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)

NCT00788593 | Completed Phase 3 Results

• 1 other identifier: PR-002
• Study Type: interventional
• Target: 82
• Locations: 3 countries
• Sites: 18

Brief Summary

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).

Conditions

Chronic Pancreatitis; Exocrine Pancreatic Insufficiency

Keywords

Chronic Pancreatitis; Exocrine Pancreatic Insufficiency

Outcome Measures

Primary Outcomes (1)

• Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008

  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.

  3 to 5 days of hospital treatment in first and second intervention periods

Secondary Outcomes (4)

• Change From Placebo Baseline in Percent Coefficient of Fat Absorption (CFA) in High Dose EUR-1008 and Low Dose EUR-1008 During Hospital Treatment

  Baseline, 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

  Baseline, 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

  Baseline, 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

  Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

EUR-1008 (APT-1008) High Dose

EXPERIMENTAL

Drug: EUR-1008 (APT-1008) High Dose

EUR-1008 (APT-1008) Low Dose

EXPERIMENTAL

Drug: EUR-1008 (APT-1008) Low Dose

Interventions

Placebo DRUG

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).

Placebo

EUR-1008 (APT-1008) High Dose DRUG

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.

Also known as: Zenpep

EUR-1008 (APT-1008) High Dose

EUR-1008 (APT-1008) Low Dose DRUG

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.

Also known as: Zenpep

EUR-1008 (APT-1008) Low Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (%)

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead

Study Sites (18)

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

HealthCare Partners Medical Group

Los Angeles, California, 90015, United States

Location

University of Florida, General Clinical Research Center

Gainesville, Florida, 32610, United States

Location

Advanced Medical Research Center

Port Orange, Florida, 32127, United States

Location

Veterans Affairs Edward Jr. Hines Hospital, Building #1

Hines, Illinois, 60141, United States

Location

University of Iowa Hospitals and Clinics

Iowa Ctiy, Iowa, 52242, United States

Location

University of Kentucky, Medical Center, Department of Gastroenterology

Lexington, Kentucky, 40536, United States

Location

University of Louisville, Carmichael Building

Louisville, Kentucky, 40202, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65212, United States

Location

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, 9-40138, Italy

Location

Istituto Clinico Humanitas - Universita' Di Milano Via Manzoni

Rozzano, Milano, 20089, Italy

Location

Istituto di Clinica Chirurgica (Ensoscopia Digestive Chirurgica) Policlinico Gemelli-Universita Cattolica del Sacro Cuore

Largo Agostino Gemelli, Roma, 8 00168, Italy

Location

Centro Richerche Cliniche di Verona

Le Ludovico Scuro, Verona, 10 37134, Italy

Location

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, Autonomous Republic of Crimea, 95017, Ukraine

Location

Department of Internal Medicine No 2 of Donetsk State University named after M. Gorkly, City Clinical Hospital No 3

Donetsk, Donetsk Oblast, 83017, Ukraine

Location

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, 61039, Ukraine

Location

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, 01030, Ukraine

Location

General Therapy Clinic, Military Clinical Hospital of Ministry of Defense of Ukraine 18

Kyiv, Kylv, 01133, Ukraine

Location

MeSH Terms

Conditions

Pancreatitis, Chronic; Exocrine Pancreatic Insufficiency

Interventions

Pancrelipase

Condition Hierarchy (Ancestors)

Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lipase; Carboxylic Ester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pancreatic Extracts; Tissue Extracts; Complex Mixtures

Results Point of Contact

• Title: Robert Winkler, MD, VP, Clinical Development and Operations
• Organization: Aptalis Pharma US, Inc.

1-800-472-2634

Study Officials

• Aptalis Medical Information

  Forest Laboratories

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2008
• First Posted: November 11, 2008
• Study Start: January 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: March 12, 2014
• Results First Posted: March 12, 2014

Record last verified: 2014-01

Locations

US (9); UA (5); IT (4)