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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Cystic Fibrosis, Exocrine Pancreatic Insufficiency

Intervention / Treatment
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* Drug: EUR-1008 (APT-1008)
* Drug: EUR-1008 (APT-1008)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EUR-1008 (APT-1008) in Apple Juice<br> | Drug: EUR-1008 (APT-1008)<br>* 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.<br>* Other names: Zenpep® (pancrelipase) delayed release capsules;|
| Experimental: EUR-1008 (APT-1008) in Apple Sauce<br> | Drug: EUR-1008 (APT-1008)<br>* 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.<br>* Other names: Zenpep® (pancrelipase) delayed release capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Difference for Acceptability of Treatment | 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). | Baseline up to end of study (Day 21) | 
| Question 6 (Previous Pancreatic Enzyme Product [PEP]) | 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. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Number of Stools | 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. | Up to Day 10 in first and second treatment periods, end of study (Day 21) | 
| Number of Stools Categorized as Per Consistency | 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. | Up to Day 10 in first and second treatment periods, end of study (Day 21) | 
| Number of Stools With Signs of Blood and Visible Oil or Grease | 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. | Up to Day 10 in first and second treatment periods, end of study (Day 21) | 
| Number of Abdominal Symptoms: Bloating | 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. | Up to Day 10 in first and second treatment periods, end of study (Day 21) | 
| Number of Abdominal Symptoms: Flatulence | 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. | Up to Day 10 in first and second treatment periods, end of study (Day 21) | 
| Number of Abdominal Pain Symptoms | 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. | Up to Day 10 in first and second treatment periods, end of study (Day 21) | 
| Number of Participants With Abnormal Clinical Laboratory and Vital Signs Findings |  | Baseline up to end of study (Day 21) | 
| Number of Participants With Abnormal Findings With Respect to Oral Mucosa | 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. | Baseline up to end of study (Day 21) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exocrine Pancreatic Insufficiency, Infants with CF