Study of Pancreatic Enzyme Product in Pediatric Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00981214
• Collaborator: (none)
• Enrollment: 19
• Locations: 14
• Arm: 1
• Duration (Months): 4
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is an open-label study to evaluate the efficacy and safety of Aptalis' (formerly Eurand) pancreatic enzyme product (PEP) microtabs in pediatric participants under age 7 with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI).

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Exocrine Pancreatic Insufficiency	Drug: EUR-1008 (APT-1008)	Phase 3

Detailed Description

The study sample will consist of evaluable participants, all of whom will be children younger than 7 years of age. Participants will receive EUR-1008 (APT-1008) Microtabs formulation. The study design involves a 4-day screening period, a 7-day dose stabilization period, and a 7-day treatment period (excluding an end-of-study evaluation).

The optimal dose of EUR-1008 (APT-1008) Microtabs, determined during the dose stabilization period, will be used during the treatment period. Participants are instructed to consume a predefined diet.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Efficacy and Safety of Pancreatic Enzyme Product (PEP) Microtabs in Pediatric Patients With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Sep 1, 2006
• Actual Study Completion Date: Sep 1, 2006

Arms and Interventions

Arm

Intervention/Treatment

Experimental: EUR-1008 (APT-1008)

Drug: EUR-1008 (APT-1008); EUR-1008 (APT-1008) Microtabs contained in a capsule will be administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule will be allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).; Other Names: ZENPEP® Pancrelipase

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Were Responders After 1 Week of Treatment With Study Medication [Day 11]

   Responders were defined as those participants without steatorrhea (defined as less than 30 percent (%) fecal fat content) and without signs and symptoms of malabsorption after 1 week of treatment with study medication.

2. Percentage of Participants Who Were Responders After 2 Weeks of Treatment With Study Medication [Day 18 (end of treatment)]

   Responders were defined as those participants without steatorrhea (defined as less than 30% fecal fat content) and without signs and symptoms of malabsorption after 2 weeks of treatment with study medication.

Secondary Outcome Measures

1. Change From Baseline in Weight at Day 12, 19 [Baseline, Day 12, 19]

2. Mean Daily Number of Stools [Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)]

   Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools at each period for total participants was summarized.

3. Percentage of Stool Categorized by Consistency [Baseline, Day 5 up to Day 11 (dose stabilization period) and Day 12 up to Day 18 (treatment period)]

   Stool consistency was categorized as hard, formed/normal, soft, watery or overt diarrhea. Percentage of stools of a specific consistency of each participant was calculated as the number of stools with a specific consistency relative to the total number of stools during the collection period. Mean percentage of stool with specific consistency at each period for total participants was summarized.

4. Mean Number of Abdominal Symptoms: Bloating [Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)]

   Bloating is swelling of the intestinal tract caused by excessive gas formation. Symptoms of bloating were classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.

5. Mean Number of Abdominal Symptoms: Flatulence [Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)]

   Flatulence is presence of excessive gas in the digestive tract. Symptoms of flatulence was classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.

6. Mean Number of Pain Symptoms [Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)]

   Symptoms of pain was classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.

7. Physician's and Parent's or Legal Guardians Assessment of Improvement in Clinical Symptoms [Day 19 (end of study)]

   Clinical symptoms of exocrine pancreatic insufficiency (EPI) were assessed by the physician and parent or guardian to determine if the participant showed improvement in symptoms of EPI at end of study after the dose stabilization period. EPI is a syndrome characterized by clinical symptoms of poor absorption of fats, proteins, and to a lesser extent, carbohydrates, which manifests primarily in patients with cystic fibrosis. Number of participants with improvement in clinical symptoms was reported.

8. Percentage of Blood in Stool [Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)]

   Mean percentage of stools with blood at each period for total participants was summarized.

