Naloxegol for Opioid-Related Gastroparesis

NCT03036891 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 24102
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastroparesis; Opioid Use

Keywords

Gastroparesis; Opioid-Induced; Delayed Gastric Emptying

Outcome Measures

Primary Outcomes (1)

• Gastric Emptying (GE t-1/2)

  Improvement in gastric emptying (GE t-1/2) compared to Placebo

  4 week

Secondary Outcomes (5)

• Daily Symptom Improvement using the GCSI-DD (Gastroparesis Cardinal Symptom Index-Daily Diary)

  4 weeks

• Symptom Improvement using PAGI-SYM

  4 weeks

• Pain Management using the McGill Pain Inventory

  4 weeks

• Overall improvement in Gastric Emptying (GE t-1/2)

  8 week

• Quality of Life based on SF-36

  4 weeks

Study Arms (2)

Study Group

EXPERIMENTAL

Naloxegol 25 mg, oral tablet, daily for 4 weeks

Drug: Naloxegol 25 MG Oral Tablet [Movantik]

Placebo Control

PLACEBO COMPARATOR

Placebo Oral Tablet, 25 mg, oral tablet, daily for 4 weeks

Drug: Placebo Oral Tablet

Interventions

Naloxegol 25 MG Oral Tablet [Movantik] DRUG

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.

Also known as: Study

Study Group

Placebo Oral Tablet DRUG

Patients will be given Placebo (Placebo 25 mg).They will take this daily in the morning 1 hour before breakfast for four weeks.

Also known as: Control

Placebo Control

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-84, Males or Females
• 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
• 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.
• Delayed gastric emptying based on previous scintigraphy (Percent gastric retention \>60% at 2 hours and/or \>10% retention at 4 hours
• Signing informed consent prior to any study specific procedures

You may not qualify if:

• Prior gastric resective surgery such as bariatric surgery, antrectomy.
• Presence of severe renal impairment (CrCl\<60 ml/min)
• Presence of severe hepatic impairment - Child-Pugh Classification Class C, generally AST\>200 or ALT\>200 or Total bilirubin \>3.0.
• Other conditions besides gastroparesis that could potentially slow gastric emptying, such as untreated hypothyroidism.
• Concomitants use of strong CYP 3A4 inhibitors (such as ketoconazole, diltiazem, erythromycin, clarithromycin), use of CYP3A4 inducer.
• Use of NSAIDs and/or Plavix/Clopidogrel
• Any prior use of Movantik (the study drug) or other opioid receptor antagonist (e.g., Relistor (methylnaltrexone), naltrexone, or naloxone) before the screening visit.
• Patients with known cancer or cancer history within last 5 years prior to the screening visit.
• Patients with GI obstruction and/or perforation or conditions with potential for GI perforation.
• Patients with disruption to the blood-brain barrier;
• Current use of a medication affecting gastric motility such as metoclopramide, domperidone, and erythromycin;
• Pregnant women, females planning to become pregnant, and nursing mothers.
• Women of childbearing potential who are unwilling to use contraceptives throughout the course of treatment
• Subjects with severe co-morbidities (Cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, neurologic) based on PI's clinical judgment.
• Active substance abuse.

Sponsors & Collaborators

• Temple University: lead
• AstraZeneca: collaborator

Study Sites (1)

Lewis Katz School of Medicine at Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Related Publications (18)

• Parkman HP, Hasler WL, Fisher RS; American Gastroenterological Association. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004 Nov;127(5):1592-622. doi: 10.1053/j.gastro.2004.09.055.

  PMID: 15521026 BACKGROUND

• Abell TL, Bernstein RK, Cutts T, Farrugia G, Forster J, Hasler WL, McCallum RW, Olden KW, Parkman HP, Parrish CR, Pasricha PJ, Prather CM, Soffer EE, Twillman R, Vinik AI. Treatment of gastroparesis: a multidisciplinary clinical review. Neurogastroenterol Motil. 2006 Apr;18(4):263-83. doi: 10.1111/j.1365-2982.2006.00760.x.

  PMID: 16553582 BACKGROUND

• Parkman HP, Yates K, Hasler WL, Nguyen L, Pasricha PJ, Snape WJ, Farrugia G, Koch KL, Calles J, Abell TL, McCallum RW, Lee L, Unalp-Arida A, Tonascia J, Hamilton F; National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium. Similarities and differences between diabetic and idiopathic gastroparesis. Clin Gastroenterol Hepatol. 2011 Dec;9(12):1056-64; quiz e133-4. doi: 10.1016/j.cgh.2011.08.013. Epub 2011 Aug 24.

  PMID: 21871247 BACKGROUND

• Anantharamu T, Sharma S, Gupta AK, Dahiya N, Singh Brashier DB, Sharma AK. Naloxegol: First oral peripherally acting mu opioid receptor antagonists for opioid-induced constipation. J Pharmacol Pharmacother. 2015 Jul-Sep;6(3):188-92. doi: 10.4103/0976-500X.162015.

