A Double-blind, Randomized, Multicenter, Cross-over Study to Compare the Effect of Creon N and Creon® on Fat Digestion in Subjects ≥ 12 Years of Age With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02137382
• Collaborator: (none)
• Enrollment: 41
• Locations: 7
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

maldigestion of dietary macronutrients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis	Drug: Creon®; Drug: Creon N	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Multicenter, Cross-over Study to Compare the Effect of Creon N and Creon® on Fat Digestion in Subjects ≥ 12 Years of Age With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Creon N, then Creon® Subjects first received Creon N for 5 days. After a washout period of 3 to 14 days, they received Creon® for 5 days. The Investigator calculated the total number of capsules per day needed to treat the subject with 8000 to <10000 lipase units per kg body weight and day, Capsules of both Creon N and Creon® contain 25000 lipase units.	Drug: Creon®; active comparator
Experimental: Creon® , then Creon N Subjects first received Creon® for 5 days. After a washout period of 3 to 14 days, they received Creon N for 5 days. The Investigator calculated the total number of capsules per day needed to treat the subject with 8000 to <10000 lipase units per kg body weight and day, Capsules of both Creon N and Creon® contain 25000 lipase units.	Drug: Creon N; experimental drug

Outcome Measures

Primary Outcome Measures

1. Coefficient of Fat Absorption (CFA) [5 days]

   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). [5 days]

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

2. Total Fat Excretion [5 days]

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

3. Stool Frequency [5 days]

   Stool frequency is the average of the daily number of stools recorded during the treatment period

4. Percentage of Days With no Flatulence [5 days]

   The percentage of days with no flatulence is calculated from the diary during the treatment period: 100*(number of days with no flatulence/number of days recorded in diary).

5. Percentage of Days With no Abdominal Pain [5 days]

   The percentage of days with no abdominal pain is calculated from the diary during the treatment period: 100*(number of days with no abdominal pain/ number of days recorded in diary).

6. Percentage of Days With Formed/Normal Stools [5 days]

   The percentage of days with formed/normal stools is calculated from the diary during the treatment period: 100*(number of days with formed/normal stools/ number of days recorded in diary).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Signed informed consent given by the subject, or the parents, or a legally acceptable representative. If required by the Institutional Review Board/Ethics Committee (IRB/IEC), assent will be given by the subject

• Age ≥ 12 years

• Subjects who are able to swallow capsules with each meal and snacks

• Diagnosis of Cystic Fibrosis (CF) confirmed by two positive chloride sweat tests or gene analysis

• Diagnosis of pancreatic exocrine insufficiency proven by:

1. Coefficient of fat absorption (CFA) < 70% without supplementation

2. or Human fecal elastase < 50 μg/g stool

• Currently receiving treatment with a commercially available pancreatic enzyme product and on a continuous dose of this product for more than 3 months

• Clinically stable condition without evidence of acute respiratory disease within 1 month of enrollment

• Stable body weight defined as no more than a 5% decline within 3 months of enrolment

• Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 30 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 (Depo-Provera™), an intrauterine device, or an oral contraceptive taken within the past 3 months where 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:

• Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, head, ears, eyes, nose, throat, dermatologic/connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except diabetes mellitus), neurologic/psychiatric, allergy, recent major surgery, or other relevant diseases as revealed by history, physical examination and/or laboratory assessments, which could limit participation in or completion of the study

• History of acute abdomen

• History of fibrosing colonopathy

• History of distal intestinal obstruction syndrome (DIOS) within 6 months prior to enrollment

• Solid organ transplant or surgery affecting the large bowel other than appendectomy

• Small bowel surgery that significantly affected absorptive capacity (e.g. gastrectomy or pancreatectomy)

• Pregnancy or lactation

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

• Celiac disease or Crohn's disease

• Known allergy to pancreatin or inactive ingredients (excipients) of pancreatin capsules

• Suspected non-compliance or non-cooperation

• Intake of experimental drugs within 30 days prior to study start

• Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subject's participation in or ability to complete the study

• Diagnosis of human immunodeficiency virus in medical history.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research facility ID ORG-000826	Budapest		Hungary	1122
2	Research facility ID ORG-000816	Debrecen		Hungary	4031
3	Research facility ID ORG-000827	Kaposvár		Hungary	7400
4	Research facility ID ORG-000825	Törökbálint		Hungary	2045
5	Research facility ID ORG-000829	Barcelona		Spain	8035
6	Research facility ID ORG-000828	Sevilla		Spain	41013
7	Research facility ID ORG-000815	Valencia		Spain	46026

Sponsors and Collaborators

• Abbott

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: NCT02137382
• Other Study ID Numbers: PANC3004; 2013-002819-10
• First Posted: May 13, 2014
• Last Update Posted: Jan 22, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Abbott: maldigestion of dietary macronutrients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis
• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis; Pancrelipase; Pancreatin

Study Results

Participant Flow

Recruitment Details	50 patients consented, between January and March 2014.
Pre-assignment Detail	41 of the 50 patients who consented were randomized; the 9 patients who were not randomized were screening failures.

