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

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00880100
• Collaborator: (none)
• Enrollment: 49
• Locations: 15
• Arm: 1
• Duration (Months): 7
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Multicenter, explorative, phase IIIb, open-label study to assess the efficacy and safety of Ultrase® MT12, in the control of steatorrhea and clinical signs and symptoms of malabsorption in CF children with pancreatic insufficiency (PI). This study is sponsored by Aptalis Pharma (formerly Axcan).

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Pancreatic Insufficiency	Drug: Ultrase® MT12	Phase 3

Detailed Description

This is a multicenter, explorative, phase IIIb, open-label study in patients with CF and PI. The study consists of a screening visit (visit 1), followed by a baseline phase of 9 days (plus a 5-day window if necessary) during which the regular pancreatic enzyme will be maintained and 10 stool samples will be collected over 5 days, for baseline evaluation of steatorrhea. Afterward, a treatment phase of 19 days (plus a 5-day window if necessary) with Ultrase® MT12 will follow (the usual pancreatic enzyme will be replaced by Ultrase® MT12). Over the last 5 days of the treatment phase, 10 additional stool samples will be collected, for evaluation of steatorrhea.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Ultrase MT12 in the Control of Steatorrhea in Cystic Fibrosis (CF) and Pancreatic Insufficient (PI) Children Aged 2 to 6 Years Old
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ultrase® MT12	Drug: Ultrase® MT12; Ultrase® MT12 capsules will be 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 not to exceed 10,000 lipase units/kg/day.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Control of Steatorrhea [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

Secondary Outcome Measures

1. Percentage of Patients With Normal Stool Frequency [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

2. Percentage of Stools With Normal Consistency [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

3. Percentage of Stools With Abnormal Characteristics [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

4. Mean Number of Days Without Abdominal Complaints [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

Other Outcome Measures

1. Total Weight of Stools [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

2. Percentage of Days With Abdominal Pain and Excessive Flatulence [A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 6 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients aged 2 to 6 years inclusively

• Patients with current diagnosis of CF based on one or more typical clinical features of CF or a sibling with CF or a positive newborn screening and at least either with sweat chloride test greater than or equal to 60 millimoles/liter (mmol/L) by quantitative pilocarpine iontophoresis on two separate occasions or two identifiable CF-causing mutations

• Patients with presence of PI as demonstrated by fecal elastase (FE-1) less than 100 microgram/gram (mcg/g) of stools (performed by ScheBo test) and requiring pancreatic enzyme supplementation

• Patients who are able to eat a high-fat diet calculated at a value between 2g to 4g fat/kg of body weight per day during the whole study and having a current adequate nutritional status based on the body mass index (BMI) greater than or equal to fifth percentile

• Patients receiving current treatment of PI with pancreatic enzymes

• The parent or legal guardian signed informed consent form (ICF) and is mentally able to understand and comply with the study procedures

Exclusion Criteria:

• Patients currently receiving or received an Ultrase® MT product (MT12, MT18, MT20) for PI in the last 30 days

• Patients having known contraindication, sensitivity or hypersensitivity to Ultrase® or to any porcine protein

• Patients with presence of a medical condition known to increase fecal fat loss or that could compromise study results or the study patient safety

• Patients with current diagnosis or history of complete distal intestinal obstruction syndrome (DIOS) in the past 6 months or who had 2 or more episodes of incomplete DIOS in the past year

• Patients with use of any prohibited medication or product at study entry and during the course of the study

• Patients with chronic use of narcotics

• Patients with use of bowel stimulants and/or laxatives more than once a week

• Patients with presence of acute pancreatitis or exacerbation of chronic pancreatic disease

• Patients with presence of an acute infection that needed to be treated with oral or intravenous (IV) broad-spectrum antibiotics

• Patients having history of significant bowel resection; small bowel resection for meconium ileus at birth and appendectomy were accepted. Patients with Presence of dysmotility disorders

• Patients with presence of chronic or severe abdominal pain

• Patients unable to comply with diet requirement

• Patients receiving enteral tube feeding overnight at study entry or who will need to receive enteral tube feeding overnight during the course of the study

• Patients with history of or a current diagnosis of clinically significant portal hypertension

• Patients with presence of poorly controlled diabetes according to the Investigator's clinical judgment

• Patients having any condition or pre-study laboratory abnormality or history of any illness which, in the opinion of the Investigator, might have put the patient at risk, prevented the patient from completing the study, or otherwise affect the outcome of the study

• Patient with use of any investigational drug within 30 days prior to the date of signature of the ICF

