Clinical trial NCT00788593: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Pancreatitis
Exocrine Pancreatic Insufficiency
Keywords: Chronic Pancreatitis
Exocrine Pancreatic Insufficiency
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2008-11-11
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008
timeFrame: 3 to 5 days of hospital treatment in first and second intervention periods
Secondary outcomes:
measure: Change From Placebo Baseline in Percent Coefficient of Fat Absorption (CFA) in High Dose EUR-1008 and Low Dose EUR-1008 During Hospital Treatment
timeFrame: Baseline, 3 to 5 days of hospital treatment in first and second intervention periods
measure: Change From Placebo Baseline in Percent Coefficient of Nitrogen Absorption (CNA) During Hospital Treatment
timeFrame: Baseline, 3 to 5 days of hospital treatment in first and second intervention periods
measure: Change From Placebo Baseline in Weight at End of Each Treatment Period
timeFrame: Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods)
measure: Change From Placebo Baseline in Body Mass Index (BMI) at End of Treatment
timeFrame: Baseline, end of treatment (6 days home treatment and 3-5 days hospital treatment in first and second intervention periods)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Los Angeles
country: United States
facility: HealthCare Partners Medical Group
state: California
city: Gainesville
country: United States
facility: University of Florida, General Clinical Research Center
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Hines
country: United States
facility: Veterans Affairs Edward Jr. Hines Hospital, Building #1
state: Illinois
city: Iowa Ctiy
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky, Medical Center, Department of Gastroenterology
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville, Carmichael Building
state: Kentucky
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Massarenti
country: Italy
facility: Dipartmento di Malattie dell' apparato digerente e Medicina Interna- Unita Operativa di MedicinaInterna Corinaldesi Azienda Ospedaliero- Universitaria Policlinico Sant'Orsola Malpighi Via Massarenti
state: Bologna
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas - Universita' Di Milano Via Manzoni
state: Milano
city: Largo Agostino Gemelli
country: Italy
facility: Istituto di Clinica Chirurgica (Ensoscopia Digestive Chirurgica) Policlinico Gemelli-Universita Cattolica del Sacro Cuore
state: Roma
city: le Ludovico Scuro
country: Italy
facility: Centro Richerche Cliniche di Verona
state: Verona
city: Simferopol
country: Ukraine
facility: 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
state: Crimea
city: Kharkiv
country: Ukraine
facility: Department of Liver and Gastrointestinal Tract Disease Institute of Therapy named after L.T. Maylaya of Academy of Medical Sciences of the Ukraine
state: Kharklv
city: Kyiv
country: Ukraine
facility: 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
state: Kylv
city: Kyiv
country: Ukraine
facility: General Therapy Clinic, Military Clinical Hospital of Ministry of Defense of Ukraine 18
state: Kylv
city: Donetsk
country: Ukraine
facility: Department of Internal Medicine No 2 of Donetsk State University named after M. Gorkly, City Clinical Hospital No 3
Study officials:
affiliation: Forest Laboratories
name: Aptalis Medical Information
role: STUDY_DIRECTOR
References: