Efficacy and Safety Study of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02415959
• Collaborator: AbbVie (Industry), LKF Laboratorium für Klinische Forschung GmbH (Other), Analytical Biochemical Laboratory (Other), Parexel (Industry), Datamap (Industry), Linical Co., Ltd. (Industry)
• Enrollment: 70
• Locations: 17
• Arms: 5
• Duration (Months): 4
• Patients Per Site: 4.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The objective of this study is to assess the efficacy and safety of different doses of Creon Immediate Release (IR) in comparison to Creon® 25,000 Delayed Release/Gastro-Resistant (DR/GR) in subjects with Pancreatic Exocrine Insufficiency (PEI) due to Cystis Fibrosis (CF).

Condition or Disease	Intervention/Treatment	Phase
Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis	Drug: Creon IR; Drug: Creon® (DR/GR)	Phase 2

Detailed Description

This study is a Phase II, randomized, parallel-group, active-controlled, double-blind, dose ranging, multicenter study with 4 different doses of Creon IR and one dose of the active control Creon® (DR/GR), administered in subjects of 12 years or older with PEI due to CF.

The study is divided into two periods: a screening period of 14 days and a double-blind treatment period of 6 to 7 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Official Title: A Phase II, Multicenter, Parallel-Group, Active-Controlled, Randomized, Double-blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Different Doses of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Creon IR low dose Creon IR 300 Ph. Eur. U lipase/g fat/day, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)	Drug: Creon IR
Experimental: Creon IR medium dose Creon IR 1,200 Ph. Eur. U lipase/g fat/day, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)	Drug: Creon IR
Experimental: Creon IR high dose Creon IR 2,400 Ph. Eur. U lipase/g fat/day, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)	Drug: Creon IR
Experimental: Creon IR maximum dose Creon IR 4,000 Ph. Eur. U lipase/g fat/day, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)	Drug: Creon IR
Active Comparator: Creon® (DR/GR) Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat/day, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)	Drug: Creon® (DR/GR)

Outcome Measures

Primary Outcome Measures

1. Coefficient of Fat Absorption (CFA) [End of the 6 to 7 days double-blind treatment period]

   CFA is calculated from fat intake and fat excretion, according to the formula: CFA (%) = 100 [fat intake - fat excretion] / fat intake

Secondary Outcome Measures

1. Coefficient of Nitrogen Absorption (CNA) [End of the 6 to 7 days double-blind treatment period]

   CNA is calculated from nitrogen intake and nitrogen excretion, according to the formula: CNA (%) = 100 [nitrogen intake - nitrogen excretion] / nitrogen intake)

2. Stool Fat Content [End of the 6 to 7 days double-blind treatment period]

   Total amount of fat excreted during the stool collection period in grams.

3. Stool Weight [End of the 6 to 7 days double-blind treatment period]

   Total amount of stool weight during the collection period in grams

Other Outcome Measures

1. Treatment Emergent Adverse Events [From randomization to end of Double Blind period plus 1 day, i.e. up to 7/8 days]

   Treatment emergent adverse events will be summarized per treatment group

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has voluntarily signed and dated the Informed Consent Form (ICF). For subjects aged less than 18 years, the parents, or a legally acceptable representative, must sign consent and, as required by the Independent Ethics Committee (IEC), assent will be given by the subject.

2. Subject is 12 years old or older at the time of consent signature.

3. Subject has a diagnosis of CF previously confirmed by:

• a sweat chloride test > or equal to 60 mmol/Ls and/or

• two CF causing Cystic Fibrosis trans membrane conductance regulator (CFTR) mutations and

• CF clinical features

1. Subject has a documented clinically confirmed diagnosis of pancreatic exocrine insufficiency.

2. Subject has human fecal elastase < 100 µg/g stool at screening

3. Subject has PEI that is currently clinically controlled (no clinically overt steatorrhea or diarrhea) under treatment with a commercially available Pancreatic enzyme Replacement Therapy (PERT), on an individually established dose regimen for more than 3 months, with a daily dose not exceeding 10,000 U lipase/kg/day.

4. Females of child-bearing potential and sexually active with men should agree to continue using a medically acceptable method of birth control throughout the study and for 7 days immediately after the last dose of study drug. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (e.g., Depo Provera™), an intrauterine device, or an oral contraceptive taken continually within the past three months and which the subject agrees to continue using during the study or to adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide.

Exclusion Criteria:

1. Subject is < 18 years of age and has a Body Mass Index (BMI) Z-Score below -1.5 (minus 1.5)

2. Subject has a history of any of the following gastrointestinal disorders:

• pancreatitis within 6 months prior to study entry;

• fibrosing colonopathy;

• distal ileal obstruction syndrome (DIOS) within 6 months prior to study entry;

• celiac disease;

• gastric bypass or partial/total gastrectomy;

• Crohn's disease;

• small bowel surgery (other than minor resection due to meconium ileus without resulting in malabsorption syndrome).

• Any type of malignancy involving the digestive tract in the last 5 years.

1. Subjects with diabetes mellitus, for which the study specific dietary requirements may not be appropriate.

2. Subject has a history of other endocrine or respiratory (except mild asthma) medical illness non-related to CF, which might limit participation in or completion of the study.

3. Subject has a history of any clinically significant neurological, cardiac, renal, hepatic (including Hepatitis B or C), hematologic or psychiatric disease or disorder, or any other uncontrolled medical illness (except cystic fibrosis) which might limit participation in or completion of the study.

4. Subjects requiring concomitant treatment with any medication not allowed by the protocol or is expected to be needed.

5. Subjects requiring Naso-gastric, G-tubes or J-tubes.

6. Subject is currently participating in any other interventional clinical study or has taken any experimental drug within 30 days prior to Screening.

7. Subject is known to be HIV-positive.

8. Subject has a history of allergic reaction or significant sensitivity to pancreatin or inactive ingredients (excipients) of Creon® (DR/GR) or Creon IR

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dětská nemocnice FN Brno, Centrum pro cystickou fibrozu	Brno		Czech Republic	61300
2	Klinika nemocí plicních a TBC	Brno		Czech Republic	62500
3	Magyar Imre Kórház	Ajka		Hungary	8400
4	Kenézy Gyula Kórház	Debrecen		Hungary	4031
5	Kaposi Mór Oktató Kórház	Kaposvár		Hungary	7400
6	Tüdőgyógyintézet Törökbálint	Törökbálint		Hungary	2045
7	Centrum Medyczne Karpacz S.A.	Karpacz		Poland	58-540
8	Wojewódzki Szpital Specjalistyczny Im M Kopernika W Łodzi	Lodzi		Poland	93-513
9	Janusz Stankiewicz Sanatorium ""Cassia-Villa Medica	Rabka		Poland	34-700
10	Podkarpacki Ośrodek Pulmonologii i Alergologii	Rzeszów		Poland	35-612
11	ENEL-MED Szpital Centrum	Warszawa		Poland	01-195
12	Hospital Vall d ´Hebron	Barcelona		Spain	08035
13	Hospital Universitario de La Princesa	Madrid		Spain	28006
14	Hospital Universitario La Paz	Madrid		Spain	28046
15	Hospital Carlos Haya, Hospital Civil, Secretaria de Endocrinologia	Málaga		Spain	29009
16	Hospital Universitario Virgen del Rocío, Hospital de la Mujer	Sevilla		Spain	41013
17	Hospital La Fé Valencia	Valencia		Spain	46026

Sponsors and Collaborators

• Abbott
• AbbVie
• LKF Laboratorium für Klinische Forschung GmbH
• Analytical Biochemical Laboratory
• Parexel
• Datamap
• Linical Co., Ltd.

Investigators

• Study Director: Suntje Sander-Struckmeier, PhD, Abbott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT02415959
• Other Study ID Numbers: PANC2002; 2014-004519-35
• First Posted: Apr 14, 2015
• Last Update Posted: Apr 4, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Abbott: Exocrine Pancreatic Insufficiency
• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis; Pancrelipase; Pancreatin

Study Results

Participant Flow

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
Period Title: Overall Study
STARTED	14	14	14	14	14
COMPLETED	14	13	14	13	14
NOT COMPLETED	0	1	0	1	0

Baseline Characteristics

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)	Total
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)	Total of all reporting groups
Overall Participants	14	14	14	14	14	70
Age (Count of Participants)
<=18 years	4 28.6%	5 35.7%	5 35.7%	8 57.1%	4 28.6%	26 37.1%
Between 18 and 65 years	10 71.4%	9 64.3%	9 64.3%	6 42.9%	10 71.4%	44 62.9%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.7 (7.6)	22.9 (8.5)	22.0 (7.3)	19.7 (8.4)	22.6 (7.1)	22.4 (7.7)
Sex: Female, Male (Count of Participants)
Female	6 42.9%	9 64.3%	7 50%	5 35.7%	6 42.9%	33 47.1%
Male	8 57.1%	5 35.7%	7 50%	9 64.3%	8 57.1%	37 52.9%
Region of Enrollment (participants) [Number]
Hungary	3 21.4%	3 21.4%	3 21.4%	3 21.4%	3 21.4%	15 21.4%
Czech Republic	1 7.1%	1 7.1%	1 7.1%	1 7.1%	1 7.1%	5 7.1%
Poland	6 42.9%	6 42.9%	6 42.9%	6 42.9%	6 42.9%	30 42.9%
Spain	4 28.6%	4 28.6%	4 28.6%	4 28.6%	4 28.6%	20 28.6%

Outcome Measures

1. Primary Outcome

Title	Coefficient of Fat Absorption (CFA)
Description	CFA is calculated from fat intake and fat excretion, according to the formula: CFA (%) = 100 [fat intake - fat excretion] / fat intake
Time Frame	End of the 6 to 7 days double-blind treatment period

Outcome Measure Data

Analysis Population Description

Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
Measure Participants	13	13	14	13	13
Mean (Standard Deviation) [percentage of fat intake]	71.0 (12.4)	70.9 (13.9)	71.8 (15.2)	75.9 (9.2)	92.3 (3.7)

2. Secondary Outcome

Title	Coefficient of Nitrogen Absorption (CNA)
Description	CNA is calculated from nitrogen intake and nitrogen excretion, according to the formula: CNA (%) = 100 [nitrogen intake - nitrogen excretion] / nitrogen intake)
Time Frame	End of the 6 to 7 days double-blind treatment period

Outcome Measure Data

Analysis Population Description

Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
Measure Participants	13	13	14	13	13
Mean (Standard Deviation) [percentage of nitrogen intake]	71.0 (10.0)	73.2 (6.4)	76.2 (8.1)	79.9 (7.3)	84.8 (4.3)

3. Secondary Outcome

Title	Stool Fat Content
Description	Total amount of fat excreted during the stool collection period in grams.
Time Frame	End of the 6 to 7 days double-blind treatment period

Outcome Measure Data

Analysis Population Description

Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
Measure Participants	13	13	14	13	13
Mean (Standard Deviation) [gram per 72 hours]	87.5 (37.5)	87.1 (41.0)	84.1 (44.9)	73.0 (28.2)	23.5 (11.3)

4. Secondary Outcome

Title	Stool Weight
Description	Total amount of stool weight during the collection period in grams
Time Frame	End of the 6 to 7 days double-blind treatment period

Outcome Measure Data

Analysis Population Description

Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
Measure Participants	13	13	14	13	13
Mean (Standard Deviation) [gram per 72 hours]	889.0 (294.2)	905.3 (225.7)	793.8 (279.8)	755.7 (383.2)	545.7 (256.3)

5. Other Pre-specified Outcome

Title	Treatment Emergent Adverse Events
Description	Treatment emergent adverse events will be summarized per treatment group
Time Frame	From randomization to end of Double Blind period plus 1 day, i.e. up to 7/8 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Creon IR Low Dose	Creon IR Medium Dose	Creon IR High Dose	Creon IR Maximum Dose	Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR	Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR	Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR	Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR	Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
Measure Participants	14	14	14	14	14
Number [participants]	10 71.4%	9 64.3%	7 50%	9 64.3%	7 50%

Adverse Events

Arm/Group Title	Creon IR Low Dose		Creon IR Medium Dose		Creon IR High Dose		Creon IR Maximum Dose		Creon® (DR/GR)
Arm/Group Description	Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units) Creon IR		Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units) Creon IR		Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units) Creon IR		Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon IR		Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units) Creon® (DR/GR)
All Cause Mortality
	Creon IR Low Dose		Creon IR Medium Dose		Creon IR High Dose		Creon IR Maximum Dose		Creon® (DR/GR)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Creon IR Low Dose		Creon IR Medium Dose		Creon IR High Dose		Creon IR Maximum Dose		Creon® (DR/GR)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		1/14 (7.1%)		0/14 (0%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
infective pulmonary exacerbation due to CF	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Creon IR Low Dose		Creon IR Medium Dose		Creon IR High Dose		Creon IR Maximum Dose		Creon® (DR/GR)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/14 (71.4%)		9/14 (64.3%)		7/14 (50%)		9/14 (64.3%)		7/14 (50%)
Gastrointestinal disorders
Abdominal pain	6/14 (42.9%)	6	8/14 (57.1%)	8	6/14 (42.9%)	6	4/14 (28.6%)	4	2/14 (14.3%)	2
Flatulence	2/14 (14.3%)	2	2/14 (14.3%)	2	6/14 (42.9%)	6	3/14 (21.4%)	3	2/14 (14.3%)	2
Abdominal distension	3/14 (21.4%)	3	3/14 (21.4%)	3	0/14 (0%)	0	2/14 (14.3%)	2	1/14 (7.1%)	1
Diarrhea	4/14 (28.6%)	4	4/14 (28.6%)	4	2/14 (14.3%)	2	1/14 (7.1%)	1	1/14 (7.1%)	1
faeces soft	2/14 (14.3%)	2	1/14 (7.1%)	1	1/14 (7.1%)	1	1/14 (7.1%)	1	2/14 (14.3%)	2
Nervous system disorders
Headache	1/14 (7.1%)	1	0/14 (0%)	0	1/14 (7.1%)	1	1/14 (7.1%)	1	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.