The Effect of CSP01 on Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03054506
• Collaborator: Gelesis, Inc. (Industry)
• Enrollment: 52
• Location: 1
• Arms: 3
• Actual Duration (Months): 22.9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

Constipation is a common gastrointestinal motility disorder that is often chronic, negatively affects patients' daily lives. Constipation occurs when bowel movements become difficult or less frequent.This study is being done to study the effectiveness of the hydrogel capsule, CSP01, compared to the active control (carboxymethylcellulose) and placebo (non-medicine sugar pill), to relieve constipation among subjects with chronic idiopathic constipation (CIC) or with irritable bowel syndrome with constipation (IBS-C).

Condition or Disease	Intervention/Treatment	Phase
Constipation; Chronic Idiopathic Constipation; Irritable Bowel Syndrome With Constipation	Device: CSP01; Device: Carboxymethylcellulose (CMC); Device: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Single Center, Double-blind, Parallel-group, Placebo-controlled Study Assessing the Effect of CSP01 on Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation
• Actual Study Start Date: Mar 7, 2017
• Actual Primary Completion Date: May 10, 2018
• Actual Study Completion Date: Feb 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CSP01 Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief.	Device: CSP01; Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Active Comparator: Carboxymethylcellulose (CMC) Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day.	Device: Carboxymethylcellulose (CMC); Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Placebo Comparator: Placebo Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day.	Device: Placebo; Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Colonic Transit Time (CTT) [Up to 1 week; measured once during the run-in-period and again during third week of the treatment period]

   Colonic Transit Time is the amount of time (in minutes) that the SmartPill capsule spent in the large intestine before expulsion. We measured the difference between CTT pre-treatment and post-treatment and calculated the mean difference for each treatment group. Negative values equal a reduction in CTT.

Secondary Outcome Measures

1. Complete Spontaneous Bowel Movement (CSBM) Frequency Rate [55 days (baseline, treatment, & follow-up)]

   Average number of Complete Spontaneous Bowel Movements per day (BMs where participant felt that they emptied their bowels). More CSBMs are interpreted as a better outcome.

2. Stool Consistency [55 days (baseline, treatment, & follow-up)]

   Stool consistency for each bowel movement based on the Bristol Stool Scale A descriptive numerical scale from 1 to 7 where lower numbers indicate constipation, numbers toward the middle indicate normal stool consistence, and the highest numbers indicate diarrhea. Therefore middle scores mean a better outcome 1= hard lumps 2 = lumpy sausage 3 = cracked sausage 4 = smooth sausage 5 = soft lumps 6 = mushy 7 = watery

3. Ease of Passage Rating [55 days (baseline, treatment, & follow-up)]

   Patient assessment of the ease with which bowel movements are passed using a descriptive numerical scale where lower numbers indicate difficult passage of stool, numbers toward the middle indicate more normal passage of stool, and numbers on the highest end indicate abnormally urgent passage of stool. Middle scores indicate a better outcome. = manual disimpaction needed = enema needed = straining needed = normal = urgent without pain = urgent with pain = incontinent

4. Patient's Assessment of Abdominal Discomfort [55 days (baseline, treatment, & follow-up)]

   Patient's daily assessment of abdominal discomfort using a numerical rating scale of 0 to 10, where 0 = no discomfort at all and 10 = severe discomfort. Higher scores mean a worse outcome.

5. Patient Assessment of Bloating Severity [55 days (baseline, treatment, & follow-up)]

   Patient's daily assessment of bloating severity using a numerical rating scale from 0 to 10 where 0 = no bloating at all and 10 = severe bloating. Higher scores mean a worse outcome.

6. Patient Assessment of Constipation Severity [55 days (baseline, treatment, & follow-up)]

   Patient's daily assessment of constipation severity using a numerical rating scale from 0 to 10 where 0 = no constipation at all and 10 = severe constipation. Higher numbers mean a worse outcome.

7. Relief Rating [55 days (baseline, treatment, & follow-up)]

   Patient's feeling of overall relief after each bowel movement using a numerical rating scale from 0 to 10 where 0 = no relief and 10 = complete relief. Higher scores mean a better outcome (feeling more relief after a bowel movement).

