Study to Evaluate the Safety and Efficacy of EUR-1008 (AP... | NCT00297167

Label	Type	Description	Intervention Names
EUR-1008 (APT-1008) First, Then Placebo	Experimental		Drug: EUR-1008 (APT-1008) Drug: Placebo
Placebo First, Then EUR-1008 (APT-1008)	Experimental		Drug: Placebo Drug: EUR-1008 (APT-1008)

Name	Type	Description	Arm Group Labels	Other Names
EUR-1008 (APT-1008)	Drug	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule will be given orally daily in first double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for first double-blind intervention period will be 2 days home treatment and 3 to 5 days hospital treatment.

Measure	Description	Time Frame
Percent Coefficient of Fat Absorption (CFA%)	Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)multiplied by 100, determined in the stools collected during the 72-hour hospitalization period. Mean percent CFA was calculated for Day 3 to Day 6 during hospital treatment in first and second double-blind (DB) intervention periods.	Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods

Measure	Description	Time Frame
Percent Coefficient of Nitrogen Absorption (CNA%)	Percent CNA was calculated as ([nitrogen intake-nitrogen excretion]/nitrogen intake)*100, determined in the stools collected during the 72-hour hospitalization period. Nitrogen intake was calculated as protein intake/6.2. Nitrogen excretion was measured as total fecal nitrogen. Mean percent CNA was calculated for Day 3 to Day 6 during hospital treatment in first and second double-blind intervention periods.

Measure	Description	Time Frame
Percentage of Visible Oil or Grease in Stool	Mean percentage of stools with visible oil or grease during the collection period (Day 3 to Day 6 in first and second intervention periods) for total participants was summarized. Percentage was calculated as the number of stools with visible oil or grease divided by the total number of stool per day.	Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants with age greater than or equal to (>=) 7 years at the time of enrollment
Participants with weight 70 kg or less and be in an adequate nutritional status as indicated by a body mass index (BMI) >=20 kg/m^2 for ages 18 and above, or a BMI above the twenty fifth percentile for participants aged 7 to 17 years
Participants with confirmed diagnosis of CF who 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 by quantitative pilocarpine iontophoresis
Participants with confirmed diagnosis of EPI who are currently receiving treatment with a commercially available PEP and have documented with a fecal elastase of <100 microgram per gram stool (if no documentation was available, a stool sample was taken at Screening for determination of fecal elastase).
Clinically stable participants with no evidence of acute respiratory disease or any other acute condition
Participants who are willing and able to interrupt current CF treatment for CF-related malabsorption along with any medications that may affect gastric motility or stomach power of hydrogen (pH)
Participants 18 years of age and older had to a) understand the requirements of the study, b) provide written informed consent, c) agree to abide by the study restrictions, and d) return for the required assessments
Participants 7 to 17 years of age must have a parent(s) or legal guardian who provides written informed consent, agree to abide by the study restrictions
Females participants of childbearing potential must have a negative serum pregnancy test at screening and must agree to use adequate birth control during the study

Exclusion Criteria:

Participants with fibrosing colonopathy, hyperuricemia or hyperuricosuria
Participants who are allergic to pork or other porcine PEPs
Participants with forced expiratory volume (FEV1) <30 percent of predicted FEV1 at screening
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 or chronic treatment with an inhalatory antibiotic is allowed
Participants with hepatic insufficiency as defined by history or presence of ascites or serum albumin level of < 3.0 milligram/deciliter, or a coagulopathy with an international normalized ratio that is greater than 1.7
Participants who have used an acute dose of any steroid in the previous 2 weeks; however, low chronic doses of a steroid is allowed
Participants with history of or current diagnosis of distal ileal obstruction syndrome (DIOS) as evidenced or suggested by constipation, abdominal pain, anorexia, early satiety, recurrent vomiting, and palpable fecal mass on physical examination (the absence of DIOS will be confirmed by an X-ray of the abdomen taken at screening)
Participants with any solid organ transplant or surgery affecting the bowel. Participants with a history of appendectomy and inguinal (non-incarcerated) hernioplasty or meconium ileus without the need for bowel resection could be enrolled. Gastrointestinal-tube-fed patients, in absence of dumping syndrome, were also eligible
Participants with history of or current screening evaluation of hyperglycemia as defined by an 8-hour fasting blood glucose (FBG) of >126 mg/dL, or of CF-related diabetes as determined according to the Cystic Fibrosis Foundation (CFF) Consensus Conference of January 1999 (Section IX Part II), that is: a) FBG >126 mg/dL (7.0 millimoles per liter [mmol/L]) on two or more occasions b)FBG >126 mg/dL (7.0 mmol/L) plus casual (without regard to time of day or last meal consumed) glucose level >200 mg/dL (11.1 mmol/L) c)Casual (previously called random) glucose levels >200 mg/dL (11.1 mmol/L) on two or more occasions with symptoms
Participants using an enzyme preparation in excess of 10,000-lipase units/kg/day
Participants using an immunosuppressive drug
Participants who are expecting an inability to tolerate the washout period and/or the placebo treatment
Participants participating in an investigational study of a drug, biologic, or device not currently approved for marketing, within 30 days of screening visit
Female participants who are pregnant or breastfeeding, or unwilling to use effective birth control during study
Participants with any condition that would, in the investigator's opinion, limit the participant's ability to complete the study

Name	Affiliation	Role
Aptalis Medical Information	Forest Laboratories	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Texas Health Center at Tyler		Tyler	Texas	75708	United States

PubMed Identifier	Type	Citation	Retractions
19683970	Derived	Wooldridge JL, Heubi JE, Amaro-Galvez R, Boas SR, Blake KV, Nasr SZ, Chatfield B, McColley SA, Woo MS, Hardy KA, Kravitz RM, Straforini C, Anelli M, Lee C. EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. J Cyst Fibros. 2009 Dec;8(6):405-17. doi: 10.1016/j.jcf.2009.07.006. Epub 2009 Aug 15.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo First, Then EUR-1008 (APT-1008)	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first double-blind intervention period followed by EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the second double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units per kilogram body weight per day (lipase units/kg/day).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Entire Study Population	Includes participants who received EUR-1008 (APT-1008) in open-label dose titration and stabilization phase; and EUR-1008 (APT-1008) first and placebo first after randomization to study treatment.

Units	Counts
Participants	BG00034

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Coefficient of Fat Absorption (CFA%)

Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)multiplied by 100, determined in the stools collected during the 72-hour hospitalization period. Mean percent CFA was calculated for Day 3 to Day 6 during hospital treatment in first and second double-blind (DB) intervention periods.

Efficacy analysis population included all randomized and treated participants with at least 1 post-baseline measurement for each double-blind intervention period. Here "N" (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Posted

Least Squares Mean

Standard Error

percent CFA

Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Units	Counts
Participants	OG00032 OG00131

Title

Denominators

Categories

Title	Measurements
	OG00088.28± 2.599 OG00162.76± 2.639

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	P-Value was calculated using analysis of variance (ANOVA) model which included main effects for treatment and sequence and participant nested in sequence as a random effect.	ANOVA		<0.001		Least Square (LS) Mean Difference	-25.52			2-Sided	95	-31.73	-19.32					Superiority or Other

Secondary

Percent Coefficient of Nitrogen Absorption (CNA%)

Percent CNA was calculated as ([nitrogen intake-nitrogen excretion]/nitrogen intake)*100, determined in the stools collected during the 72-hour hospitalization period. Nitrogen intake was calculated as protein intake/6.2. Nitrogen excretion was measured as total fecal nitrogen. Mean percent CNA was calculated for Day 3 to Day 6 during hospital treatment in first and second double-blind intervention periods.

Posted

Least Squares Mean

Standard Error

percent CNA

Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001

Secondary

Lipid Levels

Lipid levels were reported for total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) from fasted blood and urine samples. Mean lipid levels for Day 6 during first and second double-blind intervention periods were calculated.

Safety population included all participants who received at least 1 dose of study treatment. Here "N" (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and "n" signifies participants who were evaluable at specific time point in each treatment arm.

Posted

Mean

Standard Deviation

milligram/deciliter (mg/dL)

End of treatment (Day 6 during first and second double-blind intervention periods)

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Secondary

Vitamin A Levels

Mean Vitamin A levels for Day 6 during first and second double-blind intervention periods were calculated.

Posted

Mean

Standard Deviation

microgram per liter (mcg/L)

End of treatment (Day 6 during first and second double-blind intervention periods)

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Secondary

Vitamin E Levels

Mean Vitamin E levels for Day 6 during first and second double-blind intervention periods were calculated.

Posted

Mean

Standard Deviation

mg/L

End of treatment (Day 6 during first and second double-blind intervention periods)

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Secondary

Mean Daily Number of Stools

Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools during the collection period (Day 3 to Day 6 in first and second double-blind intervention periods) for total participants was summarized.

Efficacy analysis population included all randomized and treated participants with at least 1 post-baseline measurement for each double-blind intervention period.

Posted

Mean

Standard Deviation

stools per day

Day 3 up to Day 6 during first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Secondary

Percentage of Stool Categorized as Per Consistency

Stool consistency was categorized as hard, formed/normal, soft, watery, or overt diarrhea. Percentage of stools of a specific consistency for each participant at first and second double-blind intervention periods was calculated. Mean percentage of stool consistency during the collection period (Day 3 to Day 6 in first and second intervention periods) for total participants was summarized.

Efficacy analysis population included all randomized and treated participants with at least 1 post-baseline measurement for each double-blind intervention period.

Posted

Mean

Standard Deviation

percentage of stools

Day 3 up to Day 6 during first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Secondary

Mean Number of Abdominal Symptoms

Abdominal symptoms included abdominal pain, flatulence and bloating. Symptoms 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 symptom of specific severity per day for each participant was calculated. Mean number of symptoms per day was calculated for Day 3 to Day 6 in first and second double-blind intervention periods for total participants.

Efficacy analysis population included all randomized and treated participants with at least 1 post-baseline measurement for each double-blind intervention period.

Posted

Mean

Standard Deviation

symptoms per day

Day 3 up to Day 6 during first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo

Other Pre-specified

Percentage of Visible Oil or Grease in Stool

Mean percentage of stools with visible oil or grease during the collection period (Day 3 to Day 6 in first and second intervention periods) for total participants was summarized. Percentage was calculated as the number of stools with visible oil or grease divided by the total number of stool per day.

Efficacy analysis population included all randomized and treated participants with at least 1 post-baseline measurement for each double-blind intervention period.

Posted

Mean

Standard Deviation

percentage of visible oil or grease/day

Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Other Pre-specified

Percentage of Stools With Blood

Mean percentage of stools with blood during the collection period (Day 3 to Day 6 in first and second intervention periods) for total participants was summarized. Percentage was calculated as the number of stools with blood divided by the total number of stool per day.

Efficacy analysis population included all randomized and treated participants with at least 1 post-baseline measurement for each double-blind intervention period.

Posted

Mean

Standard Deviation

percentage of stools with blood per day

Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods

ID	Title	Description
OG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule and was given orally daily in the first and second double-blind intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. The stabilized dose was not to exceed 10,000 lipase units/kg/day.
OG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule and was given orally daily in the first and second intervention periods; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0013 affected32 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0004 affected34 at risk EG0016 affected32 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0013 affected32 at risk
Abnormal faeces	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0013 affected32 at risk
Flatulence	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0013 affected32 at risk
Frequent bowel movements	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0012 affected32 at risk
Nausea	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0011 affected32 at risk
Steatorrhoea	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0014 affected32 at risk
Vomiting	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Early satiety	General disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0010 affected32 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0010 affected32 at risk
Injury	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Weight decreased	Investigations	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0012 affected32 at risk
Headache	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0005 affected34 at risk EG0010 affected32 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0002 affected34 at risk EG0010 affected32 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Abdominal tenderness	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Bowel sounds abnormal	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Constipation	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Infrequent bowel movements	Gastrointestinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Chest pain	General disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Oedema mucosal	General disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Pyrexia	General disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Otitis externa	Infections and infestations	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Anal injury	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Clubbing	Musculoskeletal and connective tissue disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Dizziness	Nervous system disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Vaginal burning sensation	Reproductive system and breast disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0000 affected34 at risk EG0011 affected32 at risk
Crackles lung	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0011 affected32 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk
Haematoma	Vascular disorders	MedDRA (8.1)	Non-systematic Assessment	These data represent AEs collected during both double blind treatment periods.	EG0001 affected34 at risk EG0010 affected32 at risk

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	EUR-1008 (APT-1008)	EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule was given orally daily in the first and second double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment. Participants received EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule was given orally daily at a fixed stabilized dose for 5 to 14 days during open-label dose normalization period 1 and for 7 days during open-label dose normalization period 2 which was maintained after each double-blind intervention period. The stabilized dose was not to exceed 10,000 lipase units per kilogram body weight per day (units/kg/day).			2	34	19	34
EG001	Placebo	Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule was given orally daily in the first and second double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for each double-blind intervention period was 2 days home treatment and 3 to 5 days hospital treatment.			0	32	16	32

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	SAEs for EUR-1008 occurred during the first open-label dose stabilization period, during which all participants were on EUR-1008.	EG0001 affected34 at risk EG0010 affected32 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (8.1)	Non-systematic Assessment	SAEs for EUR-1008 occurred during the first open-label dose stabilization period, during which all participants were on EUR-1008.	EG0001 affected34 at risk EG0010 affected32 at risk

ID	Term
D003550	Cystic Fibrosis
D010188	Exocrine Pancreatic Insufficiency