Dose-Finding Trial of Polyethylene Glycol 3350 Laxative Plus Electrolytes for the Treatment of Constipation (Protocol P07515)

Study Overview
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Brief Summary
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The primary objective of the study was to evaluate the proportion of subjects with a bowel movement (BM) without straining or without hard and/or lumpy stool within the first 24 h of treatment for subjects taking 1 of 3 single doses of Polyethylene Glycol (PEG) plus Electrolytes (PEG+E) (13.125 g, 26.25 g, 39.375 g). The doses specified relate to the doses of PEG. Secondary objectives were measured by analysis of a subject diary and self-reported BM data. The secondary objectives included comparisons of PEG+E doses at 24 h for: BM control; relief of gas; relief of bloating; and relief of abdominal discomfort/cramping. In addition, the proportion of subjects with a BM (without straining and without hard and/or lumpy stool) within the first 24 h of treatment for subjects taking different doses of PEG+E was evaluated for the time to first BM.

Official Title
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A Randomized, Open-Label, Dose-Finding Trial of Polyethylene Glycol 3350 Laxative Plus Electrolytes for the Treatment of Constipation

Conditions
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Constipation

Intervention / Treatment
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* Drug: PEG 3350 laxative plus electrolytes (PEG + E)/Macrogol (Movicol®, BAY81-8430)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A willingness to participate in the study and comply with its procedures Must be ambulatory Male or female subjects aged 18 years or older who met two or more of the following modified Rome III-based criteria for constipation: (a) straining during at least 25% of defecations; (b) lumpy or hard stools in at least 25% of defecations; (c) sensation of incomplete evacuation for at least 25% of defecation; (d) sensation of anorectal obstruction/blockage for at least 25% of defecations; (e) manual maneuvers to facilitate at least 25% of defecations (eg, digital evacuation, support of the pelvic floor), and (f) fewer than 3 defecations per week Criteria fulfilled for the last 3 months with symptom onset at least 6 mo prior to diagnosis Had a self reported or documented history of chronic constipation Agreed not to use laxatives other than the study treatment from baseline/informed consent to end-of-study Agreed to maintain a similar diet from the week before Visit 3 to the end-of-study were to be enrolled Additionally required not to use any treatment known to cause constipation during the study (for subjects enrolled after Amendment 1) If a female subject, either surgically sterile, 2 years postmenopausal, or using an acceptable method of contraception. Abstinence was not an acceptable method of contraception. Females of childbearing potential had to have a urine pregnancy test (human chorionic gonadotropin [HCG]) that was negative at Visit 3 Be able to read and write in the diaries in English Exclusion Criteria: Had loose stools without the use of laxatives Recurrent abdominal pain Known or suspected bowel perforation, obstruction, or fecal impaction; or had gastric retention, inflammatory bowel disease, bowel resection, or colostomy Celiac disease or known gluten sensitivity Known renal or hepatic insufficiency Recent history of alcohol abuse or drug abuse History of psychiatric disorders History of significant ongoing medical problems or scheduled for surgical procedures Subjects who, in the opinion of the Investigator, should not have been included in the study for any reason, including inability to follow study procedures Participated in an investigational clinical, surgical, drug or device study within the past 30 days Pregnant or lactating Allergic to PEG or PEG+E Employed by or have immediate family members employed by a company that manufactures laxative products Participant or family member of the Investigator or site staff directly involved with this study

