Efficacy, Safety, and Pharmacokinetics (PK) Study of Ulimorelin in Patients With Enteral Feeding Intolerance (EFI): The PROMOTE Trial (PROMOTE)

A Phase 2, Multicenter, Randomized, Double-Blind, Comparator-Controlled Study of the Efficacy, Safety, and Pharmacokinetics of Intravenous Ulimorelin (LP101) in Patients With Enteral Feeding Intolerance (EFI)

The purpose of this study is to evaluate the effect Ulimorelin in patients with enteral feeding intolerance.

Study Overview

• Status: Completed
• Conditions: Enteral Feeding Intolerance (EFI)
• Intervention / Treatment: Drug: Ulimorelin; Drug: Metoclopramide

Detailed Description

This is a multicenter, randomized, double-blind, comparator-controlled study. The study consists of 2 parallel-dose treatment groups consisting of ulimorelin and metoclopramide. Approximately 120 mechanically ventilated, tube-fed patients with EFI will participate in this trial. To be eligible for study participation, the patients must be intolerant to continuous gastric tube feedings, with intolerance defined as having a gastric residual volume (GRV) of ≥ 500 mL on one or more measurements.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
• Spain
  • Barcelona, Spain
  • Madrid, Spain
• United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Ohio
    • Columbus, Ohio, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and non-pregnant women aged 18 years and above
• Intubated and mechanically ventilated in the ICU
• Receiving continuous nasogastric, orogastric, or percutaneous gastric tube feeding, with no contraindication to advancing feedings per the feeding protocol
• A 12-Fr or larger nasogastric, orogastric, or percutaneous gastric feeding tube, with its distal tip at least 10 cm below the gastroesophageal junction and visible in the stomach on a routine radiographic examination within 24 hours of screening
• Enteral feeding intolerance, defined as a GRV of ≥ 500 mL on one or more measurements Expected to remain intubated, mechanically ventilated, and receiving nasogastric feeding for at least 72 hours

Exclusion Criteria:

• Inability to obtain written informed consent to participate in the study from the patient or legally authorized representative
• Prior use during the current ICU admission of parenteral nutrition or trophic feeding, defined as a prescription to receive ≤ 20 mL/hr of enteral feeding for more than 24 hours prior to screening [N.B., parenteral nutrition may be initiated post randomization provided that the supplemental nutrition is coordinated with the calories and protein targets of the Prescribed Total Volume (PTV) and reduced as enteral feeding is advanced]
• Weight prior to ICU admission exceeding 150.0 kg
• Suspicion or confirmation of active bowel obstruction, perforation, or leakage
• History of esophageal or gastric surgery prior to or during the current hospital admission
• Use of any of the following prokinetic medications during the current ICU admission: domperidone, cisapride, neostigmine, or opioid antagonists, including alvimopan, naloxone, naltrexone, or analogs of naloxone or naltrexone; erythromycin or azithromycin [N.B., azithromycin is permitted for treatment of pulmonary infections up to 48 hours before randomization, but not thereafter through Day 5. Up to 2 doses of metoclopramide are permitted, provided that drug is not administered within 10 hours of the first dose of study drug or at any time through Day 5. If a patient receives metoclopramide during the screening period, a radiologic examination must confirm that the feeding tube remains visible in the stomach after the final dose of drug during screening and to prior to the start of baseline gastric emptying measurements and has not migrated to the duodenum. Use of clarithromycin for any indication is not excluded. Propofol must be discontinued before screening. However, its use may be permitted under special circumstances subsequent to the first dose of study drug but not in excess of 12 hours administration over the 5-day study period.]
• Patient's clinical condition is deteriorating rapidly, or the Investigator does not consider there to be a reasonable expectation that the patient will complete the study Childs C cirrhosis or Alanine Aminotransferase (ALT) ≥1000 U/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active; Ulimorelin	Drug: Ulimorelin; Active
ACTIVE_COMPARATOR: Comparator; Metoclopramide	Drug: Metoclopramide; Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The daily average (mean) percentage of target daily protein received through enteral nutrition by mechanically ventilated and tube-fed patients with EFI, Days 1 through 5	5 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
The daily average (mean) percentage of target daily calories received through enteral nutrition by mechanically ventilated and tube-fed patients with EFI, Days 1 through 5	5 Days

Other Outcome Measures

Outcome Measure	Time Frame
Serious Adverse Events (SAEs) and Adverse Events (AEs), summarized by treatment group and Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) and preferred term.	8 days
Clinical laboratory tests, summarized by treatment group	6 days
Electrocardiogram (ECGs), summarized by treatment group	5 days

Collaborators and Investigators

• Sponsor: Lyric Pharmaceuticals
• Investigators: Study Director: M Scott Harris, MD, Lyric Pharmaceuticals

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2016
• Primary Completion (ACTUAL): March 1, 2018
• Study Completion (ACTUAL): March 1, 2018

Study Registration Dates

• First Submitted: May 23, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (ESTIMATE): May 27, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Metoclopramide
• Other Study ID Numbers: LP101-CL-201; 2016-000723-94 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED