Digestive System Diseases

All Conditions

Neoplasms

Ear, Nose, and Throat Diseases

Gastroesophageal Reflux

Gastrointestinal Neoplasms

Barrett Esophagus

Digestive System Neoplasms

Esophageal Motility Disorders

Esophageal Spasm, Diffuse

Deglutition Disorders

Esophageal Diseases

Gastrointestinal Diseases

Precancerous Conditions

Gastrointestinal Agents

All Drugs and Chemicals

Amino Acids

Linaclotide

Plecanatide

Tyrosine

Patients receive a single dose of plecanatide (3 mg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.

Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.

Patients undergo standard of care EGD with biopsy and luminal fluid collection.

Biopsy

Biospecimen Collection

Esophagogastroduodenoscopy

Niloy J. Samadder

Scott A. Waldman

David S. Weinberg

Howard H. Bailey

David S Weinberg

This early phase I trial studies the guanylyl cyclase C (GCC) agonist effect on cGMP signal in duodenal tissue. Plecanatide and linaclotide are drugs approved by the Food and Drug Administration for the treatment of conditions related to constipation. This trial aims to see the effects of taking either one of two drugs, plecanatide or linaclotide, or no drug, on a certain chemical found in the tissue collected from small intestine and how they compare.

PRIMARY OBJECTIVE:

I. To assess and compare participants randomly assigned 1:1:1 to one of three intervention arms (plecanatide 3 mg versus linaclotide 145 mcg versus no active agent) with respect to change in cyclic guanosine monophosphate (cGMP) accumulation in normal appearing duodenal mucosa specimens.

SECONDARY OBJECTIVES:

I. Characterization and comparison of the following outcomes (in prioritized order):

Ia. cGMP levels in luminal fluid from participants receiving either linaclotide or plecanatide to fluid from participants receiving no agent; Ib. Vasodilator stimulated phosphoprotein (VASP) phosphorylation in normal-appearing duodenal mucosa biopsy specimens from participants receiving either linaclotide or plecanatide to those specimens from participants receiving no agent.

EXPLORATORY OBJECTIVES:

I. Comparison of cGMP and VASP phosphorylation between the plecanatide and linaclotide arms.

II. Transcriptome analysis of cellular response (ribonucleic acid \[RNA\] sequencing analyses) to define whether GCC ligand exposure induces reproducible changes in duodenal messenger \[m\]RNA expression that can serve as a reliable biomarker of GCC-cGMP signaling in future studies.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive a single dose of plecanatide (3 mg) orally (PO) 60-120 minutes prior to standard of care esophagogastroduodenoscopy (EGD) with biopsy and luminal fluid collection. Patients also undergo biopsy on study.

ARM II: Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection. Patients also undergo biopsy on study.

ARM III: Patients undergo standard of care EGD with biopsy and luminal fluid collection. Patients also undergo biopsy on study.

After completion of study intervention, patients are followed up at day 7.

GCC Agonist Signal in the Small Intestine

Pilot Study of GCC Agonists to Identify a Cyclic-GMP Signal in Duodenal Tissue of Volunteers

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Transcriptome analysis of cellular response (ribonucleic acid \[RNA\] sequencing analyses), to define whether guanylyl cyclase C (GCC) ligand exposure induces reproducible changes in duodenal messenger (m)RNA expression that can serve as a reliable biomarker of GCC-cGMP signaling in future studies.

Will compare cGMP levels measured in normal-appearing duodenal mucosa biopsy specimens from participants receiving linaclotide or plecanatide to cGMP levels in specimens from participants receiving no active treatment. Will evaluate the difference between the control and each treated arm in cGMP levels using two-tailed two-sample Student t-tests. If necessary, a log transformation or Wilcoxon rank-sum will be used, as appropriate.

