Trial Outcomes & Findings for Use of Ultrase® MT12 in Young Cystic Fibrosis Children (CF) (NCT NCT00880100)

NCT ID: NCT00880100

Last Updated: 2017-03-16

Results Overview

Control of steatorrhea was defined as a less than 30 percent (%) of fat in stools as measured by nuclear magnetic resonance (NMR) spectroscopy in all stool samples which are collected at baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and during the 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 49 participants
• Primary outcome timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)
• Results posted on: 2017-03-16

Participant Flow

The enrollment started in April 2009 and was completed in November 2009. Cystic fibrosis (CF) patients with pancreatic insufficiency (PI), aged 2 to 6 years old inclusively, were enrolled from 14 CF centers located in United States of America.

Participant milestones

Measure	Ultrase® MT12 Patients received usual pancreatic enzymes therapy for 9 to 14 days during baseline phase followed by Ultrase® MT12 capsules orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Baseline Phase-Usual Pancreatic Enzymes STARTED	49
Baseline Phase-Usual Pancreatic Enzymes COMPLETED	48
Baseline Phase-Usual Pancreatic Enzymes NOT COMPLETED	1
Treatment Phase With Ultrase® MT12 STARTED	48
Treatment Phase With Ultrase® MT12 COMPLETED	45
Treatment Phase With Ultrase® MT12 NOT COMPLETED	3

Reasons for withdrawal

Measure	Ultrase® MT12 Patients received usual pancreatic enzymes therapy for 9 to 14 days during baseline phase followed by Ultrase® MT12 capsules orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Baseline Phase-Usual Pancreatic Enzymes Protocol Violation	1
Treatment Phase With Ultrase® MT12 Adverse Event	1
Treatment Phase With Ultrase® MT12 Protocol Violation	2

Baseline Characteristics

Use of Ultrase® MT12 in Young Cystic Fibrosis Children (CF)

Baseline characteristics by cohort

Measure	Ultrase® MT12 n=48 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Age, Categorical <=18 years	48 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	3.8 years STANDARD_DEVIATION 1.42 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The Intent-to-treat (ITT) population included all patients who signed an informed consent form (ICF) and started the baseline phase. The 50th percentile imputation method was used for missing data.

Control of steatorrhea was defined as a less than 30 percent (%) of fat in stools as measured by nuclear magnetic resonance (NMR) spectroscopy in all stool samples which are collected at baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and during the 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Percentage of Patients With Control of Steatorrhea Baseline phase (usual pancreatic enzymes)	46.9 percentage of patients Interval 32.5 to 61.7
Percentage of Patients With Control of Steatorrhea Treatment phase	42.9 percentage of patients Interval 28.8 to 57.8

SECONDARY outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. Here "n" signifies patients who were evaluable for each specified category.

Normal stool frequency was defined as having less than 4 bowel movements per day in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the Treatment Phase during which the PEP was replaced with Ultrase MT12.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Percentage of Patients With Normal Stool Frequency Baseline phase (usual pancreatic enzymes): n=49	87.8 percentage of patients Interval 75.2 to 95.4
Percentage of Patients With Normal Stool Frequency Treatment phase: n=45	91.1 percentage of patients Interval 78.8 to 97.5

SECONDARY outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. Here "n" signifies patients who were evaluable for each specified category.

Normal consistency of stool was defined as hard and formed or soft and formed consistency. Abnormal consistency was defined as loose and unformed stool or liquid stools and diarrhea. Percentage of stools with normal consistency of each patient was calculated from normal consistency of stools by the patient per day. Mean percentage of stools with normal consistency in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Percentage of Stools With Normal Consistency Baseline phase (usual pancreatic enzymes): n=49	77.38 percentage of stools Standard Deviation 24.274
Percentage of Stools With Normal Consistency Treatment phase: n=45	76.03 percentage of stools Standard Deviation 23.161

SECONDARY outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. Here "n" signifies patients who were evaluable for each specified category.

Stools of abnormal characteristics were defined as bulky/large, foul-smelling and/or oily stools. Mean percentage of stools with abnormal characteristics in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Percentage of Stools With Abnormal Characteristics Baseline phase (usual pancreatic enzymes): n=49	70.37 percentage of stools Standard Deviation 30.037
Percentage of Stools With Abnormal Characteristics Treatment phase: n=45	61.13 percentage of stools Standard Deviation 33.582

SECONDARY outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. Here "n" signifies patients who were evaluable for each specified category.

Abdominal complaints were defined as the reporting of abdominal pain and/or unusual and excessive flatulence/gas production. Mean number of days without abdominal complaints in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Mean Number of Days Without Abdominal Complaints Baseline phase (usual pancreatic enzymes): n=49	2.0 days Standard Deviation 1.89
Mean Number of Days Without Abdominal Complaints Treatment phase: n=45	2.3 days Standard Deviation 2.08

OTHER_PRE_SPECIFIED outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. Here "N" (number of patients analyzed) represents number of patients who were evaluable for this outcome measure. Here "n" signifies patients who were evaluable for each specified category.

The total weight of stools in grams (g) is the total weight obtained during the stool collection period regardless of the number of stools that had been collected during this same collection period. Mean total weight of stools in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.

Outcome measures

Measure	Ultrase® MT12 n=48 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Total Weight of Stools Baseline phase (usual pancreatic enzymes): n=48	349.2 gram (g) Standard Deviation 144.40
Total Weight of Stools Treatment phase: n=45	367.0 gram (g) Standard Deviation 155.85

OTHER_PRE_SPECIFIED outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. Here "n" signifies patients who were evaluable for each specific category.

Mean percentage of days with abdominal complaints during baseline phase (BP) and the 5-day collection period of the treatment phase for total patients was summarized. Abdominal complaints were defined as the reporting of abdominal pain and/or unusual and excessive flatulence/gas production. Mean number of days abdominal pain (AP) and excessive flatulence (EF) in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Percentage of Days With Abdominal Pain and Excessive Flatulence BP (usual pancreatic enzymes): AP (n=48)	12.50 percentage of days Standard Deviation 27.250
Percentage of Days With Abdominal Pain and Excessive Flatulence Treatment phase: AP (n=44)	9.20 percentage of days Standard Deviation 20.056
Percentage of Days With Abdominal Pain and Excessive Flatulence BP (usual pancreatic enzymes): EF (n=49)	52.04 percentage of days Standard Deviation 37.582
Percentage of Days With Abdominal Pain and Excessive Flatulence Treatment phase: EF (n=45)	45.56 percentage of days Standard Deviation 42.080

POST_HOC outcome

Timeframe: A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Population: The ITT population included all patients who signed an ICF and started the baseline phase. There was no imputation of missing data. Here "n" signifies patients who were evaluable for each specific category.

Control of steatorrhea was defined as a less than 30 percent (%) of fat in stools as measured by nuclear magnetic resonance (NMR) spectroscopy in all stool samples which are collected in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12.

Outcome measures

Measure	Ultrase® MT12 n=49 Participants Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Percentage of Patients With Control of Steatorrhea Based on Concomitant Use of Proton Pump Inhibitors (PPIs) BP (usual pancreatic enzymes): With PPIs (n=28)	53.6 percentage of patients Interval 33.9 to 72.5
Percentage of Patients With Control of Steatorrhea Based on Concomitant Use of Proton Pump Inhibitors (PPIs) Treatment phase: With PPIs (n=26)	53.8 percentage of patients Interval 33.4 to 73.4
Percentage of Patients With Control of Steatorrhea Based on Concomitant Use of Proton Pump Inhibitors (PPIs) BP (usual pancreatic enzymes): Without PPIs(n=20)	40.0 percentage of patients Interval 19.1 to 64.0
Percentage of Patients With Control of Steatorrhea Based on Concomitant Use of Proton Pump Inhibitors (PPIs) Treatment phase: Without PPIs (n=19)	36.8 percentage of patients Interval 16.3 to 61.6

Adverse Events

Ultrase® MT12

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ultrase® MT12 n=48 participants at risk Ultrase® MT12 capsules were given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose was not to exceed 10,000 lipase units/kg/day.
Gastrointestinal disorders Abdominal pain	4.2% 2/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Gastrointestinal disorders Abdominal pain upper	4.2% 2/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Gastrointestinal disorders Constipation	6.2% 3/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Gastrointestinal disorders Diarrhoea	4.2% 2/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Gastrointestinal disorders Vomiting	8.3% 4/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
General disorders Pyrexia	8.3% 4/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Investigations Feacal fat increased	4.2% 2/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Metabolism and nutrition disorders Decreased appetite	4.2% 2/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 5/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 4/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.2% 2/48 • From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit) Safety population included patients who signed an ICF, completed the baseline phase and started the treatment phase by taking at least one dose of the study treatment. Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication.

Additional Information

Robert Winkler, MD, VP, Clinical Development and Operations

Aptalis Pharma US, Inc.

Phone: 1- 800- 472- 263

Results disclosure agreements

• Principal investigator is a sponsor employee Restrictions vary in accordance with each agreement with the individual investigators. Sponsor will allow publication after a multi-center publication has been published or after an agreed period of time if no such multi-center publication is submitted for publication. Sponsor can ask that Sponsor's confidential information be removed from 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