A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age

• ClinicalTrials.gov Identifier: NCT01100606
• Recruitment Status: Completed
• First Posted: April 9, 2010
• Results First Posted: April 10, 2014
• Last Update Posted: April 10, 2014
• Sponsor: Forest Laboratories
• Information provided by (Responsible Party): Forest Laboratories

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Cystic Fibrosis; Exocrine Pancreatic Insufficiency
• Intervention: Drug: EUR-1008 (APT-1008)
• Enrollment: 15

Participant Flow

Recruitment Details
Pre-assignment Details	All enrolled participants were administered Zenpep® 5,000 (pancrelipase) from open capsule mixed with a small amount of apple sauce in the screening period for 10 days.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice First, Then in Apple Sauce	EUR-1008 (APT-1008) in Apple Sauce First, Then in Apple Juice
Arm/Group Description	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in first treatment period followed by EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in second treatment period. Total dose was not to exceed 10,000 lipase units/kilogram body weight/day (lipase units/kg/day).	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in first treatment period followed by EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in second treatment period. Total dose was not to exceed 10,000 lipase units/kg/day.
Period Title: First Treatment Period
Started	8	7
Completed	8 [1]	7
Not Completed	0	0
[1] Due to difficulty with syringe nurser,1 participant completed study with apple sauce,not apple juice
Period Title: Second Treatment Period
Started	8	7
Completed	8 [1]	7 [2]
Not Completed	0	0
[1] Due to intolerance to apple sauce & apple juice,1 participant completed study with banana-based food; [2] Due to difficulty with syringe nurser, 1 participant completed study using apple sauce

Baseline Characteristics

Arm/Group Title		Entire Study Population
Arm/Group Description		Includes all enrolled participants who received EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) mixed with a small amount of apple juice using a syringe nurser first and EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) mixed with a small amount of apple sauce using a spoon first.
Overall Number of Baseline Participants		15
Baseline Analysis Population Description		Safety analysis population included all participants who received at least 1 dose of study medication.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	15 participants
		5.7 (3.15)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	Female	6 40.0%
	Male	9 60.0%
Average Daily Number of Stools [1]; Mean (Standard Deviation); Unit of measure: Average number of stools per day
	Number Analyzed	15 participants
		2.73 (1.393)
		[1] Measure Description: Average daily number of stools of each participant was calculated from frequency of stools by the participant per day. Average daily number of stools during the screening period for total participants was summarized. Number of participants evaluable for this baseline characteristic was 12.
Number of Stools Categorized as Per Consistency [1]; Mean (Standard Deviation); Unit of measure: Average number of stools per day	Number Analyzed	15 participants
Hard		0.11 (0.255)
Normal		1.18 (1.129)
Soft		0.91 (0.777)
Diarrhea		0.48 (0.801)
		[1] Measure Description: Stool consistency was categorized as hard, formed/normal, soft and diarrhea. Average number of stools categorized as per consistency of each participant was calculated from number of stools of specific consistency by the participant per day. Average number of stools categorized as per consistency during the screening period for total participants was summarized. Number of participants evaluable for this baseline characteristic was 12.
Number of Stools With Signs of Blood and Visible Oil or Grease [1]; Mean (Standard Deviation); Unit of measure: Average number of stools per day	Number Analyzed	15 participants
With blood		0 (0)
With visible oil or grease		0.11 (0.147)
		[1] Measure Description: Average number of stools with signs of blood and visible oil or grease of each participant was calculated from number of stools with signs of blood and visible oil or grease by the participant per day. Average number of stools stools with signs of blood and visible oil or grease during the screening period for total participants was summarized. Number of participants evaluable for this baseline characteristic was 12.
Number of Abdominal Symptoms: Bloating [1]; Mean (Standard Deviation); Unit of measure: Average number of bloating per day	Number Analyzed	15 participants
Mild Bloating		0.12 (0.281)
Moderate Bloating		0.04 (0.101)
Severe Bloating		0 (0)
		[1] Measure Description: Bloating is swelling of the intestinal tract caused by excessive gas formation. Symptoms of bloating were classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the screening period for total participants was summarized. Number of participants evaluable for this baseline characteristic was 12.
Number of Abdominal Symptoms: Flatulence [1]; Mean (Standard Deviation); Unit of measure: Average number of flatulence per day	Number Analyzed	15 participants
Mild Flatulence		1.00 (1.208)
Moderate Flatulence		0.51 (0.728)
Severe Flatulence		0.03 (0.099)
		[1] Measure Description: Flatulence is presence of excessive gas in the digestive tract. Symptoms of flatulence were classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the screening period for total participants was summarized. Number of participants evaluable for this baseline characteristic was 12.
Number of Abdominal Pain Symptoms [1]; Mean (Standard Deviation); Unit of measure: Average number of pain symptoms per day	Number Analyzed	15 participants
Mild Abdominal Pain		0.23 (0.409)
Moderate Abdominal Pain		0.09 (0.185)
Severe Abdominal Pain		0.02 (0.066)
		[1] Measure Description: Symptoms of pain was classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the screening period for total participants was summarized. Number of participants evaluable for this baseline characteristic was 12.