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital	Aurora	Colorado	United States	80045
2	University of Michigan Health System Cystic Fibrosis Center	Ann Arbor	Michigan	United States	48109-0212
3	Helen DeVos Children's Hospital-Spectrum Health Research Department	Grand Rapids	Michigan	United States	40503
4	SUNY Upstate Medical University	Syracuse	New York	United States	13203
5	Duke University Medical Center	Durham	North Carolina	United States	27710
6	Rainbow Babies and Children's Hospital - Cystic Fibrosis Center	Cleveland	Ohio	United States	44106
7	Children's Medical Center of Dayton	Dayton	Ohio	United States	45404
8	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
9	Respiratory Diseases of Children and Adolescents	Oklahoma City	Oklahoma	United States	73112
10	Pennsylvania State University and the Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
11	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15213
12	Sanford Children's Specialty Clinic	Sioux Falls	South Dakota	United States	57117-5039
13	University of Utah	Salt Lake City	Utah	United States	84108
14	Virginia Commonwealth University	Richmond	Virginia	United States	23298
15	UW Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Aptalis Medical Information, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00880100
• Other Study ID Numbers: UMT12CF08-01
• First Posted: Apr 13, 2009
• Last Update Posted: Mar 16, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Forest Laboratories: Steatorrhea; Malabsorption of fat; Pancreatic enzymes; Abdominal pain; Greasy stools
• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis; Pancrelipase; Pancreatin

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Period Title: Baseline Phase-Usual Pancreatic Enzymes
STARTED	49
COMPLETED	48
NOT COMPLETED	1
Period Title: Baseline Phase-Usual Pancreatic Enzymes
STARTED	48
COMPLETED	45
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Overall Participants	48
Age (Count of Participants)
<=18 years	48 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.8 (1.42)
Sex: Female, Male (Count of Participants)
Female	19 39.6%
Male	29 60.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Control of Steatorrhea
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
Baseline phase (usual pancreatic enzymes)	46.9
Treatment phase	42.9

2. Secondary Outcome

Title	Percentage of Patients With Normal Stool Frequency
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
Baseline phase (usual pancreatic enzymes): n=49	87.8
Treatment phase: n=45	91.1

3. Secondary Outcome

Title	Percentage of Stools With Normal Consistency
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
Baseline phase (usual pancreatic enzymes): n=49	77.38 (24.274)
Treatment phase: n=45	76.03 (23.161)

4. Secondary Outcome

Title	Percentage of Stools With Abnormal Characteristics
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
Baseline phase (usual pancreatic enzymes): n=49	70.37 (30.037)
Treatment phase: n=45	61.13 (33.582)

5. Secondary Outcome

Title	Mean Number of Days Without Abdominal Complaints
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
Baseline phase (usual pancreatic enzymes): n=49	2.0 (1.89)
Treatment phase: n=45	2.3 (2.08)

6. Other Pre-specified Outcome

Title	Total Weight of Stools
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	48
Baseline phase (usual pancreatic enzymes): n=48	349.2 (144.40)
Treatment phase: n=45	367.0 (155.85)

7. Other Pre-specified Outcome

Title	Percentage of Days With Abdominal Pain and Excessive Flatulence
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
BP (usual pancreatic enzymes): AP (n=48)	12.50 (27.250)
Treatment phase: AP (n=44)	9.20 (20.056)
BP (usual pancreatic enzymes): EF (n=49)	52.04 (37.582)
Treatment phase: EF (n=45)	45.56 (42.080)

8. Post-Hoc Outcome

Title	Percentage of Patients With Control of Steatorrhea Based on Concomitant Use of Proton Pump Inhibitors (PPIs)
Description	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.
Time Frame	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
Measure Participants	49
BP (usual pancreatic enzymes): With PPIs (n=28)	53.6
Treatment phase: With PPIs (n=26)	53.8
BP (usual pancreatic enzymes): Without PPIs(n=20)	40.0
Treatment phase: Without PPIs (n=19)	36.8

Adverse Events

Time Frame	From signing of informed consent up to the study discharge (last study visit on Day 24 of treatment phase or early discontinuation visit)
Adverse Event Reporting Description	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.
Arm/Group Title	Ultrase® MT12
Arm/Group Description	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.
All Cause Mortality
	Ultrase® MT12
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ultrase® MT12
	Affected / at Risk (%)	# Events
Total	0/48 (0%)
Other (Not Including Serious) Adverse Events
	Ultrase® MT12
	Affected / at Risk (%)	# Events
Total	24/48 (50%)
Gastrointestinal disorders
Abdominal pain	2/48 (4.2%)
Abdominal pain upper	2/48 (4.2%)
Constipation	3/48 (6.3%)
Diarrhoea	2/48 (4.2%)
Vomiting	4/48 (8.3%)
General disorders
Pyrexia	4/48 (8.3%)
Investigations
Feacal fat increased	2/48 (4.2%)
Metabolism and nutrition disorders
Decreased appetite	2/48 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	5/48 (10.4%)
Nasal congestion	4/48 (8.3%)
Rhinorrhoea	2/48 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.