States, 32127
Principal Investigator: Ammar Hemaiden, MD
Sub-Investigator: Alexander White, MD
Sub-Investigator: Saud Suleiman, MD
Sub-Investigator: Beatrice Beatrice Bratu, MD
Sub-Investigator: Hassan Zulfiqar, md
Sub-Investigator: Ahmed Shobassy, MD
Sub-Investigator: Jennifer E Stafford, PA
Sub-Investigator: Jullian P Johnson, PA
University of Florida, General Clinical Research Center	Recruiting
Gainesville, Florida, United States, 32610
Principal Investigator: Phillip P Toskes, MD
Sub-Investigator: John G Lieb, MD
Sub-Investigator: Dennis Collins, MD
Sub-Investigator: Peter Draganov, MD
Sub-Investigator: Nell Wade, RN
Sub-Investigator: Cheryl Currington
Sub-Investigator: Richard Coston
United States, Illinois
Veterans Affairs Edward Jr. Hines Hospital, Building #1	Recruiting
Hines, Illinois, United States, 60141
Principal Investigator: Stephen J Sontag, MD
Sub-Investigator: Thomas G Schnell, MD
Sub-Investigator: Jack Leya, MD
United States, Iowa
University of Iowa Hospitals and Clinics	Recruiting
Iowa Ctiy, Iowa, United States, 52242
Principal Investigator: Frederick C Johlin, MD
Sub-Investigator: Mary Panther
United States, Kentucky
University of Kentucky, Medical Center, Department of Gastroenterology	Recruiting
Lexington, Kentucky, United States, 40536
Principal Investigator: Nicholas J Nicki, MD
Sub-Investigator: Antonio Bosch, MD
Sub-Investigator: Houssam Mardini, MD
Sub-Investigator: Jeffrey Gilbert, MD
Sub-Investigator: Tammy Bryant, PA-C
Sub-Investigator: Sylvania L Nicholson, CCRC
Sub-Investigator: Robert Wells, MD
Sub-Investigator: Sarah M Turner
Sub-Investigator: Thomas Knopp, MD
Sub-Investigator: Matthew Ashmun, MD
Sub-Investigator: Patrick Mosler, MD
Sub-Investigator: Alla Grigorian, MD
University of Louisville, Carmichael Building	Recruiting
Louisville, Kentucky, United States, 40202
Principal Investigator: John M Wo, MD
Sub-Investigator: Gerald W Dryden, MD
Sub-Investigator: Richard A Wright, MD
Sub-Investigator: Matthew D McCollough, MD
Sub-Investigator: Emori B Bizer, MD
Sub-Investigator: Jonathan W Goldstein, MD
Sub-Investigator: Robert R Tatum, PharmD, PA-C
Sub-Investigator: Kristine J Krueger, MD
Sub-Investigator: Karen S Beatty, RN
United States, Missouri
University of Missouri Health Care	Recruiting
Columbia, Missouri, United States, 65212
Principal Investigator: Mainor Antillion, MD
Sub-Investigator: Wilson Pais, MD
Italy, Bologna
Dipartmento di Malattie dell' apparato digerente e Medicina Interna- Unita Operativa di MedicinaInterna Corinaldesi Azienda Ospedaliero- Universitaria Policlinico Sant'Orsola Malpighi Via Massarenti	Recruiting
Massarenti, Bologna, Italy, 9-40138
Principal Investigator: Raffaele Pezzilli, MD
Sub-Investigator: Andrea Lioce, MD
Italy, Milano
Istituto Clinico Humanitas - Universita' Di Milano Via Manzoni	Recruiting
Rozzano, Milano, Italy, 20089
Principal Investigator: Alberto Malesci
Sub-Investigator: Paolo Omodei, MD
Sub-Investigator: Orsola Sociale
Sub-Investigator: Manuela Pastore
Sub-Investigator: Paoletta Preatoni, MD
Italy, Roma
Istituto di Clinica Chirurgica (Ensoscopia Digestive Chirurgica) Policlinico Gemelli-Universita Cattolica del Sacro Cuore	Recruiting
Largo Agostino Gemelli, Roma, Italy, 8 00168
Principal Investigator: Guido Costamagna, MD
Sub-Investigator: Andrea Tringali, MD
Sub-Investigator: Ivo Boskoski, MD
Italy, Verona
Centro Richerche Cliniche di Verona	Recruiting
le Ludovico Scuro, Verona, Italy, 10 37134
Principal Investigator: Fosca De Iorio
Sub-Investigator: Christina Papadopoulou
Sub-Investigator: Luigi Fondrieschi
Sub-Investigator: Gabriella Amen
Sub-Investigator: Luigi Ziviani
Sub-Investigator: Vittorio Schweiger
Ukraine
Department of Internal Medicine No 2 of Donetsk State University named after M. Gorkly, City Clinical Hospital No 3	Recruiting
Donetsk, Ukraine, 83017
Principal Investigator: Andrly Dorofyeyev
Sub-Investigator: Olga Rassokhina, MD
Sub-Investigator: Oleg Tomash, MD
Sub-Investigator: Nikolay Rudenko, MD
Ukraine, Crimea
Department of Therapy and Family Medicine of the Facility of Post graduate Education of Crimea State Medical University named after S.I. Georglyevskyy Republic Clinical Hospital named after M.O. Semashko	Recruiting
Simferopol, Crimea, Ukraine, 95017
Principal Investigator: Iryna Klyaryts'ka
Sub-Investigator: Tetyana Tsapyak, MD
Sub-Investigator: Iryna Iskova, MD
Sub-Investigator: Lyudmila Semenova, MD
Sub-Investigator: Svetlana Gorbadey
Ukraine, Kharklv
Department of Liver and Gastrointestinal Tract Disease Institute of Therapy named after L.T. Maylaya of Academy of Medical Sciences of the Ukraine	Recruiting
Kharkiv, Kharklv, Ukraine, 61039
Principal Investigator: Galyna Fadielenko
Sub-Investigator: Oleksly Gridnyev, MD
Sub-Investigator: Valentyna Chernova Valentyna Chernova, MD
Sub-Investigator: Inna Klimova
Sub-Investigator: Inna Ryabovol
Ukraine, Kylv
Department of Faculty Therapy No 1 with the Course of Postgraduate Training of Physicians for Gastroenterology and Endoscopy, National Medical University named after O.O. Bogomolets, City Hospital No 18	Recruiting
Kyiv, Kylv, Ukraine, 01030
Principal Investigator: Larysa Dudar
Sub-Investigator: Luisa Parunian, MD
Sub-Investigator: Tetyana Kovalyova
Sub-Investigator: Nina Rudenok
General Therapy Clinic, Military Clinical Hospital of Ministry of Defense of Ukraine 18	Recruiting
Kyiv, Kylv, Ukraine, 01133
Principal Investigator: Sergil Simonov, MD
Sub-Investigator: Sergly Prokopchuk, MD

Sponsors and Collaborators

Eurand S.p.A.

Investigators

Principal Investigator:

Phillip Toskes, MD

University of Florida, Department of Medicine, Division of Gastroenterology

Responsible Party:	University of Florida Department of Medicine, Division of Gastroenterology ( Phillip P. Toskes, MD )
Study ID Numbers:	PR-002
Study First Received:	November 10, 2008
Last Updated:	November 10, 2008
ClinicalTrials.gov Identifier:	NCT00788593
Health Authority:	United States: Food and Drug Administration; Ukraine: State Pharmacological Center - Ministry of Health; Italy: National Monitoring Centre for Clinical Trials - Ministry of Health