Cystic Fibrosis, Exocrine Pancreatic Insufficiency
Conditions
Keywords
Exocrine Pancreatic Insufficiency, Infants with CF
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).
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.
Interventions
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.
Sponsors
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | EUR-1008 (APT-1008) |
|---|---|
| Age, Continuous | 9.0 months FULL_RANGE 3.27 |
| Length | 68.5 centimeter FULL_RANGE 5.98 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
| Weight | 7.80 kilogram FULL_RANGE 1.296 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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
Population: Safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Possibly related TEAEs | 4 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Probably related TEAEs | 1 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Mild TEAEs | 5 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 15 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | SAEs | 3 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Unrelated TEAEs | 10 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Moderate TEAEs | 8 participants |
| EUR-1008 (APT-1008) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Severe TEAEs | 2 participants |
Secondary
Change From Baseline in Growth Percentiles at 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.
Time frame: Baseline, Month 3, 6, 9 and 12
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-age: Baseline (n=15) | 22.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Length-for-age: Change at Month 12 (n=12) | 0.5 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-length: Baseline (n=14) | 41.5 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-length: Change at Month 3 (n=14) | 0.5 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-age: Change at Month 3 (n=15) | 2.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-age: Change at Month 6 (n=13) | 6.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-age: Change at Month 9 (n=12) | 4.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-age: Change at Month 12 (n=12) | 5.5 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Length-for-age: Baseline (n=14) | 36.5 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Length-for-age: Change at Month 3 (n=14) | 2.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Length-for-age: Change at Month 6 (n=12) | 2.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Length-for-age: Change at Month 9 (n=12) | 11.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-length: Change at Month 6 (n=12) | 13.5 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-length: Change at Month 9 (n=12) | 9.0 growth percentile |
| EUR-1008 (APT-1008) | Change From Baseline in Growth Percentiles at Month 3, 6, 9 and 12 | Weight-for-length: Change at Month 12 (n=12) | 10.5 growth percentile |