Browse EPPT > MAY2017-09-01
Phase I Double-Blind, Placebo-Controlled Trial of 27 mg Dolcanatide (SP-333) to Demonstrate Colorectal Bioactivity in Healthy Volunteers
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