Arm/Group Title	Sequence: Creon N/Creon®	Sequence: Creon®/Creon N
Arm/Group Description	Subjects first received Creon N for 5 days. After a washout period of 3 to 14 days, they received Creon® for 5 days. The Investigator calculated the total number of capsules per day needed to treat the subject with 8000 to <10000 lipase units per kg body weight and day, Capsules of both Creon N and Creon® contain 25000 lipase units.	Subjects first received Creon® for 5 days. After a washout period of 3 to 14 days, they received Creon N for 5 days. The Investigator calculated the total number of capsules per day needed to treat the subject with 8000 to <10000 lipase units per kg body weight and day, Capsules of both Creon N and Creon® contain 25000 lipase units.
Period Title: Cross-over Period 1
STARTED	20	21
COMPLETED	18	21
NOT COMPLETED	2	0
Period Title: Cross-over Period 1
STARTED	18	21
COMPLETED	18	21
NOT COMPLETED	0	0
Period Title: Cross-over Period 1
STARTED	18	21
COMPLETED	18	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequence Creon N/Creon® or Creon®/Creon N
Arm/Group Description	Participants who were randomized to receive either Creon N or Creon.
Overall Participants	41
Age (Count of Participants)
<=18 years	13 31.7%
Between 18 and 65 years	28 68.3%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.5 (8.0)
Sex: Female, Male (Count of Participants)
Female	22 53.7%
Male	19 46.3%
Region of Enrollment (Number) [Number]
Hungary	15 36.6%
Spain	26 63.4%

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	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon®: active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [percentage of fat intake]	88.1 (9.23)	89.5 (6.79)

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	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon®: active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [percentage of nitrogen intake]	87.7 (5.47)	87.8 (4.68)

3. Secondary Outcome

Title	Total Fat Excretion
Description	Total amount of fat excreted during the stool collection period in grams.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon® : active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [Grams]	48.1 (43.28)	42.3 (27.05)

4. Secondary Outcome

Title	Stool Frequency
Description	Stool frequency is the average of the daily number of stools recorded during the treatment period
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon®: active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [number of stools per day]	1.57 (0.6)	1.49 (0.6)

5. Secondary Outcome

Title	Percentage of Days With no Flatulence
Description	The percentage of days with no flatulence is calculated from the diary during the treatment period: 100*(number of days with no flatulence/number of days recorded in diary).
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon®: active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [percentage of days]	51.6 (46.65)	57.5 (43.31)

6. Secondary Outcome

Title	Percentage of Days With no Abdominal Pain
Description	The percentage of days with no abdominal pain is calculated from the diary during the treatment period: 100*(number of days with no abdominal pain/ number of days recorded in diary).
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon®: active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [percentage of days]	86.8 (22.91)	89.3 (19.67)

7. Secondary Outcome

Title	Percentage of Days With Formed/Normal Stools
Description	The percentage of days with formed/normal stools is calculated from the diary during the treatment period: 100*(number of days with formed/normal stools/ number of days recorded in diary).
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Creon®	Creon N
Arm/Group Description	Creon®: active comparator	Creon N: experimental drug
Measure Participants	38	38
Mean (Standard Deviation) [percentage of days]	79.8 (21.21)	73.6 (29.50)

Adverse Events

Arm/Group Title	Creon®		Creon N
Arm/Group Description	Creon®: active comparator		Creon N: experimental drug
All Cause Mortality
	Creon®		Creon N
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Creon®		Creon N
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Creon®		Creon N
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/39 (23.1%)		6/41 (14.6%)
Gastrointestinal disorders
Flatulence	3/39 (7.7%)	3	0/41 (0%)	0
Abdominal pain	1/39 (2.6%)	1	1/41 (2.4%)	1
Abdominal pain	1/39 (2.6%)	1	0/41 (0%)	0
Abdominal pain lower	0/39 (0%)	0	1/41 (2.4%)	1
Constipation	1/39 (2.6%)	1	1/41 (2.4%)	1
Diarrhea	0/39 (0%)	0	1/41 (2.4%)	1
Gastro intestinal hyper motility	1/39 (2.6%)	1	0/41 (0%)	0
Steatorrhea	1/39 (2.6%)	1	0/41 (0%)	0
Infections and infestations
viral rhinitis	1/39 (2.6%)	1	0/41 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	1/39 (2.6%)	1	0/41 (0%)	0
Investigations
Gastric pH decreased	0/39 (0%)	0	1/41 (2.4%)	1
Metabolism and nutrition disorders
decreased appetite	0/39 (0%)	0	1/41 (2.4%)	1
hypoglycaemia	0/39 (0%)	0	1/41 (2.4%)	1
Nervous system disorders
Headache	2/39 (5.1%)	2	0/41 (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.