Clinical trial NCT03060512: To Evaluate Patient Preference of Movantik and Polyethylene Glycol 3350 for Opioid Induced Constipation
Official title: A Phase IV, Randomized, Multi-Center, Open-Label, Prospective, Crossover Study to Evaluate Patient Preference of Movantik™ Versus Polyethylene Glycol 3350 for Opioid-Induced Constipation (OIC) Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Opioid Induced Constipation
Keywords: Opioid Induced constipation,
constipation,
laxative,
bowel movement,
Movantik,
Naloxegol
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: QuintilesIMS, Inc.
First posted: 2017-02-23
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether patients with opioid induced constipation prefer treatment with naloxegol (Movantik) or with Polyethylene Glycol 3350.

Detailed description: This study is a prospective, randomized, open-label crossover study consisting of a 1-week washout period, a 2-week treatment period, another 1-week washout and a final 2-week treatment period. The study will assess the overall patient preference Movantik versus Polyethylene Glycol 3350 for the treatment of their opioid-induced constipation. This study will also evaluate the reasons for patient preference (only among subjects who indicate a preference), patient global impression of change, and change in bowel function over the treatment periods measured by Bowel Function Index. Patient's bowel movement diary will also be collected during the study.

Eligibility criteria: Inclusion Criteria:

* Male or female between the ages of ≥18 and \<85 years
* Self-reported active symptoms of OIC (Opioid Induced Constipation) based on components of the Rome IV criteria at screening. Patients should have at least 2 of the following:

  * \<3 SBMs (Spontaneous Bowel Movements) per week
  * Straining \>25% of defecations
  * Sensation of incomplete evacuation \>25% of defecations
  * Lumpy or hard stools \>25% of defecations
  * Sensation of anorectal obstruction/blockage \>25% of defecations
* Confirmed OIC by BFI (Bowel Function Index) ≥30
* Stable maintenance opioid regimen consisting of a total daily dose of at least 30 mg of oral morphine, or equivalent of 1 or more other opioid therapies
* Willingness to stop all laxatives and other bowel regimens other than specified rescue medication

Exclusion Criteria:

* Pain related to cancer or has a history of cancer within 5 years
* Current constipation or chronic constipation not caused by or related to use of opioids
* History of rectal evacuation disorders, surgery or procedures that can potentially affect pelvic floor function; requirement of using manual maneuvers to facilitate a bowel movement
* Evidence of significant GI structural abnormalities, acute or chronic GI conditions that could post risk to the patient or confound the study results
* Recent surgery that may affect GI motility or increase risk for bowel obstruction or perforation
* Severe hepatic impairment
* Moderate or severe renal impairment
* Condition that may affect the permeability of blood-brain barrier
* Concomitantly using strong or moderate CYP3A4 inhibitors and strong CYP3A4 inducers
* Any other significant and/or progressive medical, surgical, psychiatric, or mental health condition or any significant laboratory findings that could increase the risk of participation in the study or affect the interpretation of study data as determined by the Investigator

