Plecanatide + Linaclotide for Digestive Health

Recruiting at 4 trial locations

Overseen By Scott A. Waldman

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Must not be taking: GCC agonists, Investigational agents

Disqualifiers: Gastric surgery, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken plecanatide, linaclotide, or similar GCC agonists in the past week, and you should not be using other investigational agents within 12 weeks prior to registration.

What safety data exists for Plecanatide and Linaclotide?

Plecanatide and Linaclotide are used for treating chronic idiopathic constipation and irritable bowel syndrome with constipation. Linaclotide has been evaluated in several clinical trials, showing it is generally well tolerated, with diarrhea being the most common adverse effect. About 10% of patients discontinued Linaclotide due to gastrointestinal side effects, primarily diarrhea. There is no relevant safety data for Linaclotide during pregnancy. Plecanatide's safety profile is not detailed in the provided research, but it is used for similar conditions as Linaclotide. ^{1 2 3 4 5}

Is the drug Linaclotide, Plecanatide a promising treatment for digestive health?

The information provided does not include any details about Linaclotide or Plecanatide, so we cannot determine if they are promising treatments for digestive health based on this data. ^{6 7 8 9 10}

What data supports the idea that Plecanatide + Linaclotide for Digestive Health is an effective drug?

The available research does not provide specific data on the effectiveness of Plecanatide + Linaclotide for Digestive Health. Instead, it focuses on other treatments for pancreatic conditions, such as pancreatic enzyme replacement therapy, which has shown improvements in symptoms like diarrhea and pain in patients with pancreatic cancer. Therefore, no direct comparison or data on Plecanatide + Linaclotide is available in the provided information. ^{11 12 13 14 15}

Who Is on the Research Team?

David S. Weinberg

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are not pregnant or breastfeeding, agree to use contraception, and have an ECOG performance status of <=1. They must be scheduled for an esophagogastroduodenoscopy (EGD), willing to provide biospecimens, and haven't used GCC agonists or investigational agents recently.

Inclusion Criteria

I am not pregnant or breastfeeding and agree to use contraception during the study.

I am on long-term antiviral treatment for herpes.

I am scheduled for an EGD procedure.

Exclusion Criteria

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

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

I have had weight loss surgery in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of plecanatide or linaclotide, or no drug, followed by standard of care EGD with biopsy and luminal fluid collection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Linaclotide
• Plecanatide

Trial Overview The study examines the effects of two FDA-approved constipation drugs, plecanatide or linaclotide, on a chemical in duodenal tissue from the small intestine compared to no drug treatment. Participants will undergo biospecimen collection including biopsy during EGD.

How Is the Trial Designed?

Group I: Arm II (linaclotide, EGD) Experimental Treatment 4 Interventions

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.

Group II: Arm I (plecanatide, EGD) Experimental Treatment 4 Interventions

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.

Group III: Arm III (EGD) Active Control 3 Interventions

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

Linaclotide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Linzess for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)
• Functional constipation in pediatric patients 6 to 17 years of age

Approved in European Union as Constella for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)

Approved in Canada as Linzess for:

• Chronic idiopathic constipation
• Irritable bowel syndrome with constipation (IBS-C)
• Functional constipation in pediatric patients 6 to 17 years of age

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pancreatic enzyme substitution is primarily indicated for malabsorption in chronic pancreatic insufficiency, which occurs when the pancreas has less than 2% of its exocrine secretory capacity, leading to significant fat malabsorption and diarrhea.

In some cases, pancreatic enzyme therapy may also help control pain in chronic pancreatitis, but the effectiveness depends on proper dosage, patient compliance, and the formulation of the enzyme preparation to withstand stomach acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme substitution in pancreatic disease. Andrén-Sandberg, A.[2018]

In a study of 95 patients with upper abdominal pain suggesting pancreatic disease, camostat mesilate significantly improved dyspeptic symptoms in those with suspected mild pancreatic disease and in an equivalent group, indicating its potential efficacy as a treatment.

The treatment involved administering 200 mg of camostat mesilate three times daily for 2 weeks, and symptom severity was measured using a visual analog scale, showing notable improvements in both the suspected pancreatic disease and equivalent groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease. Sai, JK., Suyama, M., Kubokawa, Y., et al.[2021]

Pancreatic enzyme replacement therapy is a safe and effective treatment for nutrient malabsorption due to pancreatic insufficiency, significantly reducing symptoms like steatorrhea and fat malabsorption.

Current challenges in treatment include ensuring enzymes reach the duodenum without being destroyed in the stomach, and research is focused on developing new enzymes and delivery systems to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy for pancreatic insufficiency: present and future. Fieker, A., Philpott, J., Armand, M.[2022]

In a pilot study involving patients with advanced pancreatic cancer, pancreatic enzyme replacement therapy (PERT) significantly improved symptoms of malabsorption and quality of life within just one week of treatment.