9. Percentage of Stool With Visible Oil or Grease [Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)]

   Mean percentage of oil or grease at each period for total participants was summarized.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 7 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants less than 7 years of age

• Participants who have pancreatic insufficiency documented by a fecal elastase level less than 100 micrograms per gram (mcg/g), or if not documented, the fecal elastase test must be done at the screening visit

• Participants who have a need of de novo treatment with pancreatic enzymes or be able to be switched from an existing treatment

• Participants who have a body mass index greater than the twenty fifth percentile for children 2 years and older

• Participants with a weight for height index greater than the twenty fifth percentile for children less than 2 years of age

• Participants with diagnosis of CF based upon the following criteria:

• Have 2 clinical features consistent with CF and

• Have either a genotype with 2 identifiable mutations consistent with CF or a sweat chloride concentration that is more than 60 milliequivalent per liter (mEq/L) by quantitative pilocarpine iontophoresis

• Participants who are clinically stable with no evidence of acute upper or lower respiratory tract infection

Exclusion Criteria:

• Participants with fibrosing colonopathy

• Participants allergic to pork or other porcine PEPs

• Participants with any respiratory condition that in the investigator's opinion would result in an intervention requiring hospitalization or intensive pulmonary treatment during the trial

• Participants with any acute systemic administration of an antibiotic for any reason in the previous 4 weeks; however, a low stable dose of an antibiotic (such as azithromycin 250 or 500 milligram [mg] up to 3 times per week) is allowed. Moreover, chronic treatment (that is, daily for at least 1 month) with an inhalatory antibiotic (for example, colistin, tobramycin, or ceftazidime) is allowed

• Participants who have hepatic insufficiency as defined by a history or presence of ascites, or a serum albumin level of less than 3.0 milligram per deciliter (mg/dL), or coagulopathy with an international normalized ratio that is greater than 1.7

• Participants with hyperuricemia or hyperuricosuria

• Participants participating in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to screening visit

• Participants with history of or current screening evaluation of hyperglycemia as defined by an 8-hour fasting serum glucose equivalent to 126 mg/dL or more, or of cystic-fibrosis-related diabetes as determined according to the Cystic Fibrosis

Foundation (CFF) Consensus Conference of January 1999 (Section IX Part II), that is:

• Fasting Blood Glucose (FBG) greater than126 mg/dl (7.0 milli mole [mM]) on two or more occasions

• FBG greater than 126 mg/dl (7 .0 mM) plus casual (without regard to time of day or last meal consumed) glucose level greater than200 mg/dl (11.1 mM)

• Casual (previously called random) glucose levels greater than 200 mg/dl (11.1 mM) on two or more occasions with symptoms

• Participants with any solid organ transplant or surgery affecting the bowel

• Participants using an enzyme preparation in excess of 10,000 lipase units/kg/day

• Participants with an acute dose of any steroid in the previous 2 weeks; however, low chronic doses of a steroid (less 0.5 mg/kg every other day) will be allowed

• Participants with any condition that would, in the investigator's opinion, limit the patient's ability to complete the study

• Participants with history of or current screening determination of distal ileal obstruction syndrome (DIOS), or any clinical signs and symptoms suggestive of DIOS (that is, constipation, abdominal pain, anorexia, early satiety, recurrent vomiting and palpable fecal mass) on physical examination

• Participants who are unable to discontinue excluded concomitant medications over the course of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
3	Children's Hospital - Oakland	Oakland	California	United States	94609
4	Stanford University Medical Center	Palo Alto	California	United States	94304
5	Children's Hospital of San Diego	San Diego	California	United States	92123
6	University of Florida College of Medicine	Gainsville	Florida	United States	32610-0296
7	Nemours Childrens Clinic	Jacksonville	Florida	United States	32250
8	Childrens Memorial Hospital	Chicago	Illinois	United States	60614
9	University of Iowa	Iowa City	Iowa	United States	52242
10	University of Michigan, Cystic Fibrosis Center	Ann Arbor	Michigan	United States	48109
11	Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
12	University of Texas	Tyler	Texas	United States	75708
13	University of Utah	Salt Lake City	Utah	United States	84108
14	West Virginia Health Sciences Center	Morgantown	West Virginia	United States	26506

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: NCT00981214
• Other Study ID Numbers: EUR-1009-M
• First Posted: Sep 22, 2009
• Last Update Posted: Mar 16, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Forest Laboratories: Cystic fibrosis; Exocrine Pancreatic Insufficiency; Zenpep-1009
• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis; Pancrelipase

Study Results

Participant Flow

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.9 (1.58)
Sex: Female, Male (Count of Participants)
Female	7 36.8%
Male	12 63.2%
Percentage of Participants Who Were Responders (percentage of participants) [Number]
Number [percentage of participants]	52.6 276.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Were Responders After 1 Week of Treatment With Study Medication
Description	Responders were defined as those participants without steatorrhea (defined as less than 30 percent (%) fecal fat content) and without signs and symptoms of malabsorption after 1 week of treatment with study medication.
Time Frame	Day 11

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	68.4 360%

2. Secondary Outcome

Title	Change From Baseline in Weight at Day 12, 19
Time Frame	Baseline, Day 12, 19

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Baseline	16.60 (3.843)
Change at Day 12	0.15 (0.401)
Change at Day 19	0.03 (0.529)

3. Secondary Outcome

Title	Mean Daily Number of Stools
Description	Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Baseline	1.82 (0.787)
Dose stabilization period	1.64 (0.722)
Treatment period	1.45 (0.548)

4. Primary Outcome

Title	Percentage of Participants Who Were Responders After 2 Weeks of Treatment With Study Medication
Description	Responders were defined as those participants without steatorrhea (defined as less than 30% fecal fat content) and without signs and symptoms of malabsorption after 2 weeks of treatment with study medication.
Time Frame	Day 18 (end of treatment)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	57.9 304.7%

5. Secondary Outcome

Title	Percentage of Stool Categorized by Consistency
Description	Stool consistency was categorized as hard, formed/normal, soft, watery or overt diarrhea. Percentage of stools of a specific consistency of each participant was calculated as the number of stools with a specific consistency relative to the total number of stools during the collection period. Mean percentage of stool with specific consistency at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period) and Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Hard: Baseline	5.45 (15.782)
Hard: Dose stabilization period	4.59 (12.694)
Hard: Treatment period	3.78 (8.624)
Formed/Normal: Baseline	59.46 (37.956)
Formed/Normal: Dose stabilization period	58.20 (33.675)
Formed/Normal: Treatment period	59.38 (35.671)
Soft: Baseline	30.18 (33.382)
Soft: Dose stabilization period	32.32 (28.283)
Soft: Treatment period	33.15 (31.460)
Watery: Baseline	4.54 (8.339)
Watery: Dose stabilization period	3.03 (6.988)
Watery: Treatment period	3.16 (6.561)
Overt Diarrhea: Baseline	0.38 (1.639)
Overt Diarrhea: Dose stabilization period	1.86 (8.097)
Overt Diarrhea: Treatment period	0.53 (2.294)

6. Secondary Outcome

Title	Mean 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 mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Mild: Baseline	0.11 (0.326)
Mild: Dose stabilization period	0.14 (0.391)
Mild: Treatment period	0.08 (0.230)
Moderate: Baseline	0.06 (0.159)
Moderate: Dose stabilization period	0.02 (0.098)
Moderate: Treatment period	0.01 (0.029)
Severe: Baseline	0.04 (0.172)
Severe: Dose stabilization period	0.00 (0.000)
Severe: Treatment period	0.00 (0.000)

7. Secondary Outcome

Title	Mean Number of Abdominal Symptoms: Flatulence
Description	Flatulence is presence of excessive gas in the digestive tract. Symptoms of flatulence was classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Mild: Baseline	0.13 (0.262)
Mild: Dose stabilization period	0.20 (0.283)
Mild: Treatment period	0.08 (0.215)
Moderate: Baseline	0.06 (0.109)
Moderate: Dose stabilization period	0.06 (0.204)
Moderate: Treatment period	0.00 (0.000)
Severe: Baseline	0.04 (0.119)
Severe: Dose stabilization period	0.02 (0.045)
Severe: Treatment period	0.09 (0.393)

8. Secondary Outcome

Title	Mean Number of Pain Symptoms
Description	Symptoms of pain was classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

Analysis population set included all participants who received at least 1 dose of study.

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Mild: Baseline	0.09 (0.210)
Mild: Dose stabilization period	0.14 (0.321)
Mild: Treatment period	0.07 (0.204)
Moderate: Baseline	0.04 (0.118)
Moderate: Dose stabilization period	0.08 (0.204)
Moderate: Treatment period	0.00 (0.000)
Severe: Baseline	0.00 (0.000)
Severe: Dose stabilization period	0.05 (0.201)
Severe: Treatment period	0.00 (0.000)

9. Secondary Outcome

Title	Physician's and Parent's or Legal Guardians Assessment of Improvement in Clinical Symptoms
Description	Clinical symptoms of exocrine pancreatic insufficiency (EPI) were assessed by the physician and parent or guardian to determine if the participant showed improvement in symptoms of EPI at end of study after the dose stabilization period. EPI is a syndrome characterized by clinical symptoms of poor absorption of fats, proteins, and to a lesser extent, carbohydrates, which manifests primarily in patients with cystic fibrosis. Number of participants with improvement in clinical symptoms was reported.
Time Frame	Day 19 (end of study)

Outcome Measure Data

Analysis Population Description

Analysis population set included all participants who received at least 1 dose of study.

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Physician assessment	7 36.8%
Parent/guardian assessment	9 47.4%

10. Secondary Outcome

Title	Percentage of Blood in Stool
Description	Mean percentage of stools with blood at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

Analysis population set included all participants who received at least 1 dose of study.

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Baseline	0 (0)
Dose stabilization period	0 (0)
Treatment period	0 (0)

11. Secondary Outcome

Title	Percentage of Stool With Visible Oil or Grease
Description	Mean percentage of oil or grease at each period for total participants was summarized.
Time Frame	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in a capsule was administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule was allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Measure Participants	19
Baseline	11.10 (14.433)
Dose stabilization period	8.98 (11.879)
Treatment period	4.73 (7.722)

Adverse Events

Time Frame	Baseline up to Day 19
Adverse Event Reporting Description	Adverse event (AE) was defined as any untoward medical occurrence regardless of causal relationship to study medication. 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.
Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) Microtabs contained in capsule was administered orally or sprinkled on food. When required, from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
All Cause Mortality
	EUR-1008 (APT-1008)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	EUR-1008 (APT-1008)
	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)
Infections and infestations
Upper respiratory tract infection	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	EUR-1008 (APT-1008)
	Affected / at Risk (%)	# Events
Total	13/19 (68.4%)
Blood and lymphatic system disorders
Lymphadenopathy	1/19 (5.3%)
Eye disorders
Lacrimation increased	1/19 (5.3%)
Gastrointestinal disorders
Abdominal discomfort	1/19 (5.3%)
Abdominal distension	1/19 (5.3%)
Abdominal pain	5/19 (26.3%)
Diarrhoea	1/19 (5.3%)
Faeces discoloured	2/19 (10.5%)
Flatulence	2/19 (10.5%)
Steatorrhoea	3/19 (15.8%)
Vomiting	2/19 (10.5%)
General disorders
Pyrexia	3/19 (15.8%)
Infections and infestations
Bronchitis	1/19 (5.3%)
Sinusitis	1/19 (5.3%)
Upper respiratory tract infection	1/19 (5.3%)
Injury, poisoning and procedural complications
Contusion	1/19 (5.3%)
Injury	1/19 (5.3%)
Sunburn	1/19 (5.3%)
Metabolism and nutrition disorders
Anorexia	1/19 (5.3%)
Decreased appetite	1/19 (5.3%)
Nervous system disorders
Headache	1/19 (5.3%)
Psychiatric disorders
Insomnia	1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/19 (5.3%)
Nasal congestion	2/19 (10.5%)
Paranasal sinus hypersecretion	1/19 (5.3%)
Rhinorrhoea	3/19 (15.8%)

Limitations/Caveats

Protocol amendment 4 extended screening period to 14 days, but this period not included in result as all participants started treatment prior to site Institutional Review Board approval of protocol amendment 4, this did not affect study procedures.

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.