National Cancer Institute (NCI)

Symptoms and General Pathology

Substance Related Disorders

Behaviors and Mental Disorders

Rare Diseases

Constipation

Pain

Opioid-Induced Constipation

Signs and Symptoms, Digestive

Narcotic-Related Disorders

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Chronic Graft Versus Host Disease

Analgesics

Central Nervous System Depressants

Analgesics, Opioid

Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.

Linaclotide 145 micrograms

Linaclotide 290 micrograms

Placebo

Patricia D'Astoli, RN

The purpose of this study was to evaluate the safety and efficacy of linaclotide for the treatment of opioid-induced constipation (OIC), in adults receiving stable opioid treatment for chronic non-cancer pain that has been present for a minimum of 3 months.

This study included up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Patients meeting the entry criteria were randomized to 1 of 2 doses of linaclotide or placebo once per day for 8 weeks. This 8-week study assessed the effects of linaclotide on bowel movement frequency, as well as other bowel symptoms of OIC.

Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered Orally for 8 Weeks to Adult Outpatients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.

The median time to the first SBM after the first dose of investigational product

A 6/8 Week SBM 3 + 1 responder was a participant who met the weekly SBM 3 + 1 responder criteria for at least 6 out of the 8 weeks of the Treatment Period. For each week in the Treatment Period, a weekly SBM 3 + 1 responder was a patient who had an SBM weekly rate ≥ 3 and an increase ≥ 1 in the SBM weekly rate from baseline for that week.

Stool Consistency was assessed using the 7-Point Bristol Stool Form Scale:

1. = separate hard lumps like nuts (difficult to pass)
2. = sausage shaped but lumpy
3. = like a sausage but with cracks on surface
4. = like a sausage or snake, smooth and soft
5. = soft blobs with clear-cut edges (passed easily)
6. = fluffy pieces with ragged edges, a mushy
7. = watery, no solid pieces (entirely liquid)

Straining was measured on a 5-point ordinal scale where a value of 1 is "not at all" and a value of 5 is "an extreme amount."

Abdominal bloating was collected daily via IVRS calls and measured using an 11-point numerical rating scale, where 0 represents no abdominal bloating and 10 represents very severe abdominal bloating.

Ironwood Pharmaceuticals, Inc.

Forest Laboratories

Linaclotide 145 Micrograms

Linaclotide 290 Micrograms

Total

Age, Continuous

Age, Customized

Sex/Gender, Customized

Race

Race/Ethnicity, Customized

Ethnicity

Weight

Height

Body Mass Index (BMI)

Number of spontaneous bowel movements (SBMs) per week

SBM Frequency Rate

Of the 254 participants who were randomized to treatment, 2 patients were randomized in error and did not receive investigational product. 252 of the randomized participants did receive investigational product and comprise the Safety and ITT populations.

Therapeutic Area Head

252 participants received at least one dose of study drug, comprising the ITT study population.

Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week)

Time to First SBM After the First Dose of Investigational Product

Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria

Of the 252 participants in the ITT population, 200 participants had Stool Consistency data collected

Change From Baseline in 8-Week Stool Consistency

Of the 252 participants in the ITT population, 200 participants had 8-week straining data collected

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
GCC Agonist Signal in the Small Intestine	NCT05107219	Barrett Esophag... Gastroesophagea... Malignant Diges...	Biopsy Biospecimen Col... Esophagogastrod... Linaclotide Plecanatide	18 Years -	National Cancer Institute (NCI)
Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain	NCT02270983	Opioid-Induced ...	Linaclotide 145... Linaclotide 290... Placebo	18 Years -	Forest Laboratories
GCC Agonist Signal in the Small Intestine	NCT05107219	Barrett Esophag... Gastroesophagea... Malignant Diges...	Biopsy Biospecimen Col... Esophagogastrod... Linaclotide Plecanatide	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for linaclotide

Every month we try and update this database with for linaclotide cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for linaclotide

Every month we try and update this database with for linaclotide cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for linaclotide cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.