Constipation
Conditions
Brief summary
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.
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.
Interventions
DRUGPolyethylene 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.
DRUGPlacebo
Oral 17 g dose of Placebo solution concentrate in a volume of approximately 30 mL, once a day, for 14 days.
DRUGBisacodyl 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.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Inflammation of the Oral Mucosa | Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment | 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). |
| Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment | 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). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PEG 3350 Participants received 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, were provided for use as a rescue medication if a participant had not had a bowel movement for 72 hours after start of treatment. | 31 |
| Placebo Participants received a 17 g dose of Placebo solution concentrate solution 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, were provided for use as a rescue medication if a participant had not had a bowel movement for 72 hours after start of treatment. | 34 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal of Consent | 1 | 0 |
Baseline characteristics
| Characteristic | PEG 3350 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.5 Years STANDARD_DEVIATION 13.87 | 48.0 Years STANDARD_DEVIATION 15.17 | 46.4 Years STANDARD_DEVIATION 14.56 |
| Sex: Female, Male Female | 24 Participants | 27 Participants | 51 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 31 | 17 / 34 |
| serious Total, serious adverse events | 0 / 31 | 0 / 34 |
Outcome results
Primary
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).
Time frame: Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment
Population: Safety Population, which consisted of all participants who received at least 1 dose of PEG 3350 or placebo and had at least 1 postdose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 0=No inflammation | 31 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 1=Mild inflammation | 0 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 2=Moderate inflammation | 0 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 3=Severe inflammation | 0 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: Not evaluated | 0 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 0=No inflammation | 26 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 1=Mild inflammation | 2 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 2=Moderate inflammation | 1 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 3=Severe inflammation | 0 Participants |
| PEG 3350 | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: Not evaluated | 2 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 2=Moderate inflammation | 3 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 0=No inflammation | 34 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 0=No inflammation | 29 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 1=Mild inflammation | 0 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: Not evaluated | 1 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 2=Moderate inflammation | 0 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 1=Mild inflammation | 1 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: 3=Severe inflammation | 0 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 3: 3=Severe inflammation | 0 Participants |
| Placebo | Number of Participants With Inflammation of the Esophageal Mucosa | Visit 2: Not evaluated | 0 Participants |
Primary
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).
Time frame: Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment
Population: Safety Population, which consisted of all participants who received at least 1 dose of PEG 3350 or placebo and had at least 1 postdose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: Not evaluated | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 0=No inflammation | 31 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 1=Mild inflammation | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 2=Moderate inflammation | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 3=Severe inflammation | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 0=No inflammation | 29 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 1=Mild inflammation | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 2=Moderate inflammation | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 3=Severe inflammation | 0 Particpants |
| PEG 3350 | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: Not evaluated | 2 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 2=Moderate inflammation | 0 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 0=No inflammation | 33 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 0=No inflammation | 34 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: Not evaluated | 1 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 1=Mild inflammation | 0 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 1=Mild inflammation | 0 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 2=Moderate inflammation | 0 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 3: 3=Severe inflammation | 0 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: 3=Severe inflammation | 0 Particpants |
| Placebo | Number of Participants With Inflammation of the Oral Mucosa | Visit 2: Not evaluated | 0 Particpants |