8. Patient Assessment of Constipation - Symptoms (PAC-SYM) [Day -14 to Day 22]

   Patient assessment of constipation symptom severity questionnaire. A validated 12-question questionnaire. Numerical scale from 0 to 4 where 0 = absent and 4 = very severe. Possible total score ranges from 0 to 48. Higher total PAC-SYM scores mean a worse outcome. PAC-SYM was completed at four time-points (Day -14, Day 0, Day 15, & Day 22). Scores were aggregated based on time period as either pre- (Day -14 & Day 0) or post- (Day 15 & Day 22) treatment start. Values reported are averages based on patient total scores from these time points. Data was specifically analyzed based on patient diagnosis in addition to treatment.

9. Patient Assessment of Constipation - Quality of Life (PAC-QOL) [Day -14 to Day 22]

   Patient Assessment of Constipation Quality of Life Questionnaire. A validated questionnaire containing 28 total questions with four sub-sections each broadly ranging from "not at all" to "all of the time" on 0 to 4 scales. Possible total range is 0 to 112. An overall higher total score on the PAC-QOL means a worse outcome. PAC-QOL was completed at four time-points (Day -14, Day 0, Day 15, & Day 22). Scores were aggregated based on time period as either pre- (Day -14 & Day 0) or post- (Day 15 & Day 22) treatment start. Values reported are averages based on patient total scores from these time points. Data was specifically analyzed based on patient diagnosis in addition to treatment.

10. Need for Rescue Laxatives [55 days (baseline, treatment, & follow-up)]

    Number of total days that rescue laxatives were used by participants in each treatment group. (The number of days that rescue laxatives were used by each individual patient was calculated and added to the treatment group total)

11. Spontaneous Bowel Movement (SBM) Frequency [55 days (baseline, treatment, & follow-up)]

    Average number of Spontaneous Bowel Movements per day. (Spontaneous Bowel Movements include both complete and incomplete bowel movements)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 22-70 years old

2. BMI >18.5 and <35 kg/m2

3. Rome III criteria for functional constipation or IBS-C

4. Continued IBS-C or CIC throughout Run-in period

5. Compliant with reporting during Run-in (confirm the presence of constipation during the 7-day Run-in baseline period; patients are required to report an average of <3 continuous spontaneous bowel movements [CSBMs] and ≤6 spontaneous bowel movements [SBMs] per week via the interactive web response system).

6. Ability to follow verbal and written instructions

7. Ability to record daily bowel habits, including frequency, stool consistency (BSFS), straining (EoPS), completeness of evacuation, and Patient Reported Outcomes (PROs) (abdominal discomfort, severity of constipation, bloating, overall relief)

8. Informed consent form signed by the subjects

Exclusion Criteria:

1. History of loose stools

2. History of irritable bowel syndrome with diarrhea (IBS-D) or mixed irritable bowel syndrome (IBS-M)

3. Non-compliance with reporting during Run-in

4. Patients reporting laxative, enema, and/or suppository usage for >2 days or any usage of a prohibited medication during the Run-in period

5. Patients reporting watery stools for any SBM (Type 7 on the Bristol Stool Form Scale [BSFS]) or loose (mushy) stools for >1 SBM (Type 6 on the BSFS) in the absence of laxatives during Run-in

6. GI motility obstruction or GI tract structural abnormality

7. Current use of prescribed or illicit opioids

8. History of pelvic floor dysfunction

9. Need for manual maneuvers in order to achieve a BM

10. History of GI lumen surgery at any time or other GI or abdominal operations within 60 days prior to entry into the study

11. History of high-dose stimulative or cathartic laxative abuse as judged by investigator team

12. Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study

13. Cardiovascular disease, diabetes, cancer, Crohn's disease, ulcerative colitis

14. BMI of <18.5 or >35 kg/m2

15. Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential) or lactation

16. Absence of contraception in females of childbearing potential

17. History of allergic reaction to carboxymethylcellulose, citric acid, sodium stearyl fumarate, raw cane sugar, gelatin, or titanium dioxide

18. Administration of investigational products within 1 month prior to Screening Visit

19. Exclusion of colonic inertia with symptoms of < 1 BM per 2 weeks

20. Subjects anticipating surgical intervention during the study

21. Known history of diabetes (type 1 or 2)

22. History of eating disorders including binge eating (except mild binge eater)

23. Supine SBP > 160 mm Hg and/or supine DBP > 95 mm Hg (mean of two consecutive readings)

24. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit

25. History of swallowing disorders

26. Esophageal anatomic abnormalities (e.g., webs, diverticuli, rings)

27. History of gastric bypass or any other gastric surgery

28. History of small bowel resection (except if related to appendectomy)

29. History of gastric or duodenal ulcer

30. History of gastroparesis

31. History of abdominal radiation treatment

32. History of pancreatitis

33. History of intestinal stricture (e.g., Crohn's disease)

34. History of intestinal obstruction or subjects at high risk of intestinal obstruction including suspected small bowel adhesions

