A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 (APT-1008) in Chronic Pancreatitis (CP) Participants With Exocrine Pancreatic Insufficiency (EPI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Aptalis Pharma
ClinicalTrials.gov Identifier:
NCT00788593
First received: November 10, 2008
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

The primary efficacy objective of this study is to evaluate the difference in coefficient of fat absorption (CFA) of participants treated with high dose EUR-1008 (APT-1008) versus low dose of EUR-1008 (APT-1008) in the treatment of signs and symptoms of malabsorption in participants with EPI associated with CP. This study is sponsored by Aptalis Pharma (formerly Eurand).


Condition Intervention Phase
Chronic Pancreatitis
Exocrine Pancreatic Insufficiency
Drug: Placebo
Drug: EUR-1008 (APT-1008) High Dose
Drug: EUR-1008 (APT-1008) Low Dose
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 in Chronic Pancreatitis (CP) Patients With Exocrine Pancreatic Insufficiency (EPI)

Resource links provided by NLM:


Further study details as provided by Aptalis Pharma:

Primary Outcome Measures:
  • Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008 [ Time Frame: 3 to 5 days of hospital treatment in first and second intervention periods ] [ Designated as safety issue: No ]
    Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools collected during the 72-hour CFA determination period. Mean percent CFA was calculated for the 3 to 5 days of hospital treatment in first and second intervention periods.


Secondary Outcome Measures:
  • Change From Placebo Baseline in Percent Coefficient of Fat Absorption (CFA) in High Dose EUR-1008 and Low Dose EUR-1008 During Hospital Treatment [ Time Frame: Baseline, 3 to 5 days of hospital treatment in first and second intervention periods ] [ Designated as safety issue: No ]
    Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools collected during the 72-hour CFA determination period. Mean percent CFA was calculated for 3 to 5 days of hospital treatment in first and second intervention periods.

  • Change From Placebo Baseline in Percent Coefficient of Nitrogen Absorption (CNA) During Hospital Treatment [ Time Frame: Baseline, 3 to 5 days of hospital treatment in first and second intervention periods ] [ Designated as safety issue: No ]
    Percent CNA was calculated as [(nitrogen intake - nitrogen excretion)/nitrogen intake]*100 , determined in the stools collected during the 72-hour CNA determination period. Nitrogen intake was calculated as protein intake/6.2. Nitrogen excretion was measured as total fecal nitrogen. Mean percent CNA was calculated for 3 to 5 days of hospital treatment in first and second intervention periods.

  • Change From Placebo Baseline in Weight at End of Each Treatment Period [ Time Frame: Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods) ] [ Designated as safety issue: No ]
    Mean change from baseline in weight was calculated for end of treatment (6 days home treatment and 3-5 days hospital treatment) in first and second intervention periods.

  • Change From Placebo Baseline in Body Mass Index (BMI) at End of Treatment [ Time Frame: Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods) ] [ Designated as safety issue: No ]
    BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2). Mean change from baseline in BMI was calculated for end of treatment (6 days home treatment and 3-5 days hospital treatment) in first and second intervention periods.


Enrollment: 82
Study Start Date: January 2008
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo matching to EUR-1008 (APT-1008) capsules orally daily for 4 days home treatment and 3 to 5 days hospital treatment in the baseline run-in phase, which will then be randomized to either high dose or low dose of EUR-1008 (APT-1008).
Experimental: EUR-1008 (APT-1008) High Dose Drug: EUR-1008 (APT-1008) High Dose
EUR-1008 (APT-1008) total high dose 140,000 lipase USP Lipase units will be given as 7 capsules containing 20,000 USP Lipase units each, orally daily, distributed over the day per gram of fat in diet (possible example: 2 capsules with breakfast, 2 capsules with lunch, 2 capsules with dinner and 1 capsule with a snack) for 6 days home treatment and 3 to 5 days hospital treatment in either first intervention period or second intervention period.
Other Name: Zenpep
Experimental: EUR-1008 (APT-1008) Low Dose Drug: EUR-1008 (APT-1008) Low Dose
EUR-1008 (APT-1008) total low dose 35,000 lipase USP Lipase units will be given as 7 capsules containing 5,000 USP Lipase units each, orally daily, distributed over the day per gram of fat in diet (possible example: 2 capsules with breakfast, 2 capsules with lunch, 2 capsules with dinner and 1 capsule with a snack) for 6 days home treatment and 3 to 5 days hospital treatment in either first intervention period or second intervention period.
Other Name: Zenpep

Detailed Description:

After screening, eligible participants 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, participants will be randomized to a "high dose followed by a low dose" or to a "low dose followed by a high dose" EUR-1008 (APT-1008) dose sequence and proceed to the first crossover (treatment) phase. Each crossover (treatment) 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.

