GCC Agonist Signal in the Small Intestine

Inclusion Criteria:

• Scheduled for clinically indicated esophagogastroduodenoscopy (EGD)

• Age >= 18 years of age. Note: Because no dosing or adverse event (AE) data arecurrently available on the use of plecanatide or linaclotide in participants < 18years of age, children and adolescents are excluded from this study but will beeligible for future pediatric trials, if applicable

• Willing to provide mandatory biospecimens as specified in the protocol

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Not pregnant or breastfeeding, as determined by pregnancy test prior to EGDprocedure. Note: The effects of plecanatide and linaclotide on the developing humanfetus at the recommended therapeutic dose are unknown. For this reason, women ofchild-bearing potential and men must agree to use adequate contraception (hormonalor barrier method of birth control; abstinence) prior to study entry and for 2 weeksafter discontinuing study agent. Should a woman become pregnant or suspect she ispregnant while participating in this study, she should inform her study physicianimmediately. Breastfeeding should be discontinued if the mother is treated withplecanatide or linaclotide

• Ability to understand and the willingness to sign a written informed consentdocument

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load

• Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) areeligible

Exclusion Criteria:

• Prior treatment in the past week with plecanatide, linaclotide, or other agent whoseprimary mechanism of action is that of a GCC agonist

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition of plecanatide or linaclotide

• Use of any other investigational agents =< 12 weeks prior to registration

• Uncontrolled intercurrent illness, or psychiatric illness/social situations thatwould limit compliance with study requirements

• History of gastric bypass, gastric sleeve, or bariatric surgery