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG + E, 13.125 g<br>Single sachet of PEG+E (13.125 g) dissolved in 125 mL of non-carbonated water ingested orally with entire volume taken at one time | Drug: PEG 3350 laxative plus electrolytes (PEG + E)/Macrogol (Movicol®, BAY81-8430)<br>* 13.125 g of PEG 3350 powder with approximately 0.6 g of electrolytes<br>|
| Experimental: PEG + E, 26.25 g<br>Two sachets of PEG+E (26.25 g) dissolved in 250 mL of non-carbonated water ingested orally with entire volume taken at one time | Drug: PEG 3350 laxative plus electrolytes (PEG + E)/Macrogol (Movicol®, BAY81-8430)<br>* 13.125 g of PEG 3350 powder with approximately 0.6 g of electrolytes<br>|
| Experimental: PEG + E, 39.375 g<br>Three sachets of PEG+E (39.375 g) dissolved in 375 mL of non-carbonated water ingested orally with entire volume taken at one time | Drug: PEG 3350 laxative plus electrolytes (PEG + E)/Macrogol (Movicol®, BAY81-8430)<br>* 13.125 g of PEG 3350 powder with approximately 0.6 g of electrolytes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Successful Bowel Movement (BM) Within 24 Hours of PEG + E Administration | A successful BM was defined as a BM with no straining or hard/lumpy stools. | From time of study drug treatment up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Time To First Successful BM In 0 Days Through 0.5 Days, >0.5 Days Through 1.0 Days, or >1.0 Days Through 1.5 Days After PEG+E Administration | Time to first successful bowel movement was defined as the duration (in days) from the time of first study dose of study treatment until first successful BM (defined as BM without straining and without hard and/or lumpy stool). | From time of study drug administration up to 3 Days | 
| Percentage of Participants With Successful BM Within 12 Hours of PEG+E Administration | A successful BM was defined as a BM with no straining or hard/lumpy stools. | From time of study drug treatment up to 12 hours | 
| Mean Visual Analog Scale (VAS) Rating for BM Control | The VAS is a psychometric response scale which measures responses along a continuum of values. The BM control VAS uses a 100 mm horizontal line with the two ends representing the opposite, extreme limits of the participant's experience of BM control. Participants marked where they felt they resided between the two ends with a vertical line. The distance from the left end of the VAS (0 mm) to the participant's mark was measured and recorded in mm. BM Control ratings ranged on a continuous scale from 0 to 100 mm, where 0 mm=Calm, not urgent and 100 mm= Not able to hold BM, very urgent. Participants completed a VAS after every BM or attempted BM. The VAS ratings recorded in the diaries for each BM were averaged (with range) to yield a single score for each participant. Participant scores were then averaged by treatment group | From time of study drug treatment up to 24 hours | 
| Mean VAS Rating for Gas | The VAS is a psychometric response scale which measures responses along a continuum of values. The Gas VAS uses a 100 mm horizontal line with the two ends representing opposite, extreme limits of the participant's experience with BM-related gas. Participants marked where they felt they resided between the two ends with a vertical line. The distance from the left end of the VAS (0 mm) to the participant's mark was measured and recorded in mm. Gas ratings ranged on a continuous scale from 0 to 100 mm, where 0 mm=None and 100 mm= Severe. Participants completed a VAS after every BM or attempted BM. The VAS ratings recorded in the diaries for each BM were averaged (with range) to yield a single score for each participant. Participant scores were then averaged by treatment group. | From time of study drug treatment up to 24 hours | 
| Mean VAS Rating for Bloating | The VAS is a psychometric response scale which measures responses along a continuum of values. The Bloating VAS uses a 100 mm horizontal line with the two ends representing opposite, extreme limits of the participant's experience with BM-related bloating. Participants marked where they felt they resided between the two ends with a vertical line. The distance from the left end of the VAS (0 mm) to the participant's mark was measured and recorded in mm. Bloating ratings ranged on a continuous scale from 0 to 100 mm, where 0 mm=None and 100 mm= Severe. Participants completed a VAS after every BM or attempted BM. The VAS ratings recorded in the diaries for each BM were averaged (with range) to yield a single score for each participant. Participant scores were then averaged by treatment group. | From time of study drug treatment up to 24 hours | 
| Mean VAS Rating for Abdominal Discomfort/Cramping | The VAS is a psychometric response scale which measures responses along a continuum of values. The Abdominal Discomfort/Cramping VAS uses a 100 mm horizontal line with the two ends representing opposite, extreme limits of the participant's experience with BM-related abdominal discomfort/cramping. Participants marked where they felt they resided between the two ends with a vertical line. The distance from the left end of the VAS (0 mm) to the participant's mark was measured and recorded in mm. Abdominal discomfort/cramping ratings ranged on a continuous scale from 0 to 100 mm, where 0 mm=None and 100 mm= Painful. Participants completed a VAS after every BM or attempted BM. The VAS ratings recorded in the diaries for each BM were averaged (with range) to yield a single score for each participant. Participant scores were then averaged by treatment group. | From time of study drug treatment up to 24 hours | 
| Mean Participant Global Assessment of Treatment | At the End of Study Visit, the study staff asked the participant to rate their global assessment of the study treatment according to the following categories: 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective. | From time of study drug administration up to 2 Days |