Participants will immediately proceed from the first crossover (treatment) phase to the second without a washout period or return-to-baseline period in between phases. Participants 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 participants 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:

  • Participants are male or female
  • Participants with age over 18 years
  • Participants who have 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
  • Participants with documented diagnosis of CP by medical history and it is preferred that it is supported by imaging evidence confirming CP which include: abnormal endoscopic retrograde cholangio-pancreatography (ERCP) (Cambridge Class 4), abnormal computed tomography (CT) scan (dilated main pancreatic duct, atrophy of the pancreas or calcification), abnormal ultrasound, or endoscopic ultrasound with at least 5 abnormalities noted
  • In the case of pancreatic surgery, the participant can be included with partial or distal resection of the pancreas (not due to cancer)
  • Participants with documented EPI with target fecal elastase (FE) less than or equal to 100 microgram per gram (mcg/g) of stool using the monoclonal test (pancreatic elastase 1 [PE1] by Genova Diagnostics) performed at the screening visit. The mean coefficient of variation (CV) for the FE test is 20 percent (%)

Exclusion Criteria:

  • Participants known to the investigator to have a significant medical and/or mental disease that would compromise the participant's welfare, pose an unacceptable risk to him/her or confound the study results
  • Participants who participated in a clinical trial within 30 days of randomization or per specific country regulations/guidelines
  • Participants with cystic fibrosis
  • Participants with excessive alcohol consumption
  • Participants with drug abuse
  • Participants with contraindicated medications or who are unable to discontinue prohibited concomitant medication
  • Participants with uncontrolled diabetes mellitus
  • Participants allergic to pork protein/unwilling to ingest pork products
  • Participants with atopic predisposition such as multiple drug hypersensitivity, allergic asthma, urticaria, or other relevant allergic diathesis
  • Participants who are pregnant or lactating
  • Participants with acute pancreatitis or acute exacerbation in chronic pancreatitis
  • Participants with acute biliary disease
  • Participants with malabsorption syndrome caused by a metabolic disease or by surgery, not related to exocrine pancreatic insufficiency
  • Participants with any resection of the stomach or the gastrointestinal tract that will affect transit time and/or gastric emptying.
  • Participants with evidence of active gastric or duodenal ulcer
  • Participants with chronic inflammatory bowel disease
  • Participants with 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)
  • Participants with viral hepatitis with infectious virions in blood and/or body fluids (any etiology)
  • Participants with human immunodeficiency virus (HIV) infection
  • Participants with hyperuricemia ( greater than [>] 1.5 times upper normal value for lab)
  • Participants with any acute or chronic disease, which in the opinion of the investigator could influence study results or pose a risk to the participants' safety
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00788593

Locations
United States, Arkansas
Woodland International Research Group
Little Rock, Arkansas, United States, 72211
United States, California
HealthCare Partners Medical Group
Los Angeles, California, United States, 90015
United States, Florida
University of Florida, General Clinical Research Center
Gainesville, Florida, United States, 32610
Advanced Medical Research Center
Port Orange, Florida, United States, 32127
United States, Illinois
Veterans Affairs Edward Jr. Hines Hospital, Building #1
Hines, Illinois, United States, 60141
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa Ctiy, Iowa, United States, 52242
United States, Kentucky
University of Kentucky, Medical Center, Department of Gastroenterology
Lexington, Kentucky, United States, 40536
University of Louisville, Carmichael Building
Louisville, Kentucky, United States, 40202
United States, Missouri
University of Missouri Health Care
Columbia, Missouri, United States, 65212
Italy
Dipartmento di Malattie dell' apparato digerente e Medicina Interna- Unita Operativa di MedicinaInterna Corinaldesi Azienda Ospedaliero- Universitaria Policlinico Sant'Orsola Malpighi Via Massarenti
Massarenti, Bologna, Italy, 9-40138
Istituto Clinico Humanitas - Universita' Di Milano Via Manzoni
Rozzano, Milano, Italy, 20089
Istituto di Clinica Chirurgica (Ensoscopia Digestive Chirurgica) Policlinico Gemelli-Universita Cattolica del Sacro Cuore
Largo Agostino Gemelli, Roma, Italy, 8 00168
Centro Richerche Cliniche di Verona
le Ludovico Scuro, Verona, Italy, 10 37134
Ukraine
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
Simferopol, Crimea, Ukraine, 95017
Department of Liver and Gastrointestinal Tract Disease Institute of Therapy named after L.T. Maylaya of Academy of Medical Sciences of the Ukraine
Kharkiv, Kharklv, Ukraine, 61039
General Therapy Clinic, Military Clinical Hospital of Ministry of Defense of Ukraine 18
Kyiv, Kylv, Ukraine, 01133
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
Kyiv, Kylv, Ukraine, 01030
Department of Internal Medicine No 2 of Donetsk State University named after M. Gorkly, City Clinical Hospital No 3
Donetsk, Ukraine, 83017
Sponsors and Collaborators
Aptalis Pharma
Investigators
Study Director: Aptalis Medical Information Aptalis Pharma
  More Information

No publications provided

Responsible Party: Aptalis Pharma
ClinicalTrials.gov Identifier: NCT00788593     History of Changes
Other Study ID Numbers: PR-002
Study First Received: November 10, 2008
Results First Received: January 27, 2014
Last Updated: January 27, 2014
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

Keywords provided by Aptalis Pharma:
Chronic Pancreatitis
Exocrine Pancreatic Insufficiency

Additional relevant MeSH terms:
Exocrine Pancreatic Insufficiency
Pancreatitis
Pancreatitis, Chronic
Pancreatic Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 17, 2014