A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age

• ClinicalTrials.gov Identifier: NCT01100606
• Recruitment Status: Completed
• First Posted: April 9, 2010
• Results First Posted: April 10, 2014
• Last Update Posted: April 10, 2014
• Sponsor: Forest Laboratories
• Information provided by (Responsible Party): Forest Laboratories

Tracking Information

• First Submitted Date: March 31, 2010
• First Posted Date: April 9, 2010
• Results First Submitted Date: March 5, 2014
• Results First Posted Date: April 10, 2014
• Last Update Posted Date: April 10, 2014
• Study Start Date: June 2010
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 5, 2014)

• Treatment Difference for Acceptability of Treatment [ Time Frame: Baseline up to end of study (Day 21) ]
  Acceptability questionnaire consists of 9 question (Q) to assess ease, time, overall satisfaction of study drug. Rated on 5-point scale for Q1-Q5 and Q7-Q9; Q6 was not rated and asked for name of previous PEP administered. Q1=overall ease of administration (1=not at all easy,2=somewhat,3=easy,4=very,5=extremely); Q2=time of administration (1=very short[<2 min],2=short[2-5 min],3=moderate[5-15 min],4=long[15-25 min],5=very long[>25 min]);Q3=overall infant acceptance(1=very easily,2=easily,3=same,4=with difficulty,5=with great difficulty);Q4=clear/complete instructions(1=not clear,2=somewhat,3=clear,4=very,5=extremely);Q5=overall satisfaction with dosing method (1=not satisfied,2=somewhat,3=satisfied,4=very,5=extremely);Q7=comparative ease of administration (1=much worse,2=worse,3=same,4=better,5=much better);Q8=comparative infant acceptance (1=much more difficult,2=more,3=same,4=easier,5=much easier);Q9=comparative overall satisfaction (1=much less,2=less,3=same,4=more,5=much more).
• Question 6 (Previous Pancreatic Enzyme Product [PEP]) [ Time Frame: Baseline ]
  Acceptability questionnaire consists of 9 questions (Q) to assess the ease, time, overall satisfaction of study drug. Q6 included "name of previous PEP administered". Q6 was reported as number of participants who used any PEP prior to screening.

Original Primary Outcome Measures (submitted: April 7, 2010)

Acceptability of Treatment Administration Method [ Time Frame: up to 30 days ]

Tolerability measured by the acceptability of the treatment administration method. Measurement based on completed questionnaires in which caregiver's rate the ease of treatment administration, time to complete treatment administration and overall satisfaction with treatment administration on a scale of 1 to 5.

Current Secondary Outcome Measures (submitted: March 5, 2014)

• Daily Number of Stools [ Time Frame: Up to Day 10 in first and second treatment periods, end of study (Day 21) ]
  Average daily number of stools of each participant was calculated from frequency of stools by the participant per day. Average daily number of stools during the first treatment period, second treatment period and end of study for total participants was summarized.
• Number of Stools Categorized as Per Consistency [ Time Frame: Up to Day 10 in first and second treatment periods, end of study (Day 21) ]
  Stool consistency was categorized as hard, formed/normal, soft and diarrhea. Average number of stools categorized as per consistency of each participant was calculated from number of stools of specific consistency by the participant per day. Average number of stools categorized as per consistency during the first treatment period, second treatment period and end of study for total participants was summarized.
• Number of Stools With Signs of Blood and Visible Oil or Grease [ Time Frame: Up to Day 10 in first and second treatment periods, end of study (Day 21) ]
  Average number of stools with signs of blood and visible oil or grease of each participant was calculated from number of stools with signs of blood and visible oil or grease by the participant per day. Average number of stools with signs of blood and visible oil or grease during the first treatment period, second treatment period and end of study for total participants was summarized.
• Number of Abdominal Symptoms: Bloating [ Time Frame: Up to Day 10 in first and second treatment periods, end of study (Day 21) ]
  Bloating is swelling of the intestinal tract caused by excessive gas formation. Symptoms of bloating were classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the first treatment period, second treatment period and end of study for total participants was summarized.
• Number of Abdominal Symptoms: Flatulence [ Time Frame: Up to Day 10 in first and second treatment periods, end of study (Day 21) ]
  Flatulence is presence of excessive gas in the digestive tract. Symptoms of flatulence were classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the first treatment period, second treatment period and end of study for total participants was summarized.
• Number of Abdominal Pain Symptoms [ Time Frame: Up to Day 10 in first and second treatment periods, end of study (Day 21) ]
  Symptoms of pain was classified by severity as 0=none, 1=mild (no impairment of daily activities), 2=moderate (slight impairment of daily activities), and 3=severe (unable to perform daily activities). Average number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Average number of symptoms during the first treatment period, second treatment period and end of study for total participants was summarized.
• Number of Participants With Abnormal Clinical Laboratory and Vital Signs Findings [ Time Frame: Baseline up to end of study (Day 21) ]
• Number of Participants With Abnormal Findings With Respect to Oral Mucosa [ Time Frame: Baseline up to end of study (Day 21) ]
  Safety assessed by the presence of lesions observed during a physical examination at each visit. Severity of lesions measured by investigator's assessment using the following scale: mild = asymptomatic or mild symptoms and treatment not indicated; moderate = moderate pain but not interfering with oral intake, modified diet indicated; severe = severe pain, interfering with oral intake and life threatening or fatal.

