Clinical 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)
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
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 Exocrin
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 Summary:
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.
Sponsor: Forest Laboratories
Current Primary Outcome: 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 ]
Original Primary Outcome: The primary analysis conducted on all patients who complete both the high dose and low dose. An additional analysis will be conducted to calculate the difference between the mean CFA after administration of doses after administration. [ Time Frame: 78 days ]
Current Secondary Outcome:
- 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 ]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 ]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) ]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) ]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.
Original Secondary Outcome: Calculation of the differences in CFA of patients on high dose EUR-1008 vs. CFA at placebo baseline and patients on low dose EUR-1008 vs. CFA at placebo baseline. Change in the CNA from baseline. Change in weight and BMI from baseline [ Time Frame: 78 days ]
Information By: Forest Laboratories
Dates:
Date Received: November 10, 2008
Date Started: January 2008
Date Completion:
Last Updated: January 27, 2014
Last Verified: January 2014
