PR-018: An Open-Label, Safety Extension of Study PR-011

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01131507
• Collaborator: (none)
• Enrollment: 15
• Locations: 6
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study to evaluate long term safety and effect on ability to thrive of EUR-1008 (APT-1008) 3,000 lipase units (Zenpep® [pancrelipase] delayed release capsules) in infants with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF).

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Exocrine Pancreatic Insufficiency	Drug: EUR-1008 (APT-1008)	Phase 4

Detailed Description

This is a multi-center, open-label, safety extension of Aptalis (formerly Eurand) study PR-011 (NCT01100606) in pediatric participants with EPI due to CF. The study will be carried out in participants who completed the PR-011 study.

The study is comprised of 5 visits: an enrollment visit, treatment visit 1 (3 months), treatment visit 2 (6 months), treatment visit 3 (9 months) and treatment visit 4 (12 months). Once determined eligible for participation, participants will be enrolled into the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label, Safety Extension of Study PR-011 Titled: A Multicenter, Randomized, Open-Label, Crossover Study to Evaluate the Mode of Administration and Safety of EUR-1008 in Infants 1 to 12 Months of Age With Exocrine Pancreatic Insufficiency (EPI) Associated With Cystic Fibrosis (CF)
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: EUR-1008 (APT-1008)

Drug: EUR-1008 (APT-1008); EUR-1008 (APT-1008) (Zenpep® [pancrelipase] 3,000 lipase units delayed release capsules) from open capsules mixed with a small amount of apple juice or apple sauce will be administered orally starting at the same dose as administered at the end of study PR-011 (NCT01100606), with dose increments of 3,000 lipase units. The dose will be adjusted based on participants' age and body weight. Total dose will not exceed 10,000 lipase units per kilogram (kg) of body weight per day unless clinically indicated. Total duration of study treatment will be up to 12 months.; Other Names: Zenpep® (pancrelipase) 3,000 lipase units delayed release capsules

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to Month 12 or early termination]

   TEAE was any event not present prior to exposure to study drug or any event already present that worsened in either intensity or frequency following exposure to test drug. Serious AE (SAE) was any event that resulted in death, immediately life threatening, hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Number of participants with TEAEs, SAEs, TEAE's relationship to study drug (unrelated, possible and probable) and on the basis of severity (mild [minimal/no treatment and did not interfere with daily activities], moderate [resulted in a low level of inconvenience or concern with the therapeutic measures and may have caused some interference with functioning] and severe [interrupted participant's usual daily activity, may have required systemic drug therapy or other treatment and were usually incapacitating]) with a frequency threshold of above 5% were reported.

Secondary Outcome Measures

1. Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 [Baseline, Month 3, 6, 9 and 12]

   Participant's ability to thrive was evaluated through growth percentiles for weight-for-age, length-for-age and weight-for-length recorded on Center for Disease Control and Prevention (CDC) growth charts during each treatment visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 12 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant's parent or guardian signed informed consent form (ICF)

• Participants who have completed study PR-011 (NCT01100606)

Exclusion Criteria:

• Participant having any condition that would, in the investigator's opinion, limit the participant's ability to complete the study or will result in excess risk to the participant that is above the standard of care

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nemours Children's Clinic	Jacksonville	Florida	United States	32250
2	Children's Lung Specialists Ltd.	Las Vegas	Nevada	United States	89107
3	Akron Children's Hospital	Akron	Ohio	United States	44308
4	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
5	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
6	Cystic Fibrosis Care Center	Houston	Texas	United States	77030

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: NCT01131507
• Other Study ID Numbers: PR-018
• First Posted: May 27, 2010
• Last Update Posted: Mar 21, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Forest Laboratories: Exocrine Pancreatic Insufficiency; Infants with CF
• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis; Pancrelipase

Study Results

Participant Flow

Recruitment Details	Participants who completed previous study PR-011 (NCT01100606) and consented to continue treatment with EUR-1008 (APT-1008) 3,000 lipase units were enrolled in this study.

