Trial Outcomes & Findings for Safety and Efficacy Study of Viokase® 16 for the Correction of Steatorrhea (NCT NCT00559364)

Last Updated: 2017-03-16

Results Overview

Percent CFA was calculated as (\[fat intake - fat excretion\]/fat intake)\*100, determined in the stools which was collected from Day 1 to Day 4 or Day 5 during the inpatient period of treatment phase. Mean percent (%) CFA was calculated for Day 1 to Day 4 or Day 5 in inpatient period of treatment phase.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

50 participants

Primary outcome timeframe

Day 1 up to Day 4 or Day 5 in inpatient period of treatment phase

Results posted on

2017-03-16

Participant Flow

Patients underwent screening phase (up to 10 days) and wash-out phase (6 to 7 days, where baseline coefficient of fat absorption \[CFA\] was determined) before entering randomization phase. Out of 218 patients, who entered screening and washout phases, 168 discontinued due to screen failure; 50 patients were randomized to treatment phase.

Participant milestones

Participant milestones
Measure	Viokase® Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Overall Study STARTED	30	20
Overall Study COMPLETED	29	20
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Viokase® Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Overall Study Inclusion/exclusion criteria failure	1	0

Baseline Characteristics

Safety and Efficacy Study of Viokase® 16 for the Correction of Steatorrhea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Viokase® n=30 Participants Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo n=20 Participants Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Total n=50 Participants Total of all reporting groups
Age, Continuous	50.9 years STANDARD_DEVIATION 9.91 • n=99 Participants	50.6 years STANDARD_DEVIATION 7.63 • n=107 Participants	50.8 years STANDARD_DEVIATION 8.98 • n=206 Participants
Sex: Female, Male Female	8 Participants n=99 Participants	1 Participants n=107 Participants	9 Participants n=206 Participants
Sex: Female, Male Male	22 Participants n=99 Participants	19 Participants n=107 Participants	41 Participants n=206 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 4 or Day 5 in inpatient period of treatment phase

Population: Intent-to-treat (ITT) population included all randomized patients. Missing values at treatment phase were imputed using the median (50th percentile) of all non-missing values within a treatment group.

Outcome measures

Outcome measures
Measure	Viokase® n=30 Participants Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo n=20 Participants Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Percent Coefficient of Fat Absorption (CFA)	85.52 percent CFA Standard Deviation 8.902	58.02 percent CFA Standard Deviation 24.249

SECONDARY outcome

Timeframe: Day 1 up to Day 4 or Day 5 in inpatient period of treatment phase

Population: ITT population included all randomized patients.

Mean daily number of stools of each patient was calculated from frequency of stools by the patient per day. Mean daily number of stools during the collection period (Day 1 to Day 4 or Day 5 in inpatient period of treatment phase) for total patients was summarized.

Outcome measures

Outcome measures
Measure	Viokase® n=30 Participants Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo n=20 Participants Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Mean Daily Number of Stools	1.93 stools per day Standard Deviation 0.989	2.33 stools per day Standard Deviation 0.950

SECONDARY outcome

Timeframe: Day 1 up to Day 4 or Day 5 in inpatient period of treatment phase

Population: ITT population included all randomized patients.

Stool consistency was categorized as hard, formed/normal, soft and watery. Percentage of stools of a specific consistency for each patient was calculated as: (total number of stools of specific consistency during the completed days of the inpatient period/ total number of stools during the completed days of the inpatient period)\*100. Mean percentage of stool categorized as per consistency for total patients was summarized.

Outcome measures

Outcome measures
Measure	Viokase® n=30 Participants Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo n=20 Participants Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Percentage of Stools Categorized as Per Consistency Hard stools	5.08 percentage of stools Standard Deviation 13.61	0.67 percentage of stools Standard Deviation 2.98
Percentage of Stools Categorized as Per Consistency Formed/normal stools	45.86 percentage of stools Standard Deviation 33.27	37.23 percentage of stools Standard Deviation 37.91
Percentage of Stools Categorized as Per Consistency Soft stools	47.80 percentage of stools Standard Deviation 33.31	55.48 percentage of stools Standard Deviation 39.46
Percentage of Stools Categorized as Per Consistency Watery stools	1.26 percentage of stools Standard Deviation 4.82	5.80 percentage of stools Standard Deviation 14.57

Adverse Events

Viokase®

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Viokase® n=30 participants at risk Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo n=20 participants at risk Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Hepatobiliary disorders Cholelithiasis	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Cardiac disorders Cardiac failure	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Investigations Coagulation factor decreased	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
General disorders Disease progression	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.

Other adverse events

Other adverse events
Measure	Viokase® n=30 participants at risk Patients received Viokase® 16, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.	Placebo n=20 participants at risk Patients received matching placebo, 22 tablets orally daily (that is, 6 tablets per meal and 2 tablets with 2 of 3 snacks) for 6 to 7 days in treatment phase. Patients on proton pump inhibitor (PPI) therapy during Screening continued their usual (those not using PPI therapy at screening received omeprazole 20 milligram orally once daily) throughout the study.
Blood and lymphatic system disorders Anaemia	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Gastrointestinal disorders Anal pruritus	6.7% 2/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Gastrointestinal disorders Abdominal pain	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Gastrointestinal disorders Ascites	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Gastrointestinal disorders Flatulence	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
General disorders Oedema peripheral	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Hepatobiliary disorders Bile duct stone	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Hepatobiliary disorders Hydrocholecystis	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Infections and infestations Viral infection	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	5.0% 1/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Nervous system disorders Headache	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Renal and urinary disorders Renal cyst	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	5.0% 1/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.
Skin and subcutaneous tissue disorders Rash	3.3% 1/30 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.	0.00% 0/20 • Day 1 of treatment phase up to 30 days after last dose administration Adverse event (AE) was any untoward medical occurrence regardless of causal relationship to study drug. Serious AE was any event that resulted in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was a congenital anomaly/birth defect or is assessed as important medical event.

Additional Information

Robert Winkler, MD, VP, Clinical Development and Operations

Aptalis Pharma US, Inc.

Phone: 1-800-472-2634

Results disclosure agreements

Principal investigator is a sponsor employee Restrictions vary in accordance with each agreement with the individual investigators. Sponsor will allow publication but will prohibit disclosure of Sponsor's confidential information within any publication and can defer publication for a period of time to allow for Sponsor to obtain patent or other intellectual property right protection.
Publication restrictions are in place

Restriction type: OTHER