  PMID: 26312011 BACKGROUND

• Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014 Jun 19;370(25):2387-96. doi: 10.1056/NEJMoa1310246. Epub 2014 Jun 4.

  PMID: 24896818 BACKGROUND

• Revicki DA, Rentz AM, Dubois D, Kahrilas P, Stanghellini V, Talley NJ, Tack J. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther. 2003 Jul 1;18(1):141-50. doi: 10.1046/j.1365-2036.2003.01612.x.

  PMID: 12848636 BACKGROUND

• Revicki DA, Rentz AM, Tack J, Stanghellini V, Talley NJ, Kahrilas P, De La Loge C, Trudeau E, Dubois D. Responsiveness and interpretation of a symptom severity index specific to upper gastrointestinal disorders. Clin Gastroenterol Hepatol. 2004 Sep;2(9):769-77. doi: 10.1016/s1542-3565(04)00348-9.

  PMID: 15354277 BACKGROUND

• Revicki DA, Camilleri M, Kuo B, Norton NJ, Murray L, Palsgrove A, Parkman HP. Development and content validity of a gastroparesis cardinal symptom index daily diary. Aliment Pharmacol Ther. 2009 Sep 15;30(6):670-80. doi: 10.1111/j.1365-2036.2009.04078.x. Epub 2009 Jun 25.

  PMID: 19558608 BACKGROUND

• Abell TL, Camilleri M, Donohoe K, Hasler WL, Lin HC, Maurer AH, McCallum RW, Nowak T, Nusynowitz ML, Parkman HP, Shreve P, Szarka LA, Snape WJ Jr, Ziessman HA; American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. J Nucl Med Technol. 2008 Mar;36(1):44-54. doi: 10.2967/jnmt.107.048116. Epub 2008 Feb 20.

  PMID: 18287197 BACKGROUND

• Maranki JL, Lytes V, Meilahn JE, Harbison S, Friedenberg FK, Fisher RS, Parkman HP. Predictive factors for clinical improvement with Enterra gastric electric stimulation treatment for refractory gastroparesis. Dig Dis Sci. 2008 Aug;53(8):2072-8. doi: 10.1007/s10620-007-0124-7. Epub 2007 Dec 14.

  PMID: 18080765 BACKGROUND

• Szarka LA, Camilleri M, Vella A, Burton D, Baxter K, Simonson J, Zinsmeister AR. A stable isotope breath test with a standard meal for abnormal gastric emptying of solids in the clinic and in research. Clin Gastroenterol Hepatol. 2008 Jun;6(6):635-643.e1. doi: 10.1016/j.cgh.2008.01.009. Epub 2008 Apr 14.

  PMID: 18406670 BACKGROUND

• Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975 Sep;1(3):277-299. doi: 10.1016/0304-3959(75)90044-5.

  PMID: 1235985 BACKGROUND

• Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-197. doi: 10.1016/0304-3959(87)91074-8.

  PMID: 3670870 BACKGROUND

• Culpepper-Morgan JA, Inturrisi CE, Portenoy RK, Foley K, Houde RW, Marsh F, Kreek MJ. Treatment of opioid-induced constipation with oral naloxone: a pilot study. Clin Pharmacol Ther. 1992 Jul;52(1):90-5. doi: 10.1038/clpt.1992.106.

  PMID: 1623695 BACKGROUND

• Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007.

  PMID: 12924748 BACKGROUND

• Peachey JE, Lei H. Assessment of opioid dependence with naloxone. Br J Addict. 1988 Feb;83(2):193-201. doi: 10.1111/j.1360-0443.1988.tb03981.x. No abstract available.

  PMID: 3345396 BACKGROUND

• Tompkins DA, Bigelow GE, Harrison JA, Johnson RE, Fudala PJ, Strain EC. Concurrent validation of the Clinical Opiate Withdrawal Scale (COWS) and single-item indices against the Clinical Institute Narcotic Assessment (CINA) opioid withdrawal instrument. Drug Alcohol Depend. 2009 Nov 1;105(1-2):154-9. doi: 10.1016/j.drugalcdep.2009.07.001. Epub 2009 Aug 3.

  PMID: 19647958 BACKGROUND

• Gandek B, Sinclair SJ, Kosinski M, Ware JE Jr. Psychometric evaluation of the SF-36 health survey in Medicare managed care. Health Care Financ Rev. 2004 Summer;25(4):5-25.

  PMID: 15493441 BACKGROUND

MeSH Terms

Conditions

Gastroparesis

Interventions

naloxegol; Tablets

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Henry Parkman, MD

  Temple University Hospita

  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

Model Details: 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

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: January 30, 2017
• Study Start: December 29, 2016
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: August 27, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)