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] 3,000 lipase units delayed release capsules) from open capsules mixed with a small amount of apple juice or apple sauce orally starting at the same dose as administered at the end of study PR-011 (NCT01100606), with dose increments of 3,000 lipase units. The dose was adjusted based on participants' age and body weight. Total dose not to exceed 10,000 lipase units per kilogram (kg) of body weight per day unless clinically indicated. Total duration of study treatment was up to 12 months.
Period Title: Overall Study
STARTED	15
COMPLETED	12
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] 3,000 lipase units delayed release capsules) from open capsules mixed with a small amount of apple juice or apple sauce orally starting at the same dose as administered at the end of study PR-011 (NCT01100606), with dose increments of 3,000 lipase units. The dose was adjusted based on participants' age and body weight. Total dose not to exceed 10,000 lipase units per kg body weight per day unless clinically indicated. Total duration of study treatment was up to 12 months.
Overall Participants	15
Age (months) [Median (Full Range) ]
Median (Full Range) [months]	9.0 (3.27)
Sex: Female, Male (Count of Participants)
Female	6 40%
Male	9 60%
Weight (kilogram) [Median (Full Range) ]
Median (Full Range) [kilogram]	7.80 (1.296)
Length (centimeter) [Median (Full Range) ]
Median (Full Range) [centimeter]	68.5 (5.98)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	TEAE was any event not present prior to exposure to study drug or any event already present that worsened in either intensity or frequency following exposure to test drug. Serious AE (SAE) was any event that resulted in death, immediately life threatening, hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Number of participants with TEAEs, SAEs, TEAE's relationship to study drug (unrelated, possible and probable) and on the basis of severity (mild [minimal/no treatment and did not interfere with daily activities], moderate [resulted in a low level of inconvenience or concern with the therapeutic measures and may have caused some interference with functioning] and severe [interrupted participant's usual daily activity, may have required systemic drug therapy or other treatment and were usually incapacitating]) with a frequency threshold of above 5% were reported.
Time Frame	Up to Month 12 or early termination

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug.

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] 3,000 lipase units delayed release capsules) from open capsules mixed with a small amount of apple juice or apple sauce orally starting at the same dose as administered at the end of study PR-011 (NCT01100606), with dose increments of 3,000 lipase units. The dose was adjusted based on participants' age and body weight. Total dose not to exceed 10,000 lipase units per kg body weight per day unless clinically indicated. Total duration of study treatment was up to 12 months.
Measure Participants	15
All TEAEs	15 100%
SAEs	3 20%
Unrelated TEAEs	10 66.7%
Possibly related TEAEs	4 26.7%
Probably related TEAEs	1 6.7%
Mild TEAEs	5 33.3%
Moderate TEAEs	8 53.3%
Severe TEAEs	2 13.3%

2. Secondary Outcome

Title	Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12
Description	Participant's ability to thrive was evaluated through growth percentiles for weight-for-age, length-for-age and weight-for-length recorded on Center for Disease Control and Prevention (CDC) growth charts during each treatment visit.
Time Frame	Baseline, Month 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Here, 'n' specifies number of participants who were evaluable for various categories at each time point.

Arm/Group Title	EUR-1008 (APT-1008)
Arm/Group Description	EUR-1008 (APT-1008) (Zenpep® [pancrelipase] 3,000 lipase units delayed release capsules) from open capsules mixed with a small amount of apple juice or apple sauce orally starting at the same dose as administered at the end of study PR-011 (NCT01100606), with dose increments of 3,000 lipase units. The dose was adjusted based on participants' age and body weight. Total dose not to exceed 10,000 lipase units per kg body weight per day unless clinically indicated. Total duration of study treatment was up to 12 months.
Measure Participants	15
Weight-for-age: Baseline (n=15)	22.0
Weight-for-age: Change at Month 3 (n=15)	2.0
Weight-for-age: Change at Month 6 (n=13)	6.0
Weight-for-age: Change at Month 9 (n=12)	4.0
Weight-for-age: Change at Month 12 (n=12)	5.5
Length-for-age: Baseline (n=14)	36.5
Length-for-age: Change at Month 3 (n=14)	2.0
Length-for-age: Change at Month 6 (n=12)	2.0
Length-for-age: Change at Month 9 (n=12)	11.0
Length-for-age: Change at Month 12 (n=12)	0.5
Weight-for-length: Baseline (n=14)	41.5
Weight-for-length: Change at Month 3 (n=14)	0.5
Weight-for-length: Change at Month 6 (n=12)	13.5
Weight-for-length: Change at Month 9 (n=12)	9.0
Weight-for-length: Change at Month 12 (n=12)	10.5