35. History of malabsorption

36. History of sucrose intolerance

37. History of hepatitis B or C

38. History of human immunodeficiency virus

39. History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)

40. Any other clinically significant disease interfering with the assessments of Gelesis100, according to the Investigator (e.g., disease requiring corrective treatment, potentially leading to study discontinuation)

41. HbA1c > 8.5% (> 69 mmol/mol)

42. Positive test for drugs in the urine

43. Any relevant biochemical abnormality interfering with the assessments of Gelesis100, according to the Investigator

44. Antidiabetic medications within 1 month prior to Screening Visit (except stable dose of metformin, ≤ 1500 mg/day, for at least 1 month in subjects with type 2 diabetes)

45. Medications requiring mandatory administration with meal at lunch or dinner

46. Anticipated requirement for use of prohibited concomitant medications

47. Implanted or externally worn medical device such as, but not limited to, a pacemaker, infusion pump, or insulin pump

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Gelesis, Inc.

Investigators

• Principal Investigator: Kyle Staller, MD, MPH, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 30, 2017
• Informed Consent Form - Oct 25, 2017

More Information

Publications

None provided.

• Responsible Party: Kyle Staller, MD, MPH, Kyle Staller, MD, MPH, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03054506
• Other Study ID Numbers: 2016P001751
• First Posted: Feb 15, 2017
• Last Update Posted: Aug 20, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation; Carboxymethylcellulose Sodium

Study Results

Participant Flow

Pre-assignment Detail	52 patients signed the consent form and thus were considered enrolled. 4 failed screening 48 passed screening 5 withdrew before run-in 1 lost to follow-up 42 started run-in 2 failed run-in 40 randomized 1 withdrew due to AE 39 completed study 1 patient's follow-up CTT data irretrievable (technical malfunction) 38 complete CTTs

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Period Title: Overall Study
STARTED	20	11	9
COMPLETED	19	11	9
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo	Total
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Total of all reporting groups
Overall Participants	20	11	9	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 75%	9 81.8%	8 88.9%	32 80%
>=65 years	5 25%	2 18.2%	1 11.1%	8 20%
Sex: Female, Male (Count of Participants)
Female	19 95%	9 81.8%	7 77.8%	35 87.5%
Male	1 5%	2 18.2%	2 22.2%	5 12.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 18.2%	0 0%	2 5%
Not Hispanic or Latino	20 100%	9 81.8%	9 100%	38 95%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 5%	1 9.1%	1 11.1%	3 7.5%
Native Hawaiian or Other Pacific Islander	1 5%	0 0%	0 0%	1 2.5%
Black or African American	2 10%	1 9.1%	0 0%	3 7.5%
White	16 80%	8 72.7%	8 88.9%	32 80%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 9.1%	0 0%	1 2.5%
Region of Enrollment (participants) [Number]
United States	20 100%	11 100%	9 100%	40 100%
Diagnosis: CIC, IBS-C (Count of Participants)
Chronic Idiopathic Constipation	14 70%	9 81.8%	4 44.4%	27 67.5%
Irritable Bowel Syndrome with Constipation	6 30%	2 18.2%	5 55.6%	13 32.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Colonic Transit Time (CTT)
Description	Colonic Transit Time is the amount of time (in minutes) that the SmartPill capsule spent in the large intestine before expulsion. We measured the difference between CTT pre-treatment and post-treatment and calculated the mean difference for each treatment group. Negative values equal a reduction in CTT.
Time Frame	Up to 1 week; measured once during the run-in-period and again during third week of the treatment period

Outcome Measure Data

Analysis Population Description

All participants who completed the study. (39 participants) Note: One participant who received placebo had pre-treatment CTT data, but post-treatment CTT data was irretrievable due to technical malfunction. This subject's pre-treatment CTT data is included in analysis, but no post-treatment CTT data.

