| Eligibility |
Inclusion Criteria:
1. Subject is willing and able to participate in the study for the required duration,
understand and provide signed informed consent, and agrees to undergo all protocol
activities.
2. Subject is proficient in reading, writing, and speaking English.
3. Subject is able to complete all required electronic Daily Bowel Movement and Symptoms
Questionnaire, daily medication reconciliation surveys (Screening, Product Phase, and
Product/Placebo Phase), bi-weekly PAC-SYM and PAC QOL questionnaire, and monthly Study
Participant Global Assessment questionnaire entries during the 2 week Screening Phase
assessment period and for the duration of the study (ie, the 8 week randomized
Product/Placebo Phase, 4 week open label Product Phase and the 2 week Follow up
Phase).
4. Males or females between 18 and 75 years of age (inclusive), with a BMI = 19 and < 35
kg/m2. Females must not be pregnant or lactating.
5. Female Subjects of non childbearing potential whether surgically sterile or
postmenopausal.
6. Females who are still menstruating must be able to differentiate the abdominal
symptoms associated with CIC from those associated with their menses (otherwise
protocol assessments of these symptoms may be confounded).
7. Male and female Subjects of childbearing potential must agree to use adequate
contraception from the time of informed consent to 2 weeks after receiving the last
dose of study product.
8. Subject meets the Rome IV functional constipation criteria as modified for this study
for = 3 months prior to the Screening Call. The Rome IV criteria as modified for this
study, requires the following:
1. Subject reports that loose stool is rarely present without the use of laxatives.
2. Subject does not meet the Rome IV criteria for IBS C.
3. Subject does not use manual maneuvers (eg, digital evacuation, support of the
pelvic floor) to facilitate defecations.
4. Subject reports a history of < 3 complete spontaneous bowel movements per week.
5. Subject reports = 2 of the following:
i. Straining during = 25% of defecations ii. Lumpy or hard stool in = 25% of
defecations iii. Sensation of incomplete evacuation for = 25% of defecations iv.
Sensation of anorectal obstruction/blockage for = 25% of defecations
9. Subjects who meet the modified Rome IV criteria based on history must also demonstrate
the following during the 2 week Screening Phase diary assessment period:
a. < 3 CSBMs each week b. = 4 SBMs each week c. BSFS of 6 or 7 in < 25% of SBMs d. One
out of the following three: i. BSFS of 1 or 2 in = 25% of defecations ii. A straining
value recorded on = 25% of days when a BM was reported iii. = 25% of BMs result in a
sense of incomplete evacuation
Exclusion Criteria:
1. Subject has not maintained a stable diet for = 30 days prior to the Screening Call or
is unwilling to maintain a stable diet during the study.
2. Subject has had a surgical procedure requiring general anesthesia < 60 days before the
Screening Call.
3. Subject has had a colonoscopy in the past 30 days or is scheduled for colonoscopy
within the next 4 months and is unable/unwilling to postpone until the completion of
study participation.
4. Subject has a history of cancer (other than basal cell carcinoma of the skin) unless
the malignancy has been in a complete remission without maintenance therapy (eg,
chemotherapy, radiation, surgery) for = 5 years prior to the Screening Call.
5. Subject has any acute or chronic concomitant illness that could confound outcome
assessments for this study, including, but not limited to:
1. Known history of ulcerative colitis, Crohn's disease, colon cancer, current
stomach ulcers, pancreatitis, diverticulitis.
2. Known history of acute or chronic HBV, HCV, or HIV infection.
3. Known or suspected alcoholism, drug addiction, or significant drug abuse within 1
year of the Screening Call.
6. Subject has any known medical condition, clinical signs and symptoms, vital signs,
abnormal laboratory, or other testing, considered clinically significant by the
Investigator, that could interfere with the subject's participation in and completion
of the study including, but not limited to:
1. Uncontrolled hypertension.
2. Diabetes uncontrolled by diet (ie, requiring oral medication or insulin).
3. Previous anaphylactic reaction to any medication.
4. History of adrenal disease, diabetic nephropathy, or gastroparesis.
5. Uncontrolled hypothyroidism.
6. Untreated mental disorder
7. Spinal cord injury
7. Subject has a history of severe drug allergy or hypersensitivity, or known
hypersensitivity to any of the study product excipients.
8. Subject has had a cerebrovascular event (stroke) or myocardial infarction (MI) in the
last 6 months.
9. Subject has plans to travel outside the USA during the study period.
10. Subject has a disease or condition other than CIC that has been associated with or can
cause constipation.
11. Subject has a structural abnormality of the GI tract, or disease or condition that can
affect GI motility, or defecation.
12. History or presence of pseudo obstruction, colon cancer, malignant polyps, colitis,
ischemic colitis, abdominal adhesions, intestinal ischemia, esophageal atresia,
laxative or enema abuse, or pelvic floor dysfunction.
13. Subject has a current COVID 19 infection, or a history or a prior COVID 19 infection
with ongoing symptoms suggestive of "Long COVID".
14. Subject has active peptic ulcer disease not adequately treated or not stable with
therapy.
15. Subject is taking a pharmacologic treatment for gastroesophageal reflux disease
(GERD)/reflux that has not been stable for 15 days before the Screening Call.
16. Subject has a history of substantiated (documented by computed tomography (CT) scan or
hospitalization) diverticulitis, or any ongoing chronic condition (eg, chronic
pancreatitis, polycystic kidney disease, endometriosis, ovarian cysts, or other) that
may be associated with chronic abdominal pain or discomfort and might confound the
assessments in this study during the 2 years prior to the Screening Call.
17. Subject has had a fecal impaction that required hospitalization or emergency room
treatment < 3 months before the Screening Call.
18. Subject has a history of an eating disorder in the last 5 years.
19. Subject has had surgery that meets any of the following criteria:
1. Gastric bypass surgery or invasive procedure for the treatment of obesity or
surgery to remove a segment of the GI tract at any time prior to the Screening
Call
2. Subjects who have had a gastric band unless the band has been completely removed
> 60 days before the Screening Call
3. Open surgery of the abdomen, pelvis, or retroperitoneal structures within 6
months prior to the Screening Call
20. Laparoscopic appendectomy or cholecystectomy or other instrumentation of the bowel <
60 days before the Screening Call.
21. Subject meets the Rome IV criteria for IBS C. This includes subjects who report
abdominal pain or discomfort for = 1 day/week in the last 3 months, with symptom onset
= 6 months prior to diagnosis, and whose abdominal pain or discomfort is associated
with = 2 of the following symptoms:
1. Related to defecation
2. Associated with a change in frequency of stool
3. Associated with a change in form (consistency) of stool
22. Subject has had a barium enema within 7 days of the Screening Call.
23. Subject reports a clinically significant finding on colonoscopy.
24. Subject has taken a protocol prohibited drug within 15 days of the Screening Call or
is not willing to abide by the protocol restrictions regarding use of prohibited
drugs. (ie, medications that are known to either relieve or to potentially exacerbate
constipation).
25. Subject has taken antibiotics or narcotics within 60 days of the Screening Call
26. Subject has previously taken the study product at any time.
27. Subject reports the use of bisacodyl or other medication for constipation on > 2 days
in either of the 2 weeks in the Screening Phase assessment period.
28. Subject will be ineligible for randomization if, during the 2 week Screening Phase
assessment, he or she has failed to complete at least 6 of the 7 required daily 'Daily
Bowel Movement and Symptoms Questionnaire' questionnaires in each of the 2 weeks.
29. Subject uses bisacodyl or other medication for constipation within 72 hours before the
first dose of study product (PP Day 1), to avoid confounding the data collected in the
first week of study product administration, particularly the time to first BM.
30. Subject uses any narcotic during the course of the study.
Concomitant Treatment and Study Restrictions:
Prohibited concomitant treatments and study restrictions during the study and during the
indicated periods include:
1. Any investigational drug product, device, or biologic within 3 months or five half
lives (whichever is longer) prior to the Screening Call.
2. Any prescription or nonprescription medication for CIC.
3. Any prescription medication that has a significant risk of producing constipation.
(eg, prokinetics, metformin, systemic glucocorticosteroids, non steroidal anti
inflammatory drugs, ketoconazole, anticholinergics, or misoprostol) throughout any
phase of the study.
4. Use of enemas, suppositories, or stimulant laxatives to have a BM more than 2 days in
any week during the Screening, Product/Placebo and Product Phases.
5. Use of manual manipulation to have a BM.
6. Use of colon prep or high colonic throughout any phase of the study.
Permitted concomitant treatments and study restrictions during the study and during the
indicated periods include:
1. Regular intake of acetylsalicylic acid (ie, aspirin) at doses up to 162 mg/day is
permitted.
2. Rescue medication will not be provided; however, subjects may use bisacodyl
(preferred) or other medication for constipation when at least 72 hours have passed
since their previous BM or when their symptoms become intolerable. Use must be
documented with all other concomitant medication use.
Other medication considered necessary for the subject's safety and well being may be
allowed at the discretion of the investigator.
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