Safety and Tolerability of Oral Polyethylene Glycol (PEG 3350) Solution in Participants With Constipation (MK-8114-003)

Evaluation of Oral Tolerance MiraLAX Solution Concentrate in Subjects With Chronic Constipation

The purpose of this study is to compare the safety and tolerability of oral ingestion of PEG 3350 solution concentrate to oral ingestion of a placebo solution concentrate, in participants with constipation.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: Polyethylene Glycol (PEG 3350); Drug: Bisacodyl laxative tablets (rescue medication); Drug: Placebo

Detailed Description

This was a randomized, single-blind, placebo-controlled study to evaluate the proportion of participants with abnormalities of the oral mucosa detected by visual examination of the oral cavity in the polyethylene glycol (PEG) 3350 group compared with the placebo group. The study was also to evaluate the proportion of participants with abnormalities of the esophageal mucosa detected by endoscopic examination of the esophagus in the PEG 3350 group compared with the placebo group, and to compare the safety and tolerability by evaluation of the proportion of participants with the occurrence of adverse events (AEs) or adverse drug reactions.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ambulatory male or female with no history or current evidence of other conditions or abnormalities that would affect study results or interfere with participation for full duration of study
• meets diagnostic criteria for functional constipation. This includes loose stools that are rarely present without the use of laxatives and 2 or more of the following: straining during at least 25% of defecations; lumpy or hard stools in at least 25% of defecations; sensation of incomplete evacuation for at least 25% of defecations; sensation of anorectal obstruction/blockage for at least 25% of defecations; manual maneuvers to facilitate at least 25% of defecations [e.g., digital evacuation, support of the pelvic floor]; and fewer than 3 defecations per week. Criteria for functional constipation must be fulfilled for last 3 months, with symptom onset at least 6 months prior to diagnosis.
• continuous or recurrent symptoms for at least 3 months of: abdominal pain or discomfort, relieved with defecation, or associated with a change in frequency or consistency of stool, and an irregular pattern of defecation at least 25% of the time with 3 or more of the following: altered stool frequency, altered stool form (hard or loose/watery), altered stool passage (straining or urgency, feeling of incomplete evacuation), passage of mucus, and bloating or abdominal distension
• agrees to not use laxatives other than study medication for the duration of the study period
• agrees to not use disallowed concomitant medications for the duration of the study
• agrees to maintain a similar diet and level of activity from the period of the Screening Visit through End of Study
• individuals of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control and until 2 weeks after the last dose of study drug in the last treatment period. Acceptable methods of birth control include: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, or vasectomy.

Exclusion Criteria:

• abnormal baseline endoscopy and/or an oral exam
• baseline oral exam showing evidence of oral lesions, such as herpes labialis or aphthous stomatitis, or known self-reported history or current periodontal gum disease
• history of impaired swallowing or difficulties swallowing foods and liquids
• known, history of, or suspected gastrointenstinal disease, including bowel perforation, obstruction, fecal impaction; irritable bowel syndrome (IBS), delayed gastric emptying, gastroparesis, gastroesophageal reflux disease (GERD), gastritis or peptic ulcer disease (PUD), dehydration, inflammatory bowel disease, bowel resection, anal fistulas/fissures, colostomy, etc.
• severe or unexplained abdominal pain
• history of or current alcohol or drug abuse
• history of malignancy ≤5 years prior to signing the informed consent, except for adequately treated basal cell and/or squamous cell skin cancer or in situ cervical cancer
• history of psychiatric illness requiring medications or hospitalization within the previous 12 months
• history of concurrent illness that required hospitalization within 4 weeks prior to Day -1 of the study
• allergies or allergic reactions or intolerance to any of the products used in study
• any degree of renal impairment
• major surgery or clinically significant illness within 4 weeks prior to Day -1 of Visit 1
• current or recent (within the past 30 days of signing informed consent) participation in a study with an investigational compound or device
• refusal to agree not to donate eggs or sperm upon the first study drug administration and thereafter through 90 days after the last study drug administration
• individual is an employee or family member of an employee of the sponsor or clinical unit where study will be conducted

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEG 3350; Participants will receive a 17 g dose of PEG 3350 solution concentrate in a volume of approximately 30 mL, once a day, for 14 days. Bisacodyl laxative tablets, 5.0 mg, 1 to 3 tablets in a single daily dose, will be provided for use as a rescue medication if a participant has not had a bowel movement for 72 hours after start of treatment.	Drug: Polyethylene Glycol (PEG 3350); Oral 17 g dose of PEG 3350 solution concentrate in a volume of approximately 30 mL, once a day, for 14 days.; Other Names: MiraLAX Solution Concentrate; Drug: Bisacodyl laxative tablets (rescue medication); 5.0 mg tablets, 1 to 3 tablets in a single daily dose, to be provided for use as rescue medication if participant has not had bowel movement for 72 hours after start of treatment.
Placebo Comparator: Placebo; Participants will receive a 17 g dose of Placebo solution concentrate in a volume of approximately 30 mL, once a day, for 14 days. Bisacodyl laxative tablets, 5.0 mg, 1 to 3 tablets in a single daily dose, will be provided for use as a rescue medication if a participant has not had a bowel movement for 72 hours after start of treatment.	Drug: Bisacodyl laxative tablets (rescue medication); 5.0 mg tablets, 1 to 3 tablets in a single daily dose, to be provided for use as rescue medication if participant has not had bowel movement for 72 hours after start of treatment.; Drug: Placebo; Oral 17 g dose of Placebo solution concentrate in a volume of approximately 30 mL, once a day, for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Inflammation of the Oral Mucosa	Participants underwent visual examination of the oral muscosa at Visit 2 and Visit 3. Measurements were based on 0-3 Likert Scale Scores: 0 = No inflammation (no erythema, no erosion/ulceration); 1 = Mild inflammation (erythema without erosion/ulceration); 2 = Moderate inflammation (erythema with erosion); 3 = Severe inflammation (erythema with ulceration).	Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment
Number of Participants With Inflammation of the Esophageal Mucosa	Participants underwent endoscopic examination of the esophageal mucosa at Visit 2 and Visit 3. Measurements were based on 0-3 Likert Scale Scores: 0 = No inflammation (no erythema, no erosion/ulceration); 1 = Mild inflammation (erythema without erosion/ulceration); 2 = Moderate inflammation (erythema with erosion); 3 = Severe inflammation (erythema with ulceration).	Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: June 19, 2013
• First Submitted That Met QC Criteria: June 19, 2013
• First Posted (Estimate): June 24, 2013

Study Record Updates

• Last Update Posted (Estimate): March 11, 2015
• Last Update Submitted That Met QC Criteria: February 20, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Gastrointestinal Agents; Cathartics; Bisacodyl; Polyethylene glycol 3350; Laxatives
• Other Study ID Numbers: 18127; CL2012-13 (Other Identifier: Consumer Health Protocol Number); 8114-003 (Other Identifier: Merck)