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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Opioid Induced Constipation

Intervention / Treatment
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* Drug: Polyethylene Glycol 3350
* Drug: Movantik


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Crossover Group 1<br>Crossover Group Movantik to Polyethylene Glycol 3350 2-period, 2-treatment cross-over model: Subjects will be randomized to Movantik during Treatment period 1 (2 weeks), then crossed over to receive Polyethylene Glycol 3350 for Treatment period 2 (2 weeks) after 1 week washout. | Drug: Polyethylene Glycol 3350<br>* 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.<br>* Other names: MiraLAX;Drug: Movantik<br>* 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.<br>* Other names: Naloxegol;|
| Active Comparator: Crossover Group 2<br>Crossover group Polyethylene Glycol 3350 to Movantik 2-period, 2-treatment cross-over model: Subjects will be randomized to Polyethylene Glycol 3350 during Treatment period 1 (2 weeks), then crossed over to receive Movantik for Treatment period 2 (2 weeks) after 1 week washout. | Drug: Polyethylene Glycol 3350<br>* 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.<br>* Other names: MiraLAX;Drug: Movantik<br>* 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.<br>* Other names: Naloxegol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 
| 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). | 
| 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. | 
| 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. | 
| 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid Induced constipation,, constipation,, laxative,, bowel movement,, Movantik,, Naloxegol