Original Secondary Outcome Measures (submitted: April 7, 2010)

• Effects of treatment on the oral mucosa [ Time Frame: up to 30 days ]
  Safety assessed by the presence of lesions observed during a physical exams at each visit. Severity of lesions measured by investigator's assessment using the following scale: Mild = asymptomatic or mild symptoms; intervention not indicated; Moderate = moderate pain; not interfering with oral intake, modified diet indicated; Severe = severe pain, interfering with oral intake and life threatening or fatal.
• Changes in clinical laboratory results [ Time Frame: up to 30 days ]
  Safety evaluated by treatment differences in results collected from standard of care laboratory assessments.
• Presence of the signs and symptoms of Exocrine Pancreatic Insufficiency (EPI) [ Time Frame: up to 30 days ]
  Efficiacy mesured by the treatment differences in clinical signs and symptoms of Exocrine Pancreatic Insufficiency (EPI. This will be done based upon reported diary entries of signs and symptoms of EPI. Specifically measuring stool consistency(soft to hard), Presence of blood, oil or grease in the stool, and abdominal pain, bloating and gas measured on a scale of 0 to 3.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
• Official Title: 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)
• Brief Summary: A study to determine the safety, effectiveness, and acceptability of 2 methods of administration of EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) 3,000 lipase units capsule, a pancreatic enzyme product (PEP), in infants with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). This study is sponsored by Aptalis Pharma (formerly Eurand).

Detailed Description

This is a multicenter, randomized, open-label, crossover study in pediatric participants with EPI due to CF. The study will be carried out in infants between 1 and 12 months of age.

The study comprises of a screening period (up to 10 days) followed by 2 treatment periods (10 days each). During the screening period, all participants will be administered Zenpep® 5,000 (pancrelipase) mixed with a small amount of apple sauce. Once determined eligible for participation, participants will be randomized into 1 of 2 treatment sequences. Each sequence corresponds to taking one treatment in the first period and the other treatment in the second period, and were administered EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) 3,000 lipase units capsule either mixed with apple juice using a syringe nurser or apple sauce using a spoon.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cystic Fibrosis
• Exocrine Pancreatic Insufficiency

Intervention

• Drug: EUR-1008 (APT-1008)
  EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple juice, will be given orally daily using a syringe nurser at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period. Total dose will not exceed 10,000 lipase units per kilogram (kg) of body weight per day.
  Other Name: Zenpep® (pancrelipase) delayed release capsules
• Drug: EUR-1008 (APT-1008)
  EUR-1008 (APT-1008) (Zenpep® [pancrelipase] delayed release capsule) from open capsule, mixed with a small amount of apple sauce, will be given orally daily using a spoon at dose increments of 3,000 lipase units, for 10 days in either first treatment period or second treatment period. Total dose will not exceed 10,000 lipase units per kg of body weight per day.
  Other Name: Zenpep® (pancrelipase) delayed release capsules

Study Arms

• Experimental: EUR-1008 (APT-1008) in Apple Juice
  Intervention: Drug: EUR-1008 (APT-1008)
• Experimental: EUR-1008 (APT-1008) in Apple Sauce
  Intervention: Drug: EUR-1008 (APT-1008)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 13, 2011): 15
• Original Estimated Enrollment (submitted: April 7, 2010): 12
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants with diagnosis of CF based on the following criteria: one clinical feature consistent with CF, and either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration that is greater than 60 milliequivalent per liter by quantitative pilocarpine iontophoresis
• Participants who have the need for a PEP defined as monoclonal fecal elastase less than 200 microgram per gram (mcg/g) stool
• Caregiver must be willing to switch participant from their previous PEP (if any) to Zenpep®
• Participants who have a height to weight ratio target at greater than tenth percentile
• Participants who are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection during the 7-day interval prior to screening and preceding accession into this clinical study

Exclusion Criteria:

• Participants who are less than 1 month old or are greater than 12 months old
• Participants with history of meconium ileus or small bowel atresia in the newborn period that required surgery
• Participants who are allergic to pork or other porcine PEPs
• Participants with any respiratory condition or other serious comorbidity (for example patent ductus arteriosus [PDA], or necrotizing enterocolitis [NEC]) that in the investigator's opinion would result in an intervention requiring hospitalization or intensive pulmonary or other treatment during the trial
• Participants with other comorbidities independent of CF that, in the investigator's opinion, would result in an inability to participate in the study or excess risk to the participant that is above the standard of care
• Participants with acute respiratory infection in the previous 14 days requiring antibiotics
• Participants who required change in antacid dose in the 7 days before screening
• Participants with administration of oral, intramuscular (IM), intravenous (IV) glucocorticoids in the 4 weeks prior to screening
• Participants with any condition that would, in the investigator's opinion, limit the participant's ability to complete the study
• Participants currently participating in or has participated in an investigational study, with the exception of observational studies, within 30 days of the screening visit

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month to 12 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01100606
• Other Study ID Numbers: PR-011
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Forest Laboratories
• Original Responsible Party: Manager of Clinical Development and Operations, Eurand Pharmaceuticals, Inc.
• Current Study Sponsor: Forest Laboratories
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Aptalis Medical Information; Forest Laboratories

• PRS Account: Forest Laboratories
• Verification Date: March 2014