To Evaluate Patient Preference of Movantik and Polyethylene Glycol 3350 for Opioid Induced Constipation

Opioid Induced Constipation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03060512
• Other study ID #: D3820L00017
• Status: Completed
• Phase: Phase 4
• Start date: March 2, 2017
• Est. completion date: August 23, 2017

Study information

• Verified date: July 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: August 23, 2017
• Est. primary completion date: August 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

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

Related Conditions & MeSH terms

• Constipation
• Opioid Induced Constipation

Intervention

Drug:
• Polyethylene Glycol 3350
Polyethylene Glycol 3350, 17 grams of powder to be dissolved in 4 to 8 ounces of water, juice, soda, coffee or tea to be taken once a day. Bisacodyl 5mg, 1-3 tablets may be taken by subject who does not experience a bowel movement within 72 hours.
• Movantik
Movantik 25 mg, 1 tablet taken once a day on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal. Bisacodyl 5mg, 1-3 tablets may be taken by subject who does not experience a bowel movement within 72 hours.

Locations

Country	Name	City	State
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Anaheim	California
United States	Research Site	Anaheim	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Beavercreek	Ohio
United States	Research Site	Biloxi	Mississippi
United States	Research Site	Bloomington	Illinois
United States	Research Site	Brownsburg	Indiana
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Collegeville	Pennsylvania
United States	Research Site	Decatur	Georgia
United States	Research Site	DeLand	Florida
United States	Research Site	Edmond	Oklahoma
United States	Research Site	Endwell	New York
United States	Research Site	Fort Myers	Florida
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greer	South Carolina
United States	Research Site	High Point	North Carolina
United States	Research Site	Huntsville	Alabama
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jupiter	Florida
United States	Research Site	Kingsport	Tennessee
United States	Research Site	Lake City	Florida
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Levittown	Pennsylvania
United States	Research Site	Lincoln	California
United States	Research Site	Los Gatos	California
United States	Research Site	Marietta	Georgia
United States	Research Site	Miami	Florida
United States	Research Site	Miami Springs	Florida
United States	Research Site	North Hollywood	California
United States	Research Site	North Miami Beach	Florida
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orange	California
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pikesville	Maryland
United States	Research Site	Plantation	Florida
United States	Research Site	Port Orange	Florida
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Diego	California
United States	Research Site	Trenton	New Jersey
United States	Research Site	Troy	Michigan
United States	Research Site	Waltham	Massachusetts
United States	Research Site	West Jordan	Utah
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Westminster	California
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Wyoming	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	QuintilesIMS, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (11)

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/pm — View 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.1526-463 — View 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: — View 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. — View 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 — View 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 — View Citation

Holzer P. New approaches to the treatment of opioid-induced constipation. Eur Rev Med Pharmacol Sci. 2008 Aug;12 Suppl 1:119-27. Review. — View 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. — View Citation