Outcome Measures

1. Primary Outcome

Title	Treatment Difference for Acceptability of Treatment
Description	Acceptability questionnaire consists of 9 question (Q) to assess ease, time, overall satisfaction of study drug. Rated on 5-point scale for Q1-Q5 and Q7-Q9; Q6 was not rated and asked for name of previous PEP administered. Q1=overall ease of administration (1=not at all easy,2=somewhat,3=easy,4=very,5=extremely); Q2=time of administration (1=very short[<2 min],2=short[2-5 min],3=moderate[5-15 min],4=long[15-25 min],5=very long[>25 min]);Q3=overall infant acceptance(1=very easily,2=easily,3=same,4=with difficulty,5=with great difficulty);Q4=clear/complete instructions(1=not clear,2=somewhat,3=clear,4=very,5=extremely);Q5=overall satisfaction with dosing method (1=not satisfied,2=somewhat,3=satisfied,4=very,5=extremely);Q7=comparative ease of administration (1=much worse,2=worse,3=same,4=better,5=much better);Q8=comparative infant acceptance (1=much more difficult,2=more,3=same,4=easier,5=much easier);Q9=comparative overall satisfaction (1=much less,2=less,3=same,4=more,5=much more).
Time Frame	Baseline up to end of study (Day 21)

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of exocrine pancreatic insufficiency (EPI). Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsules) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily with dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsules) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily with dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Median (Full Range); Unit of Measure: units on a scale
Ease of Administration	1.5; (1 to 3)	3.5; (2 to 5)
Time of Administration	2.5; (1 to 4)	1.0; (1 to 3)
Overall Infant Acceptance	3.5; (2 to 5)	1.5; (1 to 4)
Dispensing Instructions	3.0; (1 to 5)	4.5; (3 to 5)
Overall Satisfaction	1.0; (1 to 3)	3.0; (2 to 4)
Comparative Ease of Administration	2.0; (1 to 5)	3.0; (2 to 5)
Comparative Infant Acceptance	2.0; (1 to 5)	3.0; (3 to 5)
Comparative Overall Satisfaction	1.0; (1 to 4)	3.0; (3 to 5)

2. Primary Outcome

Title	Question 6 (Previous Pancreatic Enzyme Product [PEP])
Description	Acceptability questionnaire consists of 9 questions (Q) to assess the ease, time, overall satisfaction of study drug. Q6 included "name of previous PEP administered". Q6 was reported as number of participants who used any PEP prior to screening.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Safety analysis population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Entire Study Population
Arm/Group Description:	Includes all enrolled participants who received EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) mixed with a small amount of apple juice using a syringe nurser first and EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) mixed with a small amount of apple sauce using a spoon first.
Overall Number of Participants Analyzed	15
Measure Type: Number; Unit of Measure: participants
Zenpep®	4
Creon®	9
Ultrase®	1
Pancrecarb®	1

3. Secondary Outcome

Title	Daily Number of Stools
Description	Average daily number of stools of each participant was calculated from frequency of stools by the participant per day. Average daily number of stools during the first treatment period, second treatment period and end of study for total participants was summarized.
Time Frame	Up to Day 10 in first and second treatment periods, end of study (Day 21)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire on and clinical signs and symptoms of EPI. Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: average number of stools per day
	2.76 (0.771)	2.44 (0.766)

4. Secondary Outcome

Title	Number of Stools Categorized as Per Consistency
Description	Stool consistency was categorized as hard, formed/normal, soft and diarrhea. Average number of stools categorized as per consistency of each participant was calculated from number of stools of specific consistency by the participant per day. Average number of stools categorized as per consistency during the first treatment period, second treatment period and end of study for total participants was summarized.
Time Frame	Up to Day 10 in first and second treatment periods, end of study (Day 21)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of EPI. Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: average number of stools per day
Hard	0.04 (0.089)	0.14 (0.184)
Normal	1.77 (0.864)	1.37 (0.770)
Soft	0.62 (0.710)	0.83 (0.813)
Diarrhea	0.24 (0.527)	0.07 (0.135)

5. Secondary Outcome

Title	Number of Stools With Signs of Blood and Visible Oil or Grease
Description	Average number of stools with signs of blood and visible oil or grease of each participant was calculated from number of stools with signs of blood and visible oil or grease by the participant per day. Average number of stools with signs of blood and visible oil or grease during the first treatment period, second treatment period and end of study for total participants was summarized.
Time Frame	Up to Day 10 in first and second treatment periods, end of study (Day 21)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of EPI. Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: average number of stools per day
With blood	0 (0)	0.01 (0.047)
With visible oil or grease	0.09 (0.191)	0.17 (0.368)

6. Secondary Outcome

Title	Number of Abdominal Symptoms: Bloating
Description	Bloating is swelling of the intestinal tract caused by excessive gas formation. Symptoms of bloating were classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the first treatment period, second treatment period and end of study for total participants was summarized.
Time Frame	Up to Day 10 in first and second treatment periods, end of study (Day 21)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of EPI. Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: average number of bloating per day
Mild Bloating	0.22 (0.632)	0.26 (0.857)
Moderate Bloating	0 (0)	0 (0)
Severe Bloating	0 (0)	0 (0)

7. Secondary Outcome

Title	Number of Abdominal Symptoms: Flatulence
Description	Flatulence is presence of excessive gas in the digestive tract. Symptoms of flatulence were classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the first treatment period, second treatment period and end of study for total participants was summarized.
Time Frame	Up to Day 10 in first and second treatment periods, end of study (Day 21)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of EPI. Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: average number of flatulence per day
Mild Flatulence	1.0 (1.583)	0.62 (0.869)
Moderate Flatulence	0.31 (0.559)	0.32 (0.670)
Severe Flatulence	0.04 (0.144)	0 (0)

8. Secondary Outcome

Title	Number of Abdominal Pain Symptoms
Description	Symptoms of pain was classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the first treatment period, second treatment period and end of study for total participants was summarized.
Time Frame	Up to Day 10 in first and second treatment periods, end of study (Day 21)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of EPI. Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: average number of pain symptoms per day
Mild Abdominal Pain	0.10 (0.259)	0.13 (0.343)
Moderate Abdominal Pain	0.09 (0.238)	0.07 (0.231)
Severe Abdominal Pain	0 (0)	0 (0)

9. Secondary Outcome

Title	Number of Participants With Abnormal Clinical Laboratory and Vital Signs Findings
Description	[Not Specified]
Time Frame	Baseline up to end of study (Day 21)

Outcome Measure Data

Analysis Population Description

Data was reported in individual participant listings but not statistically summarized for analysis as planned.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

10. Secondary Outcome

Title	Number of Participants With Abnormal Findings With Respect to Oral Mucosa
Description	Safety assessed by the presence of lesions observed during a physical examination at each visit. Severity of lesions measured by investigator's assessment using the following scale: mild = asymptomatic or mild symptoms and treatment not indicated; moderate = moderate pain but not interfering with oral intake, modified diet indicated; severe = severe pain, interfering with oral intake and life threatening or fatal.
Time Frame	Baseline up to end of study (Day 21)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description:	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
Overall Number of Participants Analyzed	12	15
Measure Type: Number; Unit of Measure: participants
	0	0