Adverse Events

Time Frame	Up to Month 12 or early termination
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) (Zenpep® [pancrelipase] 3,000 lipase units delayed release capsules) from open capsules mixed with a small amount of apple juice or apple sauce will be administered orally starting at the same dose as administered at the end of study PR-011 (NCT01100606), with dose increments of 3,000 lipase units. The dose was adjusted based on participants' age and body weight. Total dose not to exceed 10,000 lipase units per kg body weight per day unless clinically indicated. Total duration of study treatment was up to 12 months.
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	3/15 (20%)
Immune system disorders
Anaphylactic shock	1/15 (6.7%)
Infections and infestations
Bronchopneumonia	1/15 (6.7%)
Viral infection	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	EUR-1008 (APT-1008)
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Cardiac disorders
Tachycardia	1/15 (6.7%)
Congenital, familial and genetic disorders
Cystic fibrosis lung	3/15 (20%)
Ear and labyrinth disorders
Cerumen impaction	1/15 (6.7%)
Eye disorders
Eyelid margin crusting	1/15 (6.7%)
Gastrointestinal disorders
Diarrhoea	5/15 (33.3%)
Vomiting	5/15 (33.3%)
Steatorrhoea	4/15 (26.7%)
Abnormal faeces	3/15 (20%)
Constipation	3/15 (20%)
Abdominal distension	2/15 (13.3%)
Faecal volume increased	2/15 (13.3%)
Flatulence	2/15 (13.3%)
Post-tussive vomiting	2/15 (13.3%)
Teething	2/15 (13.3%)
Faeces hard	1/15 (6.7%)
Frequent bowel movements	1/15 (6.7%)
Haematochezia	1/15 (6.7%)
Malabsorption	1/15 (6.7%)
Salivary hypersecretion	1/15 (6.7%)
General disorders
Pyrexia	10/15 (66.7%)
Fatigue	3/15 (20%)
Immune system disorders
Drug hypersensitivity	1/15 (6.7%)
Infections and infestations
Upper respiratory tract infection	6/15 (40%)
Otitis media	5/15 (33.3%)
Bronchitis	2/15 (13.3%)
Pseudomonas infection	2/15 (13.3%)
Rhinitis	2/15 (13.3%)
Sinusitis	2/15 (13.3%)
Acute sinusitis	1/15 (6.7%)
Croup infectious	1/15 (6.7%)
Ear infection	1/15 (6.7%)
Gastroenteritis	1/15 (6.7%)
Influenza	1/15 (6.7%)
Nasopharyngitis	1/15 (6.7%)
Oral candidiasis	1/15 (6.7%)
Pharyngitis streptococcal	1/15 (6.7%)
Pneumonia	1/15 (6.7%)
Respiratory tract infection	1/15 (6.7%)
Staphylococcal infection	1/15 (6.7%)
Investigations
Weight decreased	2/15 (13.3%)
Band neutrophil count increased	1/15 (6.7%)
Pseudomonas test positive	1/15 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	2/15 (13.3%)
Vitamin D deficiency	2/15 (13.3%)
Weight gain poor	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	12/15 (80%)
Cough	11/15 (73.3%)
Wheezing	8/15 (53.3%)
Nasal congestion	7/15 (46.7%)
Productive cough	4/15 (26.7%)
Respiratory tract congestion	2/15 (13.3%)
Rhonchi	2/15 (13.3%)
Asthma	1/15 (6.7%)
Dyspnoea	1/15 (6.7%)
Haemoptysis	1/15 (6.7%)
Oropharyngeal pain	1/15 (6.7%)
Rales	1/15 (6.7%)
Sputum increased	1/15 (6.7%)
Tonsillar hypertrophy	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Dermatitis diaper	2/15 (13.3%)
Rash	1/15 (6.7%)
Rash generalised	1/15 (6.7%)
Rash macular	1/15 (6.7%)
Seborrhoea	1/15 (6.7%)

Limitations/Caveats

[Not Specified]

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.