Movantik for Opioid-Related Esophageal Disorders

• Status: Terminated
• Trial end date: 2018-10-01
• Target enrollment: 0
• Participant gender: All

Summary

To date, few studies have assessed the effect of opioids on esophageal motility, mostly assessed the effect of single-dose intravenous morphine on esophageal motility. Recently a large retrospective study assessing the effect of opioids on esophageal motility found that esophageal motor dysfunction are common in chronic opioid users whether studied on opioids and off opioids. In addition, current opioid users also had significantly higher integrated relaxation pressure and manometric patterns consistent with type III achalasia. (Ratuapli 2015) Peripherally acting mu opioid receptor antagonists (PAMORA) appear to be useful to reduce the peripheral effects of mu opioid receptor agonists to delay gastrointestinal transit without affecting the centrally mediated analgesic effects. MOVANTIK™ (Naloxegol) is the first oral peripherally acting mu opioid receptor antagonists for opioid-induced constipation. MOVANTIK™ (Naloxegol) has been recently approved for opioid-induced constipation. Given orally, 25 mg daily it improves symptoms of constipation. At this dose, MOVANTIK™ (Naloxegol) is effective and safe, with a limited side effect profile and is associated with preservation of centrally mediated analgesia.

This study will explore the safety and tolerability of MOVANTIK™ (Naloxegol) in this patient population.

The investigational hypothesis is that MOVANTIK™ (Naloxegol) could improve opioid- induced esophageal motility disorders

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

Details

• Lead Sponsor: Temple University
• Collaborator: AstraZeneca
• Treatments: Naloxegol

Criteria

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures

2. Age 18-85, Males and Females

3. On a stable daily opioid dose for various indications for at least 4 weeks prior to the HREM (High Resonance Esophageal Manometry

4. Symptoms of odynophagia, dysphagia, or chest pain based on symptoms recorded on the PAGI-SYM

Exclusion Criteria:

1. Renal impairment (cct<60) or severe Hepatic impairment as defined by the Child-Pugh Classification (Appendix J)

2. Concomitant use of strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, NSAIDS, Plavix/Clopidogrel and other opioid antagonists

3. History of GI obstruction, bowel perforation, or with potential for either based on investigator's clinical judgment

4. Subjects with known Barrett's esophagus or peptic stricture on endoscopy

5. Subjects with previous upper gastrointestinal surgery

6. Pregnant, plan to be pregnant, or are breastfeeding

7. Women of childbearing potential who are unwilling to use contraceptives throughout the course of treatment

8. Subjects with serious co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, neurologic) which may prevent the patient to participate in the study based on PI's clinical judgment or malignancy

9. Patients with an increased risk of gastrointestinal perforation due to conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g. peptic ulcer disease, Ogilvie's syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases).

10. Subjects with upper airway symptoms (such as hoarseness, wheezing or laryngospasm)

11. Patients taking baclofen or sucralfate and those unwilling to discontinue prohibited medications.

12. Known history of substance abuse

13. Subject unable to consent or is unwilling to provide informed consent

14. History of major comorbid psychiatric conditions including mania and schizophrenia or severe current depression

15. At-risk populations, including prisoners and mentally challenged. Any condition or 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)

16. Known allergy to MOVANTIK™ (Naloxegol)

17. Patients with a history of cancer within past 5 years prior to the screening visit

18. Patients with a medical condition which may disrupt the blood-brain barrier