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

The following datasets contain the data available for EPPT MAY2017-09-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Files	Description
Data Dictionary (PDF - 924.5 KB)	1. The Enhanced Person dataset contains all information relevant for most analyses. Each record represents one person and contains updated variable names, formats, and labels. All information coming from non-person-based datasets has been converted into a person-based format.
Data Dictionary (PDF - 230.3 KB)	2. The Adverse Events dataset contains adverse event information, including onset date, grade of severity, attribution to the study agent, and outcome. This version of the dataset includes updated variable names, formats, and labels.

Raw Datasets

These 38 datasets contain the raw form data received, excluding PII.

Show these datasets

Files	Description
Data Dictionary (PDF - 229.0 KB)	1. The Alcohol Questionnaire dataset contains alcohol use questionnaire pertaining to time during trial.
Data Dictionary (PDF - 244.0 KB)	2. The Alcohol Questionnaire Baseline dataset contains baseline alcohol use questionnaire.
Data Dictionary (PDF - 224.8 KB)	3. The Baseline Events dataset contains participant finishing baseline eligibility information.
Data Dictionary (PDF - 230.9 KB)	4. The Blood Chemistry Lab dataset contains blood chemistry results.
Data Dictionary (PDF - 230.2 KB)	5. The Blood Hematoloty Lab dataset contains blood hematoligy results.
Data Dictionary (PDF - 212.8 KB)	6. The cGMP Averages dataset contains CGMP day mean results.
Data Dictionary (PDF - 218.6 KB)	7. The cGMP Results dataset contains CGMP raw results.
Data Dictionary (PDF - 239.3 KB)	8. The Concomitant Medications dataset contains concomitant medication names and usage.
Data Dictionary (PDF - 226.7 KB)	9. The Demographics dataset contains basic demographic information.
Data Dictionary (PDF - 227.3 KB)	10. The End Active Treatment dataset contains end active treatment details and reasons.
Data Dictionary (PDF - 234.6 KB)	11. The Endoscopy dataset contains endoscopy details and results.
Data Dictionary (PDF - 235.7 KB)	12. The Medical/Surgical History dataset contains participant submitted medical and surgical history.
Data Dictionary (PDF - 227.9 KB)	13. The Participant Enrollment dataset contains participant enrollment information.
Data Dictionary (PDF - 235.0 KB)	14. The Physical Exam dataset contains comprehensive physical exam and anthropometry.
Data Dictionary (PDF - 224.0 KB)	15. The Pregnancy Test dataset contains pregnancy test results.
Data Dictionary (PDF - 261.9 KB)	16. The Pre-Registration Checklist dataset contains pre-registration checklist with eligibility.
Data Dictionary (PDF - 240.9 KB)	17. The Pre-Registration Exclusion dataset contains pre-registration exclusions.
Data Dictionary (PDF - 227.6 KB)	18. The Pre-Registration Inclusion dataset contains pre-registration inclusions.
Data Dictionary (PDF - 259.9 KB)	19. The Primary Endpoints dataset contains primary endpoint results and data used for analysis.
Data Dictionary (PDF - 231.6 KB)	20. The Protocol Data dataset contains protocal intervention and drug dosing data.
Data Dictionary (PDF - 224.6 KB)	21. The Protocol Interruption dataset contains protocal intervention information.
Data Dictionary (PDF - 244.1 KB)	22. The Registration Checklist dataset contains registration checklist with eligibilitry.
Data Dictionary (PDF - 222.2 KB)	23. The Registration Exclusion dataset contains registration exclusions.
Data Dictionary (PDF - 222.3 KB)	24. The Registration Inclusion dataset contains registration inclusions.
Data Dictionary (PDF - 226.2 KB)	25. The Safety dataset contains adverse event and toxicity information.
Data Dictionary (PDF - 225.5 KB)	26. The Screen dataset contains screen eligibility results.
Data Dictionary (PDF - 226.1 KB)	27. The Specimen Tissue dataset contains tissue specimen details.
Data Dictionary (PDF - 228.7 KB)	28. The Step Information dataset contains protocol step information.
Data Dictionary (PDF - 224.4 KB)	29. The Supporting Documents dataset contains supporting documentation details.
Data Dictionary (PDF - 229.4 KB)	30. The Symptoms dataset contains participant symptoms at screening.
Data Dictionary (PDF - 253.8 KB)	31. The Tobacco Questionnaire dataset contains tobacco use form pertaining to time during trial.
Data Dictionary (PDF - 268.7 KB)	32. The Tobacco Questionnaire Baseeline dataset contains baseline tobacco use form.
Data Dictionary (PDF - 243.7 KB)	33. The Toxicity dataset contains adverse event and toxicity information.
Data Dictionary (PDF - 227.2 KB)	34. The Treatment Assignment dataset contains treatment assignment details and timing.
Data Dictionary (PDF - 227.3 KB)	35. The Treatment Events dataset contains participant progressing to the 21 day follow-up period information.
Data Dictionary (PDF - 213.4 KB)	36. The Unblinding dataset contains participant unblinding dataset.
Data Dictionary (PDF - 228.6 KB)	37. The Urine Lab dataset contains urinalysis results.
Data Dictionary (PDF - 233.5 KB)	38. The Was It Worth It Questionnaire dataset contains was it worth it questionnaire responses.

Trial Summary

This study was performed to determine the effect of Dolcanatide on colorectal bioactivity in healthy volunteers. 27 volunteers were randomized, 25 completed the study intervention, and 24 completed the study intervention and post-intervention procedures.

Dolcanatide was administered to the volunteers in a dose of 27mg daily for 7 days.

The study concluded that mean differences in cGMP levels, before and after treatment, were similar in both arms. Dolcanatide also did not produce a pharmacodynamics (PD) response in any volunteers in the intervention arm of the trial. Dolcanatide was well tolerated amongst all randomized subjects.

Randomized trial with two arms:

• Arms
  • Arm I: Dolcanatide 27 mg tablet daily for 7 days.
  • Arm II: Placebo tablet daily for 7 days.

Enrollment Statistics

Expected Enrollment: 40

Actual Enrollment: 37

• 27 participants randomized
  • 10 not randomized (ineligible, comorbidity or concomitant medications)
• 25 completed intervention (25 of 37)
• 24 completed post-intervention tests (24 of 37)

Total Study Population Demographics (27 Randomized and Eligible People):

• Age (years):
  • Mean: 47.2
  • Range: 45.8-57.9
  • Median: 50.4
• Height (cm):
  • Mean: 171
  • IQR: 164 - 180
  • Range: 158 - 183
  • Median: 172
• Weight (kg):
  • Mean: 84
  • IQR: 74 - 90
  • Range: 38 - 112
  • Median: 82
• Sex
  • Females: 4 (14.8%)
  • Males: 23 (85.2%)

Final Analysis Population: 24

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

Schema

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Here, we demonstrate that administration of oral dolcanatide 27 mg daily for 7 d to healthy volunteers did not activate GUCY2C, quantified as accumulation of its product cyclic GMP, in epithelial cells of the distal rectum. These data reveal that the enhanced stability of dolcanatide, with persistence along the rostral-caudal axis of the small and large intestine, is inadequate to regulate GUCY2C across the colorectum to prevent tumorigenesis. These results highlight the importance of developing a GUCY2C agonist for cancer prevention formulated for release and activity targeted to the colorectum.