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Mean (Standard Deviation) [minutes]	-727 (1277)	-15 (2226)	366 (1714)

2. Secondary Outcome

Title	Complete Spontaneous Bowel Movement (CSBM) Frequency Rate
Description	Average number of Complete Spontaneous Bowel Movements per day (BMs where participant felt that they emptied their bowels). More CSBMs are interpreted as a better outcome.
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment CSBM measurement

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	0.2 (0.2)	0.2 (0.2)	0.2 (0.3)
Post-treatment	0.3 (0.3)	0.3 (0.2)	0.3 (0.3)

3. Secondary Outcome

Title	Stool Consistency
Description	Stool consistency for each bowel movement based on the Bristol Stool Scale A descriptive numerical scale from 1 to 7 where lower numbers indicate constipation, numbers toward the middle indicate normal stool consistence, and the highest numbers indicate diarrhea. Therefore middle scores mean a better outcome 1= hard lumps 2 = lumpy sausage 3 = cracked sausage 4 = smooth sausage 5 = soft lumps 6 = mushy 7 = watery
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment stool consistency ratings.

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	3.62 (0.56)	3.54 (0.45)	3.88 (0.65)
Post-treatment	3.81 (0.44)	3.62 (0.59)	3.59 (0.63)

4. Secondary Outcome

Title	Ease of Passage Rating
Description	Patient assessment of the ease with which bowel movements are passed using a descriptive numerical scale where lower numbers indicate difficult passage of stool, numbers toward the middle indicate more normal passage of stool, and numbers on the highest end indicate abnormally urgent passage of stool. Middle scores indicate a better outcome. = manual disimpaction needed = enema needed = straining needed = normal = urgent without pain = urgent with pain = incontinent
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment ease of passage ratings

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	3.62 (0.56)	3.54 (0.45)	3.88 (0.65)
Post-treatment	3.81 (0.44)	3.62 (0.59)	3.59 (0.63)

5. Secondary Outcome

Title	Patient's Assessment of Abdominal Discomfort
Description	Patient's daily assessment of abdominal discomfort using a numerical rating scale of 0 to 10, where 0 = no discomfort at all and 10 = severe discomfort. Higher scores mean a worse outcome.
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment abdominal discomfort ratings

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	3.91 (1.75)	3.55 (1.43)	3.82 (2.23)
Post-treatment	3.67 (1.91)	3.08 (1.41)	3.58 (2.60)

6. Secondary Outcome

Title	Patient Assessment of Bloating Severity
Description	Patient's daily assessment of bloating severity using a numerical rating scale from 0 to 10 where 0 = no bloating at all and 10 = severe bloating. Higher scores mean a worse outcome.
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment bloating ratings.

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	4.36 (2.20)	4.43 (1.42)	4.67 (2.47)
Post-treatment	4.17 (2.22)	3.89 (1.16)	3.98 (2.80)

7. Secondary Outcome

Title	Patient Assessment of Constipation Severity
Description	Patient's daily assessment of constipation severity using a numerical rating scale from 0 to 10 where 0 = no constipation at all and 10 = severe constipation. Higher numbers mean a worse outcome.
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment constipation severity ratings

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	4.11 (2.06)	4.04 (1.34)	4.15 (2.53)
Post-treatment	3.46 (1.77)	3.29 (1.15)	3.85 (2.50)

8. Secondary Outcome

Title	Relief Rating
Description	Patient's feeling of overall relief after each bowel movement using a numerical rating scale from 0 to 10 where 0 = no relief and 10 = complete relief. Higher scores mean a better outcome (feeling more relief after a bowel movement).
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment relief ratings

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	4.27 (1.95)	4.21 (1.91)	4.11 (1.78)
Post-treatment	5.11 (2.29)	4.86 (1.99)	4.38 (1.79)

9. Secondary Outcome

Title	Patient Assessment of Constipation - Symptoms (PAC-SYM)
Description	Patient assessment of constipation symptom severity questionnaire. A validated 12-question questionnaire. Numerical scale from 0 to 4 where 0 = absent and 4 = very severe. Possible total score ranges from 0 to 48. Higher total PAC-SYM scores mean a worse outcome. PAC-SYM was completed at four time-points (Day -14, Day 0, Day 15, & Day 22). Scores were aggregated based on time period as either pre- (Day -14 & Day 0) or post- (Day 15 & Day 22) treatment start. Values reported are averages based on patient total scores from these time points. Data was specifically analyzed based on patient diagnosis in addition to treatment.
Time Frame	Day -14 to Day 22

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment PAC-SYM ratings

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment (CIC Group)	17.62 (6.98)	17.56 (4.90)	12.75 (6.85)
Post-treatment (CIC Group)	11.77 (7.43)	9.22 (4.09)	10.25 (3.86)
Pre-treatment (IBS Group)	18.67 (11.08)	17.00 (4.24)	17.40 (7.30)
Post-treatment (IBS Group)	13.17 (7.41)	16.00 (4.24)	15.20 (10.18)

