Naloxegol for Opioid-Related Gastroparesis

August 25, 2020 updated by: Temple University

Naloxegol for Opioid-Related Gastroparesis: A Double-Blind Study With an Open Label Extension

The objective of this study is to evaluate the effects of naloxegol (a peripheral mu-opioid receptor antagonist [PAMORA]) in opioid-related gastroparesis on 1) symptoms of gastroparesis; 2) gastric emptying; and 3) pain control. The endpoints will be gastroparesis symptoms (PAGI-SYM), gastric emptying (GEBT), and pain control (McGill Pain Inventory). The hypothesis to be tested is that naloxegol improves symptoms of gastroparesis in patients who are taking opioids as well as improves their gastric emptying while maintaining control of patient's pain. This study will entail an initial double-blind, randomized, placebo-controlled, 4-week treatment period of naloxegol vs placebo in patients with opioid-related gastroparesis followed by a 4-week open label period to demonstrate the improvement in symptoms and gastric emptying with naloxegol.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Medicines can delay gastric emptying and produce similar symptoms to gastroparesis. In particular, narcotic analgesics, can produce a gastroparesis picture, by delaying gastric emptying. The slowing effect of opioids on gastric, small bowel, and colonic motility has been well characterized. Unfortunately, many of these patients cannot stop their pain medications due to their underlying condition, such as back pain, fibromyalgia. On top of this, the narcotics can reduce the effectiveness of prokinetics agents used to treat gastroparesis, such as metoclopramide and domperidone. At this time, there is no good treatment for gastroparesis, especially for opioid-related gastroparesis.

Data suggests a relationship between opioid use and decreased gastric motility. Literature suggests that peripherally acting opioid agonist may provide relief in the instance of GI dysfunction (Holzer 2007). Movantik (Naloxegol) is an opioid agonist specifically designed to work outside of the central nervous system. Movantik (Naloxegol) can alleviate the adverse effects associated in chronic pain patients on opioid treatment - reduction of the undesired peripheral effects of opioids without disrupting analgesic effects. The use of Movantik (Naloxegol) has the potential to improve gastric dysmotility while preserving pain relief of the opioid analgesic.

The objective of this study is to evaluate the effects of naloxegol in opioid-related gastroparesis. This will be a randomized, double-blind study comparing Movantik 25 mg to placebo. The dose of Movantik is the dose that is currently FDA approved for opioid-induced constipation. The four-week study period is the duration of the phase 2b studies for Movantik for opioid-induced constipation in which the response rates were 60% and 35% with active treatment and placebo (Chey 2015).

The investigators have included a unique aspect of this study to better balance the benefits for patients participating in this randomized double-blind study in which half the patients receive a placebo agent. All patients in the treatment group and the placebo group will be invited to participate in the 4-week open-label extension for this study. This also serves to study the duration of the potential favorable effects of Movantik (Naloxegol) in this patient population as well as offering an extended time period to assess safety and tolerability.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Lewis Katz School of Medicine at Temple University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 84 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18-84, Males or Females
  2. Daily use of narcotic analgesics for treatment of pain. Patients need to be on a stable daily dose of opiates for the last 4 weeks prior to enrollment
  3. Patients with symptoms of gastroparesis with GCSI score (from the PAGI-SYM) of >2.0. These symptoms of gastroparesis must be present after starting opioid treatment.
  4. Delayed gastric emptying based on previous scintigraphy (Percent gastric retention >60% at 2 hours and/or >10% retention at 4 hours
  5. Signing informed consent prior to any study specific procedures

Exclusion Criteria:

  1. Prior gastric resective surgery such as bariatric surgery, antrectomy.
  2. Presence of severe renal impairment (CrCl<60 ml/min)
  3. Presence of severe hepatic impairment - Child-Pugh Classification Class C, generally AST>200 or ALT>200 or Total bilirubin >3.0.
  4. Other conditions besides gastroparesis that could potentially slow gastric emptying, such as untreated hypothyroidism.
  5. Concomitants use of strong CYP 3A4 inhibitors (such as ketoconazole, diltiazem, erythromycin, clarithromycin), use of CYP3A4 inducer.
  6. Use of NSAIDs and/or Plavix/Clopidogrel
  7. Any prior use of Movantik (the study drug) or other opioid receptor antagonist (e.g., Relistor (methylnaltrexone), naltrexone, or naloxone) before the screening visit.
  8. Patients with known cancer or cancer history within last 5 years prior to the screening visit.
  9. Patients with GI obstruction and/or perforation or conditions with potential for GI perforation.
  10. Patients with disruption to the blood-brain barrier;
  11. Current use of a medication affecting gastric motility such as metoclopramide, domperidone, and erythromycin;
  12. Pregnant women, females planning to become pregnant, and nursing mothers.
  13. Women of childbearing potential who are unwilling to use contraceptives throughout the course of treatment
  14. Subjects with severe co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, neurologic) based on PI's clinical judgment.
  15. Active substance abuse.
  16. History of major comorbid psychiatric conditions including mania and schizophrenia or severe current depression
  17. At-risk populations, including prisoners and mentally challenged. Any condition or the patient is in a situation which may put him/her at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study (e.g., difficulty hearing, cognitive impairment)
  18. Patients in which Movantik is clinically inadvisable
  19. Subject unable to consent or is unwilling to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study Group
Naloxegol 25 mg, oral tablet, daily for 4 weeks
Drug: Naloxegol 25 MG Oral Tablet [Movantik]
Patients will be given the study drug (Movantik 25 mg).They will take this daily in the morning 1 hour before breakfast for four weeks.
Other Names:
  • Study
Placebo Comparator: Placebo Control
Placebo Oral Tablet, 25 mg, oral tablet, daily for 4 weeks
Drug: Placebo Oral Tablet
Patients will be given Placebo (Placebo 25 mg).They will take this daily in the morning 1 hour before breakfast for four weeks.
Other Names:
  • Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gastric Emptying (GE t-1/2)
Time Frame: 4 week
Improvement in gastric emptying (GE t-1/2) compared to Placebo
4 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daily Symptom Improvement using the GCSI-DD (Gastroparesis Cardinal Symptom Index-Daily Diary)
Time Frame: 4 weeks
Improvements of gastroparesis symptoms using the GCSI-DD (Gastroparesis Cardinal Symptom Index-Daily Diary)
4 weeks
Symptom Improvement using PAGI-SYM
Time Frame: 4 weeks
Improvements of gastroparesis symptoms using PAGI-SYM
4 weeks
Pain Management using the McGill Pain Inventory
Time Frame: 4 weeks
Changes in pain control using the McGill Pain Inventory
4 weeks
Overall improvement in Gastric Emptying (GE t-1/2)
Time Frame: 8 week
Improvement in gastric emptying (GE t-1/2) compared to Placebo
8 week
Quality of Life based on SF-36
Time Frame: 4 weeks
QOL score changes based on SF-36
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Temple University

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Henry Parkman, MD, Temple University Hospita

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 29, 2016

Primary Completion (Actual)

September 30, 2019

Study Completion (Actual)

September 30, 2019

Study Registration Dates

First Submitted

January 27, 2017

First Submitted That Met QC Criteria

January 27, 2017

First Posted (Estimate)

January 30, 2017

Study Record Updates

Last Update Posted (Actual)

August 27, 2020

Last Update Submitted That Met QC Criteria

August 25, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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