Trial Outcomes & Findings for Safety, Tolerability and Fat Absorption Using Enteral Feeding In-line Enzyme Cartridge (Relizorb) (NCT NCT02598128)

NCT ID: NCT02598128

Last Updated: 2017-01-25

Results Overview

1\) Frequency and severity of adverse events; 2) Patients with at least one unanticipated adverse device effects (UADE)

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 34 participants
• Primary outcome timeframe: 27 days
• Results posted on: 2017-01-25

Participant Flow

34 patients enrolled; 33 patients completed the study from 11 U.S. sites.

33 eligible patients according to the inclusion/exclusion criteria were randomized in Period B (double-blind crossover) to the study.

Participant milestones

Measure	Period A: Clinical Treatment Practice (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.	Crossover Period B: Placebo Then RELiZORB Eligible subjects were randomized to Placebo then RELiZORB.	Crossover Period B: RELiZORB Then Placebo Eligible subjects were randomized to RELiZORB then Placebo.	Period C: Clinical Treatment Practice + RELiZORB (Days 12-20) Period C was the open label clinical treatment period with RELiZORB. All patients used RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
Period A: Days -7 to -1 STARTED	34	0	0	0
Period A: Days -7 to -1 COMPLETED	33	0	0	0
Period A: Days -7 to -1 NOT COMPLETED	1	0	0	0
Period B: Days 1 to 11 STARTED	0	17	16	0
Period B: Days 1 to 11 COMPLETED	0	17	16	0
Period B: Days 1 to 11 NOT COMPLETED	0	0	0	0
Period C: Days 12 to 20 STARTED	0	0	0	33
Period C: Days 12 to 20 COMPLETED	0	0	0	33
Period C: Days 12 to 20 NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Measure	Period A: Clinical Treatment Practice (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.	Crossover Period B: Placebo Then RELiZORB Eligible subjects were randomized to Placebo then RELiZORB.	Crossover Period B: RELiZORB Then Placebo Eligible subjects were randomized to RELiZORB then Placebo.	Period C: Clinical Treatment Practice + RELiZORB (Days 12-20) Period C was the open label clinical treatment period with RELiZORB. All patients used RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
Period A: Days -7 to -1 Adverse Event	1	0	0	0

Baseline Characteristics

Baseline weight obtained in Period A.

Baseline characteristics by cohort

Measure	Clinical Treatment Practice: Period A: Days -7 to -1 n=33 Participants 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.
Age, Categorical <=18 years	27 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	33 Participants n=5 Participants
Baseline Weight	41.81 kilograms STANDARD_DEVIATION 13.332 • n=5 Participants • Baseline weight obtained in Period A.
Baseline Height	152.32 centimeters STANDARD_DEVIATION 19.640 • n=5 Participants • Baseline height obtained in Period A.
Baseline Body Mass Index	17.47 kg/m^2 STANDARD_DEVIATION 2.026 • n=5 Participants • Baseline Body Mass Index obtained in Period A.

PRIMARY outcome

Timeframe: 27 days

Population: Safety Population

1) Frequency and severity of adverse events; 2) Patients with at least one unanticipated adverse device effects (UADE)

Outcome measures

Measure	Clinical Treatment Practice: Period A: Days -7 to -1 n=33 Participants 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.	Crossover Period B: Placebo n=33 Participants Non-gastrointestinal adverse events during administration.	Crossover Period B: RELiZORB n=33 Participants Non-gastrointestinal adverse events during administration.	Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 n=33 Participants Non-gastrointestinal adverse events during CTP+RELiZORB administration.
Number of Patients With Adverse Events and Unanticipated Adverse Device Effects Patients With Adverse Events	4 Participants	6 Participants	1 Participants	2 Participants
Number of Patients With Adverse Events and Unanticipated Adverse Device Effects Adverse Event by Severity (Mild)	2 Participants	6 Participants	1 Participants	0 Participants
Number of Patients With Adverse Events and Unanticipated Adverse Device Effects Adverse Event by Severity (Moderate)	2 Participants	0 Participants	0 Participants	1 Participants
Number of Patients With Adverse Events and Unanticipated Adverse Device Effects Adverse Event by Severity (Severe)	0 Participants	0 Participants	0 Participants	1 Participants
Number of Patients With Adverse Events and Unanticipated Adverse Device Effects Patients With At Least One UADE	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1 first intervention and Day 9 second intervention.

AUC analysis of plasma fatty acid concentration for DHA + EPA baseline adjusted over 24-hours

Outcome measures

Measure	Clinical Treatment Practice: Period A: Days -7 to -1 n=33 Participants 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.	Crossover Period B: Placebo n=33 Participants Non-gastrointestinal adverse events during administration.	Crossover Period B: RELiZORB Non-gastrointestinal adverse events during administration.	Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 Non-gastrointestinal adverse events during CTP+RELiZORB administration.
Long Chain Polyunsaturated Fatty Acid Plasma Concentration (Intent to Treat Population)	536.98 ug*h/mL Standard Deviation 400.519	192.18 ug*h/mL Standard Deviation 198.664	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Period C: Single assessment on Day 19 or 20

Population: 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.

Outcome measures

Measure	Clinical Treatment Practice: Period A: Days -7 to -1 n=32 Participants 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.	Crossover Period B: Placebo Non-gastrointestinal adverse events during administration.	Crossover Period B: RELiZORB Non-gastrointestinal adverse events during administration.	Clinical Treatment Practice + RELiZORB: Period C: Days 12-20 Non-gastrointestinal adverse events during CTP+RELiZORB administration.
Ease of Use of RELiZORB (Per-Protocol Population) Other	1 Participants	—	—	—
Ease of Use of RELiZORB (Per-Protocol Population) No breakfast	11 Participants	—	—	—
Ease of Use of RELiZORB (Per-Protocol Population) Small breakfast	14 Participants	—	—	—
Ease of Use of RELiZORB (Per-Protocol Population) Normal breakfast	6 Participants	—	—	—
Ease of Use of RELiZORB (Per-Protocol Population) Big breakfast	0 Participants	—	—	—

Adverse Events

Clinical Treatment Practice: Period A: Days -7 to -1

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Double-Blind Crossover: Period B: Days 1 to 11

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Clinical Treatment Practice and Relizorb: Period C: Days 12-20

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Clinical Treatment Practice: Period A: Days -7 to -1 n=33 participants at risk 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.	Double-Blind Crossover: Period B: Days 1 to 11 n=33 participants at risk Period B was the randomized, double-blind, placebo-controlled crossover period. Eligible patients were randomized in a 1:1 ratio to either Placebo-RELiZORB or RELiZORB-Placebo treatment sequences. On two separate administration Days 1 and 9, patients received 500 mL of Impact Peptide1.5 in clinic over a 4h period. Motility and acid suppression medications were discontinued 24h before arrival in clinic. No nocturnal feeding occurred between Days 1-2 and Days 9-10. During the home washout period Days 2 to 8, patients received Peptamen 1.5 for enteral nutrition up to a maximum volume of 1000 mL per feeding. Safety follow up calls were conducted on Days 2 and 10.	Clinical Treatment Practice and Relizorb: Period C: Days 12-20 n=33 participants at risk Period C was the open label clinical treatment period with RELiZORB. All patients received RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
Infections and infestations Cystic fibrosis pulmonary exacerbation	3.0% 1/33 • Number of events 1 • 20 days Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)	0.00% 0/33 • 20 days Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)	0.00% 0/33 • 20 days Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)

Other adverse events

Measure	Clinical Treatment Practice: Period A: Days -7 to -1 n=33 participants at risk 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.	Double-Blind Crossover: Period B: Days 1 to 11 n=33 participants at risk Period B was the randomized, double-blind, placebo-controlled crossover period. Eligible patients were randomized in a 1:1 ratio to either Placebo-RELiZORB or RELiZORB-Placebo treatment sequences. On two separate administration Days 1 and 9, patients received 500 mL of Impact Peptide1.5 in clinic over a 4h period. Motility and acid suppression medications were discontinued 24h before arrival in clinic. No nocturnal feeding occurred between Days 1-2 and Days 9-10. During the home washout period Days 2 to 8, patients received Peptamen 1.5 for enteral nutrition up to a maximum volume of 1000 mL per feeding. Safety follow up calls were conducted on Days 2 and 10.	Clinical Treatment Practice and Relizorb: Period C: Days 12-20 n=33 participants at risk Period C was the open label clinical treatment period with RELiZORB. All patients received RELiZORB with Impact Peptide 1.5 at their normal volume as in Period A up to a maximum of 1000 mL per feeding. Patients were instructed to use the same daily dose and schedule of oral PERT taken in Period C as in Period A. There were no dietary restrictions. A gastrointestinal symptom diary was completed for 7 consecutive days. Patients received enteral feeding at home from Days 12 to 18 and returned to clinic for their end of study Day 19.
Nervous system disorders Headache	6.1% 2/33 • Number of events 3 • 20 days Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)	0.00% 0/33 • 20 days Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)	0.00% 0/33 • 20 days Safety Population: Non-gastrointestinal Adverse Event by System Organ Class and Preferred Term (n=33)

Additional Information

Russell G. Clayton, D.O., Chief Medical Officer

Alcresta Therapeutics, Inc.

Phone: 215.813.5100

Email: rclayton@alcresta.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60