10. Secondary Outcome

Title	Patient Assessment of Constipation - Quality of Life (PAC-QOL)
Description	Patient Assessment of Constipation Quality of Life Questionnaire. A validated questionnaire containing 28 total questions with four sub-sections each broadly ranging from "not at all" to "all of the time" on 0 to 4 scales. Possible total range is 0 to 112. An overall higher total score on the PAC-QOL means a worse outcome. PAC-QOL was completed at four time-points (Day -14, Day 0, Day 15, & Day 22). Scores were aggregated based on time period as either pre- (Day -14 & Day 0) or post- (Day 15 & Day 22) treatment start. Values reported are averages based on patient total scores from these time points. Data was specifically analyzed based on patient diagnosis in addition to treatment.
Time Frame	Day -14 to Day 22

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment PAC-QOL ratings

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment (CIC Group)	39.08 (17.09)	31.22 (6.57)	26.50 (14.25)
Post-treatment (CIC Group)	26.46 (18.30)	20.56 (4.42)	19.75 (6.99)
Pre-treatment (IBS Group)	41.00 (17.01)	32.00 (4.24)	34.30 (14.48)
Post-treatment (IBS Group)	30.33 (20.20)	23.00 (1.41)	35.60 (8.53)

11. Secondary Outcome

Title	Need for Rescue Laxatives
Description	Number of total days that rescue laxatives were used by participants in each treatment group. (The number of days that rescue laxatives were used by each individual patient was calculated and added to the treatment group total)
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had daily medication usage data

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Number [days]	13	6	3

12. Secondary Outcome

Title	Spontaneous Bowel Movement (SBM) Frequency
Description	Average number of Spontaneous Bowel Movements per day. (Spontaneous Bowel Movements include both complete and incomplete bowel movements)
Time Frame	55 days (baseline, treatment, & follow-up)

Outcome Measure Data

Analysis Population Description

All participants who completed the study and had both pre and post treatment SBM measurements

Arm/Group Title	CSP01	Carboxymethylcellulose (CMC)	Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.	Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
Measure Participants	19	11	9
Pre-treatment	0.75 (0.29)	0.70 (0.40)	0.75 (0.39)
Post-treatment	0.95 (0.36)	0.79 (0.35)	0.89 (0.58)

Adverse Events

Time Frame	Adverse event data was collected for each subject throughout the study duration, from study enrollment to final day in study (includes 9-day follow-up period). Study duration was approximately 46-59 days.
Adverse Event Reporting Description	All participants of the study were assessed for adverse events throughout the duration of the study. Adverse events were recorded, logged, and reported to the IRB where applicable. In-person follow-up was arranged for participants experiencing an adverse event to monitor resolution of symptoms.
Arm/Group Title	CSP01		Carboxymethylcellulose (CMC)		Placebo
Arm/Group Description	Subjects in the experimental group will receive CSP01, a non-systemic, orally administered hydrogel capsule, twice a day. CSP01 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine. By acting as a bulking agent and possibly reducing colonic transit time through increase of colonic water content, CSP01 may contribute to constipation relief. CSP01: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.		Subjects in the active control group will receive orally administered 3 capsules of carboxymethylcellulose (CMC) capsules twice a day. Carboxymethylcellulose (CMC): Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.		Matching placebo consists of an inert mixture supplied by Gelesis Inc. in identical-appearing capsules.Subjects in the placebo group will be administered 3 capsules of placebo twice a day. Placebo: Subjects will take three capsules in the morning before breakfast, and three capsules at night before dinner each day for three weeks.
All Cause Mortality
	CSP01		Carboxymethylcellulose (CMC)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/11 (0%)		0/9 (0%)
Serious Adverse Events
	CSP01		Carboxymethylcellulose (CMC)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/11 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	CSP01		Carboxymethylcellulose (CMC)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/11 (0%)		0/9 (0%)
Gastrointestinal disorders
Constipation and back pain caused by constipation	1/20 (5%)	1	0/11 (0%)	0	0/9 (0%)	0

Limitations/Caveats

Target number of participants needed to achieve target power was not attained. One subject's post-treatment SmartPill data was irretrievable due to unexpected technical malfunction, therefore post-treatment colonic transit time was not collected.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.