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

• ClinicalTrials.gov Identifier: NCT01131507
• Recruitment Status: Completed
• First Posted: May 27, 2010
• Results First Posted: March 7, 2014
• Last Update Posted: March 21, 2017
• Sponsor: Forest Laboratories
• Information provided by (Responsible Party): Forest Laboratories

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Cystic Fibrosis; Exocrine Pancreatic Insufficiency
• Intervention: Drug: EUR-1008 (APT-1008)
• Enrollment: 15

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.
Pre-assignment Details

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
Reason Not Completed
Adverse Event	1
Lost to Follow-up	1
Withdrawal by Subject	1

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 Number of Baseline Participants		15
Baseline Analysis Population Description		Safety population included all participants who received at least 1 dose of study drug.
Age, Continuous; Median (Full Range); Unit of measure: Months
	Number Analyzed	15 participants
		9.0; (3 to 14)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	Female	6 40.0%
	Male	9 60.0%
Weight; Median (Full Range); Unit of measure: Kilogram
	Number Analyzed	15 participants
		7.80; (6.0 to 10.6)
Length [1]; Median (Full Range); Unit of measure: Centimeter
	Number Analyzed	15 participants
		68.5; (59 to 79)
		[1] Measure Description: Number of participants evaluable for this baseline characteristic = 14

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.
Overall Number of Participants Analyzed	15
Measure Type: Number; Unit of Measure: participants
All TEAEs	15
SAEs	3
Unrelated TEAEs	10
Possibly related TEAEs	4
Probably related TEAEs	1
Mild TEAEs	5
Moderate TEAEs	8
Severe TEAEs	2

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.
Overall Number of Participants Analyzed	15
Median (Full Range); Unit of Measure: growth percentile
Weight-for-age: Baseline (n=15)	22.0; (2 to 91)
Weight-for-age: Change at Month 3 (n=15)	2.0; (-18 to 34)
Weight-for-age: Change at Month 6 (n=13)	6.0; (-35 to 34)
Weight-for-age: Change at Month 9 (n=12)	4.0; (-42 to 34)
Weight-for-age: Change at Month 12 (n=12)	5.5; (-45 to 36)
Length-for-age: Baseline (n=14)	36.5; (1 to 74)
Length-for-age: Change at Month 3 (n=14)	2.0; (-22 to 30)
Length-for-age: Change at Month 6 (n=12)	2.0; (-23 to 28)
Length-for-age: Change at Month 9 (n=12)	11.0; (-24 to 34)
Length-for-age: Change at Month 12 (n=12)	0.5; (-27 to 53)
Weight-for-length: Baseline (n=14)	41.5; (8 to 98)
Weight-for-length: Change at Month 3 (n=14)	0.5; (-12 to 41)
Weight-for-length: Change at Month 6 (n=12)	13.5; (-17 to 47)
Weight-for-length: Change at Month 9 (n=12)	9.0; (-54 to 31)
Weight-for-length: Change at Month 12 (n=12)	10.5; (-57 to 48)

