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

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2014-004519-35-HU
• Date of registration: 12/11/2014
• Prospective Registration: Yes
• Primary sponsor: Abbott Laboratories GmbH
• Public 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
• Scientific 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
• Date of first enrolment: 09/01/2015
• Target sample size: 78
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004519-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Czech Republic, Hungary, Spain, United Kingdom

Contacts

• Name: Hanneke Van Assche
• Affiliation: Abbott Healthcare Products BV

• Name: Hanneke Van Assche
• Affiliation: Abbott Healthcare Products BV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject has voluntarily signed and dated the ICF. For subjects aged less than 18 years, the parents, or a legally acceptable representative, must sign consent and, as required by the 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 CFTR mutations and
- CF clinical features7,8.
4. Subject has a documented clinically confirmed diagnosis of pancreatic exocrine insufficiency.
5. Subject has human fecal elastase < 100 µg/g stool at screening.
6. Subject has PEI that is currently clinically controlled (no clinically overt steatorrhea or diarrhea) under treatment with a commercially available PERT, on an individually established dose regimen for more than 3 months, with a daily dose not exceeding 10,000 U lipase/kg/day.
7. Females of child-bearing potential 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 39
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 39
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Subject is < 18 years of age and has a Body Mass Index (BMI) Z-Score below -1.59 (minus 1.5).
2. Subject has a history of any of the following gastrointestinal disorders:
a. pancreatitis within 6 months prior to study entry;
b. fibrosing colonopathy;
c. distal ileal obstruction syndrome (DIOS) within 6 months prior to study entry;
d. celiac disease;
e. gastric bypass or partial/total gastrectomy;
f. Crohn’s disease;
g. small bowel surgery (other than minor resection due to meconium ileus without resulting in malabsorption syndrome).
h. Any type of malignancy involving the digestive tract in the last 5 years
3. Subjects with diabetes mellitus, for which the study specific dietary requirements may not be appropriate (See Section 8.1.1).
4. 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.
5. 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.
6. Subjects requiring concomitant treatment with any medication not allowed by the protocol or is expected to be needed.
7. Subjects requiring Naso-gastric, G-tubes or J-tubes.
8. Subject is currently participating in any other interventional clinical study or has taken any experimental drug within 30 days prior to Screening.
9. Subject is known to be HIV-positive.
10. Subject has a history of allergic reaction or significant sensitivity to pancreatin or inactive ingredients (excipients) of Creon® (DR/GR) or Creon IR



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pancreatic exocrine Insufficiency due to Cystic Fibrosis

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: CREON IR
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NOT APPLICABLE
CAS Number: 8049-47-6
Current Sponsor code: CREON IR
Other descriptive name: PANCREATIN (Pancreas Powder)
Concentration unit: U unit(s)
Concentration type: range
Concentration number: 4000-30000
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Kreon 25 000
Product Name: Creon® 25,000
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not assigned
CAS Number: 8049-47-6
Other descriptive name: PANCREATIN (Pancreas Powder)
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 25000-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy criterion is the CFA (Coefficient of Fat Absorption).
CFA will be calculated from fat intake and fat excretion, according to the formula:
CFA (%) = 100 [fat intake – fat excretion] / fat intake

Timepoint(s) of evaluation of this end point: The values at the end of the double-blind treatment period of the four different doses of Creon IR, and of the active control Creon® will be compared .

Main Objective: To compare and model the efficacy of four different doses of Creon Immediate Release (IR) and the active control (Creon® (Delayed Release/Gastro-Resistant) [Creon® DR/GR]) in subjects with pancreatic exocrine insufficiency (PEI) due to cystic fibrosis (CF). The primary efficacy objective is based on the evaluation of fat digestion as measured by coefficient of fat absorption (CFA) (%).

Secondary Objective: The secondary efficacy objective is to compare protein digestion (measured by coefficient of nitrogen absorption [CNA]), stool fat content and stool weight, of four different doses of Creon IR and Creon® (DR/GR) in subjects with PEI due to CF.

The safety objective is to determine the clinical safety of Creon IR based on the evaluation of clinical symptomatology associated with PEI (stool frequency, stool consistency, abdominal pain, flatulence), vital signs, physical examination findings, safety laboratory values and adverse events (AEs) in subjects with PEI due to CF.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The values at the end of the double-blind treatment period of the four different doses of Creon IR, and of the active control Creon®, will be compared .

Safety parameters are assessed throughout the study.

Secondary end point(s): Secondary efficacy criteria are the CNA (Coefficient of Nitrogen Absorption), stool fat content, and stool weight.
CNA will be calculated from nitrogen intake and nitrogen according to the formula:
CNA (%) = 100 [nitrogen intake – nitrogen excretion] / nitrogen intake.

The safety data collected during the study are vital signs, physical
examination, safety laboratory values and adverses events.

Secondary ID(s)

PANC2002

Source(s) of Monetary Support

Abbott Laboratories GmbH