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)

Phase 3

Completed

Conditions: Chronic Pancreatitis
Exocrine Pancreatic Insufficiency

Interventions: Drug: Placebo
Drug: EUR-1008 (APT-1008) High Dose
Drug: EUR-1008 (APT-1008) Low Dose

Registration Number: NCT00788593

Lead Sponsor: Forest Laboratories

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
EUR-1008 (APT-1008) High Dose	EUR-1008 (APT-1008) High Dose	-
EUR-1008 (APT-1008) Low Dose	EUR-1008 (APT-1008) Low Dose	-

Primary Outcome Measures

Name	Time	Method
Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008	3 to 5 days of hospital treatment in first and second intervention periods	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

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

Trial Locations

Locations (18): University of Missouri Health Care
🇺🇸
Columbia, Missouri, United States
Veterans Affairs Edward Jr. Hines Hospital, Building #1
🇺🇸
Hines, Illinois, United States
HealthCare Partners Medical Group
🇺🇸
Los Angeles, California, United States
University of Kentucky, Medical Center, Department of Gastroenterology
🇺🇸
Lexington, Kentucky, United States
Advanced Medical Research Center
🇺🇸
Port Orange, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa Ctiy, Iowa, United States
University of Florida, General Clinical Research Center
🇺🇸
Gainesville, Florida, United States
Department of Internal Medicine No 2 of Donetsk State University named after M. Gorkly, City Clinical Hospital No 3
🇺🇦
Donetsk, Ukraine
University of Louisville, Carmichael Building
🇺🇸
Louisville, Kentucky, United States
Istituto Clinico Humanitas - Universita' Di Milano Via Manzoni
🇮🇹
Rozzano, Milano, Italy
Istituto di Clinica Chirurgica (Ensoscopia Digestive Chirurgica) Policlinico Gemelli-Universita Cattolica del Sacro Cuore
🇮🇹
Largo Agostino Gemelli, Roma, Italy
Centro Richerche Cliniche di Verona
🇮🇹
le Ludovico Scuro, Verona, Italy
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
Woodland International Research Group
🇺🇸
Little Rock, Arkansas, United States
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
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
General Therapy Clinic, Military Clinical Hospital of Ministry of Defense of Ukraine 18
🇺🇦
Kyiv, Kylv, 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
🇺🇦
Kyiv, Kylv, Ukraine