Exocrine Pancreatic Insufficiency
Conditions
Brief summary
Protocol ALCT-0000497 is a multicenter safety, tolerability and fat absorption study that anticipates enrolling 35 male and female subjects (pediatric and adult) with cystic fibrosis. Subjects with confirmed exocrine pancreatic insufficiency will use a novel enteral feeding in-line digestive enzyme cartridge (RELiZORB) connected to enteral pump sets.
Detailed description
Protocol ALCT-0000497 consists of three distinct study periods as follows: 1. In Period A (7 days), subjects will receive Peptamen 1.5 enteral feedings at home. 2. In Period B (11 days), subjects will be randomized to either Group A (active investigational then placebo control) or Group B (placebo control then active investigational) and receive Impact Peptide 1.5 on Days 1 and 9. During the 8-day washout period between Days 1 and 9, subjects will receive Peptamen 1.5. 3. In Period C (9 days), subjects will use RELiZORB during nocturnal enteral feedings with Impact Peptide 1.5.
Interventions
DEVICERELiZORB
Peptamen 1.5 received Period A and Period B (washout only). Impact Peptide 1.5 received Period B (Days 1 and 9 only) and Period C.
DEVICEPlacebo
Sham device
Sponsors
Alcresta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed CF diagnosis with 2 clinical features 2. Documented history of EPI 3. Enteral formula use minimum of 4x/week 4. Written informed consent or assent, as applicable
Exclusion criteria
1. Uncontrolled diabetes mellitus 2. Signs and symptoms of liver cirrhosis or portal hypertension 3. Lung/liver transplant 4. Active cancer currently receiving cancer treatment 5. Crohn's or celiac disease, infectious gastroenteritis, sprue, lactose intolerant, inflammatory bowel disease 6. DIOS or fibrosing colonopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | 27 days | 1\) Frequency and severity of adverse events; 2) Patients with at least one unanticipated adverse device effects (UADE) |
| Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population) | Day 1 first intervention and Day 9 second intervention. | AUC analysis of plasma fatty acid concentration for DHA + EPA baseline adjusted over 24-hours |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ease of Use of RELiZORB (Per-Protocol Population) | Period C: Single assessment on Day 19 or 20 | Effect of enteral nutrition on select activities of daily living. Patients judged the size of breakfast after overnight enteral tube feeding with the following choices: No breakfast; Small breakfast; Normal breakfast; Big breakfast; Other. |
Countries
United States
Participant flow
Recruitment details
34 patients enrolled; 33 patients completed the study from 11 U.S. sites.
Pre-assignment details
33 eligible patients according to the inclusion/exclusion criteria were randomized in Period B (double-blind crossover) to the study.
Participants by arm
| Arm | Count |
|---|---|
| Clinical Treatment Practice: Period A: Days -7 to -1 Period A was a 7-day baseline period. Patients received Peptamen 1.5 at their normal volume of enteral formula administration up to a maximum of 1000 mL per feeding. Current treatment practice was followed with normal use of oral pancreatic enzyme replacement therapy (PERT) during daily meals and nightly enteral feedings. A gastrointestinal symptom diary was completed for 7 consecutive days. Baseline Day -7 required a clinic visit followed by Days -6 to -1 at home. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period A: Days -7 to -1 | Adverse Event | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Clinical Treatment Practice: Period A: Days -7 to -1 |
|---|---|
| Age, Categorical <=18 years | 27 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Baseline Body Mass Index | 17.47 kg/m^2 STANDARD_DEVIATION 2.026 |
| Baseline Height | 152.32 centimeters STANDARD_DEVIATION 19.64 |
| Baseline Weight | 41.81 kilograms STANDARD_DEVIATION 13.332 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 33 | 0 / 33 | 0 / 33 |
| serious Total, serious adverse events | 1 / 33 | 0 / 33 | 0 / 33 |
Outcome results
Primary
Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population)
AUC analysis of plasma fatty acid concentration for DHA + EPA baseline adjusted over 24-hours
Time frame: Day 1 first intervention and Day 9 second intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clinical Treatment Practice: Period A: Days -7 to -1 | Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population) | 536.98 ug*h/mL | Standard Deviation 400.519 |
| Crossover Period B: Placebo | Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population) | 192.18 ug*h/mL | Standard Deviation 198.664 |
p-value: <0.001Mixed Models Analysis
Primary
Number of Patients With Adverse Events and Unanticipated Adverse Device Effects
1\) Frequency and severity of adverse events; 2) Patients with at least one unanticipated adverse device effects (UADE)
Time frame: 27 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clinical Treatment Practice: Period A: Days -7 to -1 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Severe) | 0 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Mild) | 2 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With At Least One UADE | 0 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Moderate) | 2 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With Adverse Events | 4 Participants |
| Crossover Period B: Placebo | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Moderate) | 0 Participants |
| Crossover Period B: Placebo | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Severe) | 0 Participants |
| Crossover Period B: Placebo | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With At Least One UADE | 0 Participants |
| Crossover Period B: Placebo | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Mild) | 6 Participants |
| Crossover Period B: Placebo | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With Adverse Events | 6 Participants |
| Crossover Period B: RELiZORB | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Moderate) | 0 Participants |
| Crossover Period B: RELiZORB | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With Adverse Events | 1 Participants |
| Crossover Period B: RELiZORB | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Mild) | 1 Participants |
| Crossover Period B: RELiZORB | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Severe) | 0 Participants |
| Crossover Period B: RELiZORB | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With At Least One UADE | 0 Participants |
| Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Severe) | 1 Participants |
| Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Mild) | 0 Participants |
| Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With Adverse Events | 2 Participants |
| Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Adverse Event by Severity (Moderate) | 1 Participants |
| Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 | Number of Patients With Adverse Events and Unanticipated Adverse Device Effects | Patients With At Least One UADE | 0 Participants |
Other Pre-specified
Ease of Use of RELiZORB (Per-Protocol Population)
Effect of enteral nutrition on select activities of daily living. Patients judged the size of breakfast after overnight enteral tube feeding with the following choices: No breakfast; Small breakfast; Normal breakfast; Big breakfast; Other.
Time frame: Period C: Single assessment on Day 19 or 20
Population: Per Protocol Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clinical Treatment Practice: Period A: Days -7 to -1 | Ease of Use of RELiZORB (Per-Protocol Population) | No breakfast | 11 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Ease of Use of RELiZORB (Per-Protocol Population) | Small breakfast | 14 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Ease of Use of RELiZORB (Per-Protocol Population) | Normal breakfast | 6 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Ease of Use of RELiZORB (Per-Protocol Population) | Big breakfast | 0 Participants |
| Clinical Treatment Practice: Period A: Days -7 to -1 | Ease of Use of RELiZORB (Per-Protocol Population) | Other | 1 Participants |