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Naloxegol for Opioid-Related Gastroparesis

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ClinicalTrials.gov Identifier: NCT03036891
Recruitment Status : Recruiting
First Posted : January 30, 2017
Last Update Posted : February 4, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Temple University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastroparesis Opioid Use Drug: Naloxegol 25 MG Oral Tablet [Movantik] Drug: Placebo Oral Tablet Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Naloxegol for Opioid-Related Gastroparesis: A Double-Blind Study With an Open Label Extension
Actual Study Start Date : December 29, 2016
Estimated Primary Completion Date : January 30, 2020
Estimated Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Naloxegol

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 Name: 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 Name: Control




Primary Outcome Measures :
  1. Gastric Emptying (GE t-1/2) [ Time Frame: 4 week ]
    Improvement in gastric emptying (GE t-1/2) compared to Placebo


Secondary Outcome Measures :
  1. 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)

  2. Symptom Improvement using PAGI-SYM [ Time Frame: 4 weeks ]
    Improvements of gastroparesis symptoms using PAGI-SYM

  3. Pain Management using the McGill Pain Inventory [ Time Frame: 4 weeks ]
    Changes in pain control using the McGill Pain Inventory

  4. Overall improvement in Gastric Emptying (GE t-1/2) [ Time Frame: 8 week ]
    Improvement in gastric emptying (GE t-1/2) compared to Placebo

  5. Quality of Life based on SF-36 [ Time Frame: 4 weeks ]
    QOL score changes based on SF-36



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03036891


Contacts
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Contact: Henry Parkman, MD 2157077579 henry.parkman@tuhs.temple.edu
Contact: Kelly King, MPH 215-707-2498 kelly.king@tuhs.temple.edu

Locations
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United States, Pennsylvania
Lewis Katz School of Medicine at Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Henry Parkman, MD    215-707-7579    henry.parkman@tuhs.temple.edu   
Contact: Kelly King, MPH    215-707-2498    kelly.king@tuhs.temple.edu   
Sponsors and Collaborators
Temple University
AstraZeneca
Investigators
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Principal Investigator: Henry Parkman, MD Temple University Hospita

Publications:

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Responsible Party: Temple University
ClinicalTrials.gov Identifier: NCT03036891     History of Changes
Other Study ID Numbers: 24102
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Temple University:
Gastroparesis
Opioid-Induced
Delayed Gastric Emptying

Additional relevant MeSH terms:
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Gastroparesis
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms
Analgesics, Opioid
Naloxegol
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists