Intervention: Plecanatide
Trial phase: Phase 1
ATC code: A06AX07
SMILES: CC(C)CC(NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(CCC(=O)O)NC(=O)C(NC(=O)C(CCC(=O)O)NC(=O)C(CC(=O)O)NC(=O)C(N)CC(N)=O)CSSCC(NC(=O)C(C)NC(=O)C(C(C)C)NC(=O)C(CC(N)=O)NC(=O)C(C(C)C)NC2=O)C(=O)NC(C(C)O)C(=O)NCC(=O)N1)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 14
Group description: Participants receive dolcanatide PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.
Eligibility criteria:
Inclusion Criteria:

PRE-REGISTRATION INCLUSION
Able to understand and willingness to sign a written informed consent document and follow study procedures
Willing to abstain from grapefruit juice during study
Willing to employ adequate contraception for men and women of childbearing potential; Note: acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status documented by serum follicle stimulating hormone (FSH), and/or documentation of surgical sterilization
Willing to provide blood and tissue specimens for research purposes
REGISTRATION INCLUSION
Normal organ function and have normal laboratory findings without clinically significant findings
Leukocytes >= 3 x 10^3/microliter (B/L)
Absolute neutrophil count >= 1.5 x 10^3/microliter (B/L)
Platelets >= 100 x 10^3/microliter (B/L)
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal (ULN)
Creatinine =< institutional upper limit of normal
Body mass index < 35 kg/m^2
No findings in the rectum of advanced adenoma, chronic inflammation, or cancer

Exclusion Criteria:

PRE-REGISTRATION EXCLUSION
Documented history of advanced adenomas (>= 1 cm in maximal diameter, >= 3 in total number, villous morphology, or high-grade dysplasia) or colorectal cancer
Family history of polyposis syndrome (e.g., familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) or colorectal cancer (first degree relatives younger than 60 years old)
History of gastroparesis
History of surgery involving the luminal gastrointestinal (GI) tract, including bariatric surgery; exception: prior appendectomy >= 60 days prior to pre-registration is not an exclusion criterion
History of celiac disease
Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
Previous diagnosis of irritable bowel syndrome, chronic constipation, functional bowel disorders, colonic motility disorder, or opioid-induced constipation
Any malignancy within 3 years of baseline; exception: participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator
Currently receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to dolcanatide or to any of the excipients
History of difficulty with sigmoidoscopy or abnormal colorectal anatomy
Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or lactating women
Current use of laxatives more than 3 times per week
Current use of >= 5 cigarettes/day
Current use of >= 3 alcoholic drinks/day
Use of anti-coagulants or anti-platelet agents within 5 days prior to anticipated sigmoidoscopy; exception: individuals taking aspirin will not be excluded and will not be subject to a wash-out period
History of bleeding/coagulation problems
Any medical condition reported by the participant or documented in the medical record that is judged by the investigator to constitute a risk to safe participation
Known or suspected mechanical gastrointestinal obstruction
REGISTRATION EXCLUSION
Sigmoidoscopy finding requiring clinical intervention
Use of any illicit or illegal substances detected by urinary drug screen