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 (%)
Total	--/--
Serious Adverse Events
	EUR-1008 (APT-1008)
	Affected / at Risk (%)
Total	3/15 (20.00%)
Immune system disorders
Anaphylactic shock * 1 [1]	1/15 (6.67%)
Infections and infestations
Bronchopneumonia * 1	1/15 (6.67%)
Viral infection * 1	1/15 (6.67%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (13.0); [1] This AE was an acute reaction to peanuts and not related to study drug.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	EUR-1008 (APT-1008)
	Affected / at Risk (%)
Total	15/15 (100.00%)
Cardiac disorders
Tachycardia * 1	1/15 (6.67%)
Congenital, familial and genetic disorders
Cystic fibrosis lung * 1	3/15 (20.00%)
Ear and labyrinth disorders
Cerumen impaction * 1	1/15 (6.67%)
Eye disorders
Eyelid margin crusting * 1	1/15 (6.67%)
Gastrointestinal disorders
Diarrhoea * 1	5/15 (33.33%)
Vomiting * 1	5/15 (33.33%)
Steatorrhoea * 1	4/15 (26.67%)
Abnormal faeces * 1	3/15 (20.00%)
Constipation * 1	3/15 (20.00%)
Abdominal distension * 1	2/15 (13.33%)
Faecal volume increased * 1	2/15 (13.33%)
Flatulence * 1	2/15 (13.33%)
Post-tussive vomiting * 1	2/15 (13.33%)
Teething * 1	2/15 (13.33%)
Faeces hard * 1	1/15 (6.67%)
Frequent bowel movements * 1	1/15 (6.67%)
Haematochezia * 1	1/15 (6.67%)
Malabsorption * 1	1/15 (6.67%)
Salivary hypersecretion * 1	1/15 (6.67%)
General disorders
Pyrexia * 1	10/15 (66.67%)
Fatigue * 1	3/15 (20.00%)
Immune system disorders
Drug hypersensitivity * 1	1/15 (6.67%)
Infections and infestations
Upper respiratory tract infection * 1	6/15 (40.00%)
Otitis media * 1	5/15 (33.33%)
Bronchitis * 1	2/15 (13.33%)
Pseudomonas infection * 1	2/15 (13.33%)
Rhinitis * 1	2/15 (13.33%)
Sinusitis * 1	2/15 (13.33%)
Acute sinusitis * 1	1/15 (6.67%)
Croup infectious * 1	1/15 (6.67%)
Ear infection * 1	1/15 (6.67%)
Gastroenteritis * 1	1/15 (6.67%)
Influenza * 1	1/15 (6.67%)
Nasopharyngitis * 1	1/15 (6.67%)
Oral candidiasis * 1	1/15 (6.67%)
Pharyngitis streptococcal * 1	1/15 (6.67%)
Pneumonia * 1	1/15 (6.67%)
Respiratory tract infection * 1	1/15 (6.67%)
Staphylococcal infection * 1	1/15 (6.67%)
Investigations
Weight decreased * 1	2/15 (13.33%)
Band neutrophil count increased * 1	1/15 (6.67%)
Pseudomonas test positive * 1	1/15 (6.67%)
Metabolism and nutrition disorders
Decreased appetite * 1	2/15 (13.33%)
Vitamin D deficiency * 1	2/15 (13.33%)
Weight gain poor * 1	1/15 (6.67%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea * 1	12/15 (80.00%)
Cough * 1	11/15 (73.33%)
Wheezing * 1	8/15 (53.33%)
Nasal congestion * 1	7/15 (46.67%)
Productive cough * 1	4/15 (26.67%)
Respiratory tract congestion * 1	2/15 (13.33%)
Rhonchi * 1	2/15 (13.33%)
Asthma * 1	1/15 (6.67%)
Dyspnoea * 1	1/15 (6.67%)
Haemoptysis * 1	1/15 (6.67%)
Oropharyngeal pain * 1	1/15 (6.67%)
Rales * 1	1/15 (6.67%)
Sputum increased * 1	1/15 (6.67%)
Tonsillar hypertrophy * 1	1/15 (6.67%)
Skin and subcutaneous tissue disorders
Dermatitis diaper * 1	2/15 (13.33%)
Rash * 1	1/15 (6.67%)
Rash generalised * 1	1/15 (6.67%)
Rash macular * 1	1/15 (6.67%)
Seborrhoea * 1	1/15 (6.67%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (13.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

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.

Results Point of Contact

• Name/Title: Robert Winkler, MD, VP, Clinical Development and Operations
• Organization: Aptalis Pharma US, Inc.
• Phone: 1-800-472-2634

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01131507
• Other Study ID Numbers: PR-018
• First Submitted: May 25, 2010
• First Posted: May 27, 2010
• Results First Submitted: January 27, 2014
• Results First Posted: March 7, 2014
• Last Update Posted: March 21, 2017