Patients reported notable reductions in diarrhea, pancreatic pain, and bloating after starting PERT, indicating its potential efficacy in managing digestive symptoms associated with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of pancreatic enzyme replacement therapy for malabsorption in advanced pancreatic cancer, a pilot study. Landers, A., Brown, H., Strother, M.[2020]

The new pancreatine formulation, Panzytrat, significantly improves the duration and quality of life for patients, especially children, suffering from chronic pancreatitis and cystic fibrosis, as shown in clinical studies involving 4,557 participants.

Panzytrat has demonstrated high efficacy and safety in both open and double-blind comparative clinical studies, making it a suitable treatment for various pancreatic excretory insufficiency symptoms, including those following surgeries or oncological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of Panzytrat in the replacement therapy of exocrine pancreatic insufficiency (an analytical review)]. Karamysheva, EI., Lobanova, EG.[2007]

Plecanatide (Trulance) has been shown to be effective in treating chronic idiopathic constipation and irritable bowel syndrome with constipation, providing relief for patients suffering from these conditions.

The efficacy of plecanatide was demonstrated through clinical trials, which highlighted its ability to improve bowel movement frequency and overall gastrointestinal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plecanatide (Trulance) for Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation. Kamuda, JA., Mazzola, N.[2020]

Linaclotide (Linzess) is an effective treatment for patients suffering from irritable bowel syndrome with constipation and chronic idiopathic constipation, helping to relieve symptoms.

The medication works by increasing fluid secretion in the intestines and accelerating bowel movements, which can significantly improve the quality of life for those affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide (Linzess) for Irritable Bowel syndrome With Constipation and For Chronic Idiopathic Constipation. Thomas, RH., Allmond, K.[2022]

Linaclotide is a newly approved treatment for moderate to severe irritable bowel syndrome with constipation (IBS-C) that works by stimulating fluid secretion and increasing colonic transit in the gastrointestinal tract.

In phase III trials, linaclotide significantly improved abdominal pain and bowel function compared to placebo, with a good safety profile, although the most common side effect was diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. McCormack, PL.[2022]

Linaclotide has been shown to provide more frequent relief from constipation-related symptoms compared to a placebo in two clinical trials involving about 1600 patients, lasting 3 to 6 months.

However, it can cause significant gastrointestinal side effects, particularly diarrhea, which affected 20% of patients and led to discontinuation in about 10%, raising concerns about its safety and the lack of evidence showing it is more effective than other laxatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. [2017]

Linaclotide is effective for treating moderate to severe irritable bowel syndrome with constipation, showing significant improvements in symptoms compared to placebo, with a combined response rate of 12.6% to 22.8%.

The only notable adverse effect of linaclotide is diarrhea, making it a relatively safe option for patients who do not respond to other treatments for their symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity. Carballo, F.[2019]

Linagliptin is an effective treatment for type 2 diabetes that improves blood glucose control without increasing the risk of low blood sugar (hypoglycemia) or causing weight gain, making it a safe option for patients.

It has a unique pharmacokinetic profile that allows it to be used without dose adjustments in patients with renal impairment and the elderly, due to its biliary excretion and low hepatic metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Linagliptin (Trajenta): a selective DPP-4 inhibitor with limited renal elimination]. Scheen, AJ., Van Gaal, LF.[2015]

Linagliptin is an effective treatment for type 2 diabetes, leading to significant reductions in hemoglobin A1c and blood glucose levels, and can be taken at a standard dose of 5 mg daily without needing adjustments for patients with kidney or liver issues.

While linagliptin is generally well tolerated and does not cause weight gain, there is a higher risk of hypoglycemia when used with insulin secretagogues, highlighting the need for careful monitoring in such combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus. Neumiller, JJ.[2015]

Linagliptin, a DPP-4 inhibitor, has shown significant efficacy in treating type 2 diabetes, reducing glycated hemoglobin levels by 0.6% to 0.8% in over 4000 patients during Phase 3 clinical trials.

The safety profile of linagliptin is comparable to that of a placebo, making it a safe option for patients, and it maintains over 80% DPP-4 inhibition for 24 hours after dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Toth, PP.[2015]

Liraglutide-loaded PLGA nanoparticles (NPs) effectively protect the drug from gastric degradation and enhance its permeability across the intestinal barrier, showing a 1.5-fold increase in absorption compared to liraglutide solution.

The PLGA NPs demonstrated a safe transport mechanism without altering the structure of cell junctions, indicating their potential as a reliable oral delivery system for GLP-1 analogs like liraglutide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability. Ismail, R., Bocsik, A., Katona, G., et al.[2020]

Linagliptin, a DPP-4 inhibitor, effectively improves blood sugar control in adults with type 2 diabetes, even in patients with renal impairment