Adverse Events

Time Frame	Baseline up to end of study (Day 21)
Adverse Event Reporting Description	Adverse event (AE): any untoward medical occurrence regardless of causal relationship to study drug. Serious AE: any event resulting in death, life threatening, required or prolonged in-patient hospitalization, significant disability/incapacity, or was congenital anomaly/birth defect. Participants at risk in EUR-1008 (APT-1008) in Apple Juice: 12
Arm/Group Title	Zenpep®	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
Arm/Group Description	Zenpep® 5,000 from open capsule, mixed with a small amount of apple sauce, orally daily in the screening period for 10 days.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice using a syringe nurser, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce using a spoon, orally daily at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period.
All-Cause Mortality
	Zenpep®	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Zenpep®	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/12 (0.00%)	0/15 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Zenpep®	EUR-1008 (APT-1008) in Apple Juice	EUR-1008 (APT-1008) in Apple Sauce
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	11/15 (73.33%)	10/12 (83.33%)	14/15 (93.33%)
Blood and lymphatic system disorders
Lymphadenopathy * 1	1/15 (6.67%)	0/12 (0.00%)	1/15 (6.67%)
Congenital, familial and genetic disorders
Cystic fibrosis lung * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Ear and labyrinth disorders
Cerumen impaction * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Gastrointestinal disorders
Flatulence * 1	6/15 (40.00%)	1/12 (8.33%)	5/15 (33.33%)
Abdominal pain * 1	4/15 (26.67%)	3/12 (25.00%)	4/15 (26.67%)
Abdominal distension * 1	2/15 (13.33%)	3/12 (25.00%)	2/15 (13.33%)
Diarrhoea * 1	3/15 (20.00%)	2/12 (16.67%)	1/15 (6.67%)
Steatorrhoea * 1	3/15 (20.00%)	2/12 (16.67%)	4/15 (26.67%)
Teething * 1	2/15 (13.33%)	1/12 (8.33%)	1/15 (6.67%)
Constipation * 1	0/15 (0.00%)	0/12 (0.00%)	2/15 (13.33%)
Faeces hard * 1	0/15 (0.00%)	0/12 (0.00%)	2/15 (13.33%)
Frequent bowel movements * 1	1/15 (6.67%)	0/12 (0.00%)	1/15 (6.67%)
Haematochezia * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Infantile spitting up * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Vomiting * 1	2/15 (13.33%)	0/12 (0.00%)	0/15 (0.00%)
Gastrooesophageal reflux disease * 1	1/15 (6.67%)	0/12 (0.00%)	0/15 (0.00%)
General disorders
Pyrexia * 1	1/15 (6.67%)	2/12 (16.67%)	3/15 (20.00%)
Infections and infestations
Nasopharyngitis * 1	1/15 (6.67%)	0/12 (0.00%)	1/15 (6.67%)
Otitis media * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Upper respiratory tract infection * 1	1/15 (6.67%)	0/12 (0.00%)	1/15 (6.67%)
Pseudomonas infection * 1	1/15 (6.67%)	0/12 (0.00%)	0/15 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Nervous system disorders
Drooling * 1	0/15 (0.00%)	1/12 (8.33%)	0/15 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	1/15 (6.67%)	2/12 (16.67%)	6/15 (40.00%)
Nasal congestion * 1	1/15 (6.67%)	1/12 (8.33%)	1/15 (6.67%)
Rhinorrhoea * 1	1/15 (6.67%)	0/12 (0.00%)	2/15 (13.33%)
Epistaxis * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Stridor * 1	0/15 (0.00%)	0/12 (0.00%)	1/15 (6.67%)
Respiratory tract congestion * 1	1/15 (6.67%)	0/12 (0.00%)	0/15 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (13.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Robert Winkler, MD, VP, Clinical Development and Operations
• Organization: Aptalis Pharma US, Inc.
• Phone: 1-800-472-2634

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01100606
• Other Study ID Numbers: PR-011
• First Submitted: March 31, 2010
• First Posted: April 9, 2010
• Results First Submitted: March 5, 2014
• Results First Posted: April 10, 2014
• Last Update Posted: April 10, 2014