Linaclotide Acetate in Preventing Colorectal Cancer in Healthy Volunteers

NCT01950403 | Completed Phase 1 DMC

• 5 other identifiers: MAY2012-00-01NCI-2013-01788HHSN2512012000042I13-829N01CN00042
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase I trial studies the side effects and best dose of linaclotide acetate in preventing colorectal cancer in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of linaclotide acetate may prevent colorectal cancer.

Conditions

Colorectal Cancer; Healthy, no Evidence of Disease

Outcome Measures

Primary Outcomes (1)

• Dose of linaclotide acetate that produces a 60% response rate for cGMP levels in rectal tissue by radioimmunoassay (RIA)

  The pharmacological effect is measured by the arithmetic difference in mean cGMP levels before and after 7 days of linaclotide acetate in biopsies from the colonoscopy. The mean cGMP value will be calculated based on 2 biopsies from the rectum assessed at each time point. The PD response is measured by the difference in mean cGMP levels after 7 days.

  Baseline to 7 days

Secondary Outcomes (4)

• Incidence of adverse events associated with linaclotide acetate assessed using the Common Terminology Criteria for Adverse Events version 4.0

  Up to 51 days

• PD effect of linaclotide acetate on cGMP levels from the transverse colon to the cecum

  Up to 7 days

• Change in cGMP levels between all assigned doses, analyzed sequentially from the rectum, transverse colon, and cecum

  Baseline to 7 days

• PD effect on cGMP levels (Stage II)

  Up to 6 days

Other Outcomes (1)

• PD effect of linaclotide acetate on GCC signaling (i.e., VASP phosphorylation) and general proliferation (Ki67 expression)

  Up to 7 days

Study Arms (2)

Arm I (linaclotide acetate)

EXPERIMENTAL

Participants receive linaclotide acetate PO QD on days 1-7.

Drug: linaclotide acetate; Other: pharmacological study; Other: laboratory biomarker analysis

Arm II (placebo)

PLACEBO COMPARATOR

Participants receive placebo PO QD on days 1-7.

Other: placebo; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

linaclotide acetate DRUG

Given PO

Also known as: Linzess, MD-1100 Acetate, MM-416775

Arm I (linaclotide acetate)

placebo OTHER

Given PO

Also known as: PLCB

Arm II (placebo)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I (linaclotide acetate); Arm II (placebo)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (linaclotide acetate); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to sign a written informed consent document and follow study procedures
• Willingness to abstain from grapefruit juice, alcohol, and concomitant medications during study
• Willingness to employ adequate contraception for men and women of childbearing potential; acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status documented by serum follicle-stimulating hormone (FSH), and/or documentation of surgical sterilization
• Body mass index \< 35 kg/m\^2
• Willingness to provide blood and tissue specimens for research purposes
• Participants must have normal organ function and have normal laboratory findings without clinically significant findings
• Satisfactory anesthesia and intestinal preparation, with no findings of advanced adenoma, chronic inflammation, or cancer

You may not qualify if:

• Previous personal 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 non-polyposis 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
• History of celiac disease
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• Irritable bowel syndrome, chronic constipation, functional bowel disorders, or colonic motility disorder
• Any malignancy within 3 years of baseline; participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator
• Participants may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to linaclotide
• History of difficulty with colonoscopy 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
• Use of laxatives more than 3 times per week
• Intestinal motility agents, histamine-2 inverse agonists (H-2 blockers), or proton pump inhibitors

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

linaclotide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Paul Limburg

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2013
• First Posted: September 25, 2013
• Study Start: September 1, 2013
• Primary Completion: April 28, 2016
• Study Completion: February 22, 2018
• Last Updated: December 9, 2024

Record last verified: 2018-05

Locations

US (1)