NCT02998606

Brief 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

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2017

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 14, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 20, 2016

Completed
12 days until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2018

Completed
Last Updated

December 24, 2018

Status Verified

December 1, 2018

Enrollment Period

1.7 years

First QC Date

December 14, 2016

Last Update Submit

December 20, 2018

Conditions

Opioid-Induced DisordersEsophagus Disorder

Outcome Measures

Primary Outcomes (1)

  • Manometric improvement in IRP (Integrated Relaxation Pressure)

    The effect of MOVANTIK™ (Naloxegol) on motor function, categorized as a 25% (mmHg) improvement in IRP (Integrated Relaxation Pressure) on high resolution esophageal manometry from baseline to visit three, comparing study group to placebo control group.

    28 days

Secondary Outcomes (7)

  • Overall Symptom Management

    28 days

  • Pain Management

    28 days

  • GERD Symptom Management

    28 days

  • Chest Pain Management

    28 days

  • Daily Symptom Management

    28 days

  • +2 more secondary outcomes

Study Arms (2)

Study Group

EXPERIMENTAL

MOVANTIK™ (Naloxegol) 25 mg oral capsule, daily

Drug: Naloxegol

Control Group

PLACEBO COMPARATOR

Placebo Oral Capsule 25 mg, daily

Drug: Placebo Oral Capsule

Interventions

NaloxegolDRUG

MOVANTIK™ 25 mg, daily

Also known as: Movantik
Study Group
Placebo Oral CapsuleDRUG

Placebo 25 mg, daily

Also known as: Placebo
Control Group

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of informed consent prior to any study specific procedures
  • Age 18-85, Males and Females
  • On a stable daily opioid dose for various indications for at least 4 weeks prior to the HREM (High Resonance Esophageal Manometry
  • Symptoms of odynophagia, dysphagia, or chest pain based on symptoms recorded on the PAGI-SYM

You may not qualify if:

  • Renal impairment (cct\<60) or severe Hepatic impairment as defined by the Child-Pugh Classification (Appendix J)
  • Concomitant use of strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, NSAIDS, Plavix/Clopidogrel and other opioid antagonists
  • History of GI obstruction, bowel perforation, or with potential for either based on investigator's clinical judgment
  • Subjects with known Barrett's esophagus or peptic stricture on endoscopy
  • Subjects with previous upper gastrointestinal surgery
  • Pregnant, plan to be pregnant, or are breastfeeding
  • Women of childbearing potential who are unwilling to use contraceptives throughout the course of treatment
  • 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
  • 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).
  • Subjects with upper airway symptoms (such as hoarseness, wheezing or laryngospasm)
  • Patients taking baclofen or sucralfate and those unwilling to discontinue prohibited medications.
  • Known history of substance abuse
  • Subject unable to consent or is unwilling to provide informed consent
  • History of major comorbid psychiatric conditions including mania and schizophrenia or severe current depression
  • 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)
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Related Publications (10)

  • Holzer P. Treatment of opioid-induced gut dysfunction. Expert Opin Investig Drugs. 2007 Feb;16(2):181-94. doi: 10.1517/13543784.16.2.181.

    PMID: 17243938BACKGROUND

  • Ratuapli SK, Crowell MD, DiBaise JK, Vela MF, Ramirez FC, Burdick GE, Lacy BE, Murray JA. Opioid-Induced Esophageal Dysfunction (OIED) in Patients on Chronic Opioids. Am J Gastroenterol. 2015 Jul;110(7):979-84. doi: 10.1038/ajg.2015.154. Epub 2015 Jun 2.

    PMID: 26032150BACKGROUND

  • Mittal RK, Frank EB, Lange RC, McCallum RW. Effects of morphine and naloxone on esophageal motility and gastric emptying in man. Dig Dis Sci. 1986 Sep;31(9):936-42. doi: 10.1007/BF01303214.

    PMID: 3731985BACKGROUND

  • Penagini R, Bartesaghi B, Zannini P, Negri G, Bianchi PA. Lower oesophageal sphincter hypersensitivity to opioid receptor stimulation in patients with idiopathic achalasia. Gut. 1993 Jan;34(1):16-20. doi: 10.1136/gut.34.1.16.

    PMID: 8381758BACKGROUND

  • Penagini R, Picone A, Bianchi PA. Effect of morphine and naloxone on motor response of the human esophagus to swallowing and distension. Am J Physiol. 1996 Oct;271(4 Pt 1):G675-80. doi: 10.1152/ajpgi.1996.271.4.G675.

    PMID: 8897888BACKGROUND

  • Dowlatshahi K, Evander A, Walther B, Skinner DB. Influence of morphine on the distal oesophagus and the lower oesophageal sphincter--a manometric study. Gut. 1985 Aug;26(8):802-6. doi: 10.1136/gut.26.8.802.

    PMID: 4018646BACKGROUND

  • Penagini R, Bianchi PA. Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation. Gastroenterology. 1997 Aug;113(2):409-14. doi: 10.1053/gast.1997.v113.pm9247457.

    PMID: 9247457BACKGROUND

  • Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009 Nov;41(4):1149-60. doi: 10.3758/BRM.41.4.1149.

    PMID: 19897823BACKGROUND

  • Kraichely RE, Arora AS, Murray JA. Opiate-induced oesophageal dysmotility. Aliment Pharmacol Ther. 2010 Mar;31(5):601-6. doi: 10.1111/j.1365-2036.2009.04212.x. Epub 2009 Dec 8.

    PMID: 20003176BACKGROUND

  • Conklin JL. Evaluation of Esophageal Motor Function With High-resolution Manometry. J Neurogastroenterol Motil. 2013 Jul;19(3):281-94. doi: 10.5056/jnm.2013.19.3.281. Epub 2013 Jul 8.

    PMID: 23875094BACKGROUND

MeSH Terms

Conditions

Esophageal Diseases

Interventions

naloxegol

Condition Hierarchy (Ancestors)

Gastrointestinal DiseasesDigestive System Diseases

Study Officials

  • Ron Schey, MD

    Temple University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 14, 2016

First Posted

December 20, 2016

Study Start

January 1, 2017

Primary Completion

October 1, 2018

Study Completion

October 1, 2018

Last Updated

December 24, 2018

Record last verified: 2018-12

Data Sharing

IPD Sharing
Will not share

Locations

US(1)