Naloxegol for Opioid-Related Gastroparesis

• Status: Withdrawn
• Trial end date: 2019-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Temple University
• Collaborator: AstraZeneca
• Treatments: Analgesics, Opioid; Naloxegol

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