search
Back to results

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)

Primary Purpose

Chronic Pancreatitis, Exocrine Pancreatic Insufficiency

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
EUR-1008 (APT-1008) High Dose
EUR-1008 (APT-1008) Low Dose
Sponsored by
Forest Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Pancreatitis focused on measuring Chronic Pancreatitis, Exocrine Pancreatic Insufficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Woodland International Research Group
  • HealthCare Partners Medical Group
  • University of Florida, General Clinical Research Center
  • Advanced Medical Research Center
  • Veterans Affairs Edward Jr. Hines Hospital, Building #1
  • University of Iowa Hospitals and Clinics
  • University of Kentucky, Medical Center, Department of Gastroenterology
  • University of Louisville, Carmichael Building
  • University of Missouri Health Care
  • Dipartmento di Malattie dell' apparato digerente e Medicina Interna- Unita Operativa di MedicinaInterna Corinaldesi Azienda Ospedaliero- Universitaria Policlinico Sant'Orsola Malpighi Via Massarenti
  • Istituto Clinico Humanitas - Universita' Di Milano Via Manzoni
  • Istituto di Clinica Chirurgica (Ensoscopia Digestive Chirurgica) Policlinico Gemelli-Universita Cattolica del Sacro Cuore
  • Centro Richerche Cliniche di Verona
  • 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
  • Department of Liver and Gastrointestinal Tract Disease Institute of Therapy named after L.T. Maylaya of Academy of Medical Sciences of the Ukraine
  • 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
  • General Therapy Clinic, Military Clinical Hospital of Ministry of Defense of Ukraine 18
  • Department of Internal Medicine No 2 of Donetsk State University named after M. Gorkly, City Clinical Hospital No 3

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

EUR-1008 (APT-1008) High Dose

EUR-1008 (APT-1008) Low Dose

Arm Description

Outcomes

Primary Outcome Measures

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.

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
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
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
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
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.

Full Information

First Posted
November 10, 2008
Last Updated
January 27, 2014
Sponsor
Forest Laboratories
search

1. Study Identification

Unique Protocol Identification Number
NCT00788593
Brief Title
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)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forest Laboratories

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pancreatitis, Exocrine Pancreatic Insufficiency
Keywords
Chronic Pancreatitis, Exocrine Pancreatic Insufficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
EUR-1008 (APT-1008) High Dose
Arm Type
Experimental
Arm Title
EUR-1008 (APT-1008) Low Dose
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
EUR-1008 (APT-1008) High Dose
Other Intervention Name(s)
Zenpep
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
EUR-1008 (APT-1008) Low Dose
Other Intervention Name(s)
Zenpep
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008
Description
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.
Time Frame
3 to 5 days of hospital treatment in first and second intervention periods
Secondary Outcome Measure Information:
Title
Change From Placebo Baseline in Percent Coefficient of Fat Absorption (CFA) in High Dose EUR-1008 and Low Dose EUR-1008 During Hospital Treatment
Description
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.
Time Frame
Baseline, 3 to 5 days of hospital treatment in first and second intervention periods
Title
Change From Placebo Baseline in Percent Coefficient of Nitrogen Absorption (CNA) During Hospital Treatment
Description
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.
Time Frame
Baseline, 3 to 5 days of hospital treatment in first and second intervention periods
Title
Change From Placebo Baseline in Weight at End of Each Treatment Period
Description
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.
Time Frame
Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods)
Title
Change From Placebo Baseline in Body Mass Index (BMI) at End of Treatment
Description
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.
Time Frame
Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods)

10. Eligibility

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

12. IPD Sharing Statement

Learn more about this trial

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)

We'll reach out to this number within 24 hrs