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

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Enteral Feeding Intolerance (EFI)

Intervention / Treatment
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* Drug: Ulimorelin
* Drug: Metoclopramide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Ulimorelin | Drug: Ulimorelin<br>* Active<br>|
| Active Comparator: Comparator<br>Metoclopramide | Drug: Metoclopramide<br>* Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |