RELiZORB is proven in clinical studies to break down fats in enteral formula Skip to content

RELiZORB is proven in clinical studies to break down fats in enteral formula

497 study: randomized, double-blind, and placebo-controlled study for safety and efficacy1


The 497 study is a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over study conducted to study the safety, tolerability, and fat absorption using RELiZORB in patients with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). Thirty-four screened patients were enrolled as participants in the study: 1 withdrew after hospitalization for pulmonary exacerbation, 1 withdrew after initially receiving the incorrect formula but re-enrolled; 33 were randomized and completed the study. Patients were ages 5-34 with CF-associated EPI, receiving supplemental enteral nutrition.

The study was broken into 3 periods with impact questionnaires before and after the study:

  • Period A: 7 day safety run-in period with PERT + Peptamen 1.5.
  • Period B: 9 day double-blind crossover treatment period. Treatment was conducted at day 1 and day 9 with Impact Peptide 1.5 + alternating RELiZORB or placebo with a 7-day washout period to allow DHA/EPA levels to return to baseline. Blood draws on day 1 and day 9 were taken at 0, 1, 3, 7, 9, 12, and 24 hours.
  • Period C: 7 day safety open-label period with RELiZORB + PERT + Impact Peptide 1.5.

The primary study endpoints measured were change in fatty acid plasma concentration of DHA and EPA and GI symptoms.

Changes in plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with RELiZORB1

Chart of changes in plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with RELiZORB

2.8-fold overall increase in total DHA and EPA with RELiZORB versus placebo (AUC0-24h; P<0.001)1

Use of RELiZORB was shown to normalize plasma concentrations of DHA and EPA1

DHA and EPA were used as measures in the studies as they are strongly correlated with overall fat absorption.2

With digestive cartridge use, plasma concentrations of total DHA + EPA from 7 through 24 hours were consistent with concentrations found in healthy humans.1

Decreased frequency of gastrointestinal (GI) symptoms with RELiZORB1

In the 497 study, overall the frequency of GI events decreased among 33 pediatric and adult patients with CF*

During Period C of the trial, 42% (n=14) of patients using RELiZORB stopped taking pancreatic enzyme replacement therapy (PERT) capsules, despite protocol instructions to maintain their usual treatment practice.

*GI events are expressed as: number of events (number of patients reporting events).

>50% of patients reported a decrease in the frequency of some GI events1

RELiZORB vs. PERTs alone: see the GI symptom comparison data1

OVERALL (n=33) PERT
(Period A)
PERT + RELiZORB
(Period C)
ABDOMINAL PAIN 29 (13) 19 (10)
BLOATING 14 (5) 7 (3)
CONSTIPATION 8 (6) 0 (0)
DIARRHEA 7 (7) 3 (3)
GAS 30 (12) 38 (10)
INDIGESTION / HEARTBURN 9 (6) 4 (3)
NAUSEA 9 (6) 6 (4)
STEATORRHEA / FATTY STOOL 7 (6) 7 (3)
VOMITING 4 (3) 5 (3)
FLATULENCE 1 (1) 7 (1)
SMELLY BURPS 4 (1) 0 (0)
LARGE VOLUME STOOL 0 (0) 4 (2)
ABDOMINAL GAS PAIN 0 (0) 1 (1)
TOTAL FREQUENCY 122 101

Overall the frequency of GI events decreased in Period C compared with Period A among 33 pediatric and adult patients with cystic fibrosis. Period A=baseline run-in period. Period C=open-label safety period. Gastrointestinal events are expressed as: number of events (number of patients reporting events).


ASSURE study: absorption & safety with sustained use3


The ASSURE study is a multicenter, 90-day open-label study during which RELiZORB was used with overnight enteral nutrition to study change over time in red blood cell (RBC) uptake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in patients with cystic fibrosis (CF). A total of 36 subjects completed the study with a mean age of 13.8 years, body mass index (BMI) of 17.7 and 6.2 years mean use of overnight enteral nutrition.

The study was broken into 3 periods:

  • Observation period: 7 days of PERT + usual enteral regimen.
  • Run-in period: 7 days of PERT + Peptamen 1.5.
  • Open-label treatment period: 90 days of RELiZORB + Impact Peptide 1.5.

The primary study endpoints measured were change over time in red blood cell uptake of DHA and EPA and GI symptoms.
Visit assessments measuring height; weight; BMI; vital signs; blood lipids; serum proteins; fatty acid levels; vitamins A, D, and E; AE; and UADE assessments were taken at days 0, 30, 60, and 90.

Increase in red blood cells of DHA and EPA with RELiZORB3

Chart of increase in red blood cells of DHA and EPA with RELiZORB

2.1-fold increase in red blood cells of DHA and EPA3

Statistically significant increases observed at Day 30, Day 60 and Day 90 (P<0.001 for each)

In the ASSURE study, longer-term and sustained use of RELiZORB with regular overnight enteral nutrition normalized plasma omega-3 levels consistent with a reference range based on healthy subjects. Levels were maintained over longer periods, indicating an improvement in fat malabsorption.

Improvement in weight percentiles with RELiZORB3

Overall, weight and body mass index (BMI) z-scores and percentiles were not significantly different from baseline to 90 days. However, 20/33 (61%) patients had improvement in weight z-scores and percentiles in the intention to treat (ITT) population. All exploratory efficacy outcomes, including serum levels of fat-soluble vitamins A, D, and E in plasma, as well as serum protein (total protein, prealbumin, albumin, and transferrin) levels, were within normal ranges at study entry and remained so throughout the 90-day study treatment period.

In the ASSURE study, usage of RELiZORB showed:

  • No reported incidences of diarrhea at Day 90
  • Overall, the number of participants reporting GI symptoms decreased from Day 30 to Day 90
  • RELiZORB is well-tolerated, no participants discontinued RELiZORB due to an adverse event

61% of participants demonstrated improvement in weight percentiles3

RELiZORB is proven to hydrolyze available fats,* including medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs).4

  • The iLipase in RELiZORB is intended to selectively break down triglycerides at the sn-1 and sn-3 positions.
  • LCTs are complex and contain essential fatty acids. Compared to MCTs, LCTs are harder to hydrolyze5 and provide ~10% more calories.4
>90% fat hydrolysis* with RELiZORB - Freedman

cartridge

cartridge

*Greater than 90% of available fats hydrolyzed in most enteral formulas tested, including Nutren 1.5, Impact Peptide 1.5, Peptamen 1.5, Peptamen AF, and Nutren 1.0. Percentage of fat hydrolysis is estimated based on label claim for content, calculated using 500 mL of formula with a pump rate of 120 mL/hr. Please see full list of compatible formulas.

References
  1. Freedman S, Orenstein D, Black P, et al. Increased fat absorption from enteral formula through an in-line digestive cartridge in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2017;65(1):97-101.
  2. Harris WS, Sands SA, Windsor SL, et al. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation 2004;110:1645-1649.
  3. Stevens J, Wyatt C, Brown P, Patel D, Grujic D, Freedman SD. Absorption and Safety with Sustained Use of RELiZORB Evaluation (ASSURE) study in patients with cystic fibrosis receiving enteral feeding. J Pediatr Gastroenterol Nutr. 2018;Oct;67(4):527-532.
  4. Freedman S. Options for Addressing Exocrine Pancreatic Insufficiency in Patients Receiving Enteral Nutrition Supplementation. Am J Manag Care. 2017 Jul;23(12 Suppl):S220-S228.
  5. Shah ND, Limketkai BN. The Use of Medium-Chain Triglycerides in Gastrointestinal Disorders. Practical Gastroenterology. 2017 Feb;41(2):20-28.