Johanson JF. Review of the treatment options for chronic constipation. MedGenMed. 2007 May 2;9(2):25. Review. — View 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. Review. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient Reported Preference for Movantik or PEG 3350 for Opioid-induced Constipation (OIC) Treatment	The Patient Preference Assessment was conducted at Visit 5 using a 7-point scale in subjects with chronic non-cancer pain. The 3 categories were formed by collapsing the 7-point rating scale to: 1. Prefer Movantik (including Strong preference for Movantik, Moderate preference for Movantik, Slight preference for Movantik), 2. No preference, and 3. Prefer PEG 3350 (including Strong preference for PEG 3350, Moderate preference for PEG 3350, and Slight preference for PEG 3350). The number of subjects in each category is presented for the total number of subjects in the Per-Protocol (PP) Set.	From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
Primary	Patient Reported Preference for Movantik or PEG 3350 for OIC Treatment by Treatment Sequence	The Patient Preference Assessment was conducted at Visit 5 using a 7-point scale in subjects with chronic non-cancer pain. The following categories were the possible responses: Strong preference for Movantik, Moderate preference for Movantik, Slight preference for Movantik, No preference, Slight preference for PEG 3350, Moderate preference for PEG 3350 and Strong preference for PEG 3350. Prefer Movantik included subjects in the categories Strong preference for Movantik, Moderate preference for Movantik and Slight preference for Movantik. Prefer PEG 3350 included subjects in the categories Strong preference for PEG 3350, Moderate preference for PEG 3350 and Slight preference for PEG 3350. Preference for Period 1 treatment and Preference for Period 2 treatment included subjects who preferred the first and second treatments respectively taken within a given treatment sequence. The number of subjects in each category is presented per treatment sequence for subjects in the PP Set.	From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
Secondary	Patient Reported Influence of Each Medication Characteristic Median Scores That Contributed to Their Overall Preference for Movantik or PEG 3350	In order to assess the reason for patient preference of Movantik or PEG 3350, subjects reported on the influence of 5 medication characteristics using a 4-point rating scale. The following were the scale options: efficacy ('worked better to relieve my OIC'), tolerability ('tolerated better'), convenience ('was more convenient'), works quickly ('worked quickly') and works predictably ('worked predictably'). For each characteristic, influence scores were rated as: 0 = No influence, 1 = Mildly influenced, 2 = Moderately influenced or 3 = Strongly influenced. The scale range for each characteristic was from 0 to 3, and the median score for each characteristic is presented for the overall PP Set according to which treatment was preferred.; The assessment was only completed by subjects who indicated an overall preference.	From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
Secondary	Patient Reported Influence of Each Medication Characteristic Individual Category Results That Contributed to Their Overall Preference for Movantik or PEG 3350	In order to assess the reason for patient preference of Movantik or PEG 3350, subjects reported on the influence of 5 medication characteristics using a 4-point rating scale. The following were the scale options: efficacy ('worked better to relieve my OIC'), tolerability ('tolerated better'), convenience ('was more convenient'), works quickly ('worked quickly') and works predictably ('worked predictably'). For each characteristic, influence scores were rated as: 0 = No influence, 1 = Mildly influenced, 2 = Moderately influenced or 3 = Strongly influenced. The scale range for each characteristic was from 0 to 3, and the number of subjects in each characteristic category is presented for the overall PP Set according to which treatment was preferred.; The assessment was only completed by subjects who indicated an overall preference.	From Visit 2 (Day 1) of Treatment Period 1 to Visit 5 (Day 36) of Treatment Period 2 (end of study).
Secondary	Patient Global Impression of Change (PGIC) Questionnaire to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms	PGIC was measured on a 7-point scale at the end of each two-week treatment period to assess the subject's impression of the effectiveness of the treatment received for OIC. The scoring was as follows: 1 = No change (or condition has gotten worse); 2 = Almost the same, hardly any change at all; 3 = A little better, but no noticeable change; 4 = Somewhat better, but the change has not made any real difference; 5 = Moderately better, and a slight but noticeable change; 6 = Better and a definite improvement that has made a real and worthwhile difference; and 7 = A great deal better and a considerable improvement that has made all the difference. The score range is from 1 to 7, with 1 indicating the least improvement and 7 indicating the greatest improvement in OIC symptoms.; Mean score results are presented for each treatment for Visits 3 and 5.	At Visit 3 (Day 15) of Treatment Period 1 and Visit 5 (Day 36) of Treatment Period 2.
Secondary	PGIC Questionnaire Individual Item Results to Compare the Impact of Movantik and PEG 3350 on OIC Symptoms	PGIC was measured on a 7-point scale at the end of each two-week treatment period to assess the subject's impression of the effectiveness of the treatment received for OIC. The subjects selected one of the following PGIC items as their response: 1 = No change (or condition has gotten worse); 2 = Almost the same, hardly any change at all; 3 = A little better, but no noticeable change; 4 = Somewhat better, but the change has not made any real differences; 5 = Moderately better, and a slight but noticeable change; 6 = Better and a definite improvement that has made a real and worthwhile difference; and 7 = A great deal better and a considerable improvement that has made all the difference. The score range is from 1 to 7, with 1 indicating the least improvement and 7 indicating the greatest improvement in OIC symptoms.; The number of subjects responding to each PGIC item at Visits 3 and/or 5 is presented for each treatment overall.	At Visit 3 (Day 15) of Treatment Period 1 and Visit 5 (Day 36) of Treatment Period 2.
Secondary	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	The BFI is a 3-item questionnaire administered by a study clinician to measure constipation from the subject's perspective (ease of defecation, feeling of complete evacuation, and personal judgment of constipation). For each item the subject was asked to rate their response on a scale from 0 to 100, where 0 indicates the best response (easy/no diffculty) and 100 the worst response (severe difficulty). The total BFI score was calculated as the mean of the 3 item scores.; The mean change from baseline in BFI scores at Visits 3 and/or 5 are presented.	From Baseline (Visit 2, Day 1) to Visit 3 (Day 15) and Visit 5 (Day 36).

External Links

•   Movantik_D3820L00017_Protocol_Original-26Jan17_Redacted_PDF-A
•   Movantik_D3820L00017_SAP_Redacted_15Aug2017_PDF-A