Primary outcomes:
measure: Patient Reported Preference for Movantik or PEG 3350 for Opioid-induced Constipation (OIC) Treatment
timeFrame: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
measure: Patient Reported Preference for Movantik or PEG 3350 for OIC Treatment by Treatment Sequence
timeFrame: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
Secondary outcomes:
measure: Patient Reported Influence of Each Medication Characteristic Median Scores That Contributed to Their Overall Preference for Movantik or PEG 3350
timeFrame: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
measure: Patient Reported Influence of Each Medication Characteristic Individual Category Results That Contributed to Their Overall Preference for Movantik or PEG 3350
timeFrame: From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
measure: Patient Global Impression of Change (PGIC) Questionnaire to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms
timeFrame: At Visit 3 (Day 15) of Treatment Period 1 and Visit 5 (Day 36) of Treatment Period 2.
measure: PGIC Questionnaire Individual Item Results to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms
timeFrame: At Visit 3 (Day 15) of Treatment Period 1 and Visit 5 (Day 36) of Treatment Period 2.
measure: Mean Change From Baseline at Visit 3/5 in Bowel Function Index (BFI) Questionnaire Scores to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms
timeFrame: From Baseline (Visit 2, Day 1) to Visit 3 (Day 15) and Visit 5 (Day 36).
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Anaheim
country: United States
facility: Research Site
state: California
city: Lincoln
country: United States
facility: Research Site
state: California
city: Los Gatos
country: United States
facility: Research Site
state: California
city: North Hollywood
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Westminster
country: United States
facility: Research Site
state: California
city: DeLand
country: United States
facility: Research Site
state: Florida
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Jupiter
country: United States
facility: Research Site
state: Florida
city: Lake City
country: United States
facility: Research Site
state: Florida
city: Miami Springs
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: North Miami Beach
country: United States
facility: Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Research Site
state: Florida
city: Plantation
country: United States
facility: Research Site
state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Decatur
country: United States
facility: Research Site
state: Georgia
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Bloomington
country: United States
facility: Research Site
state: Illinois
city: Brownsburg
country: United States
facility: Research Site
state: Indiana
city: Pikesville
country: United States
facility: Research Site
state: Maryland
city: Waltham
country: United States
facility: Research Site
state: Massachusetts
city: Troy
country: United States
facility: Research Site
state: Michigan
city: Wyoming
country: United States
facility: Research Site
state: Michigan
city: Biloxi
country: United States
facility: Research Site
state: Mississippi
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Trenton
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Endwell
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: High Point
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Beavercreek
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Collegeville
country: United States
facility: Research Site
state: Pennsylvania
city: Levittown
country: United States
facility: Research Site
state: Pennsylvania
city: Greer
country: United States
facility: Research Site
state: South Carolina
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Kingsport
country: United States
facility: Research Site
state: Tennessee
city: West Jordan
country: United States
facility: Research Site
state: Utah
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Scientific Leadership
role: STUDY_DIRECTOR
References:
citation: Argoff CE, Brennan MJ, Camilleri M, Davies A, Fudin J, Galluzzi KE, Gudin J, Lembo A, Stanos SP, Webster LR. Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation. Pain Med. 2015 Dec;16(12):2324-37. doi: 10.1111/pme.12937. Epub 2015 Nov 19.
citation: Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 2009 Jan;10(1):35-42. doi: 10.1111/j.1526-4637.2008.00495.x. Epub 2008 Aug 18.
citation: Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil. 2014 Oct;26(10):1386-95. doi: 10.1111/nmo.12417. Epub 2014 Aug 28.
citation: 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.
citation: Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014 May 23;6:269-81. doi: 10.2147/CEOR.S61602. eCollection 2014.
citation: Coyne KS, Margolis MK, Yeomans K, King FR, Chavoshi S, Payne KA, LoCasale RJ. Opioid-Induced Constipation Among Patients with Chronic Noncancer Pain in the United States, Canada, Germany, and the United Kingdom: Laxative Use, Response, and Symptom Burden Over Time. Pain Med. 2015 Aug;16(8):1551-65. doi: 10.1111/pme.12724. Epub 2015 Mar 20.
citation: Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective outcome measures. J Manipulative Physiol Ther. 2004 Jan;27(1):26-35. doi: 10.1016/j.jmpt.2003.11.003.
citation: Holzer P. New approaches to the treatment of opioid-induced constipation. Eur Rev Med Pharmacol Sci. 2008 Aug;12 Suppl 1(0 1):119-27.
citation: Johanson JF. Review of the treatment options for chronic constipation. MedGenMed. 2007 May 2;9(2):25.
citation: Kumar L, Barker C, Emmanuel A. Opioid-induced constipation: pathophysiology, clinical consequences, and management. Gastroenterol Res Pract. 2014;2014:141737. doi: 10.1155/2014/141737. Epub 2014 May 5.
citation: McGraw T. Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial. Clin Exp Gastroenterol. 2016 Jul 15;9:173-80. doi: 10.2147/CEG.S111693. eCollection 2016.
citation: Brenner DM, Hu Y, Datto C, Creanga D, Camilleri M. A Randomized, Multicenter, Prospective, Crossover, Open-Label Study of Factors Associated With Patient Preferences for Naloxegol or PEG 3350 for Opioid-Induced Constipation. Am J Gastroenterol. 2019 Jun;114(6):954-963. doi: 10.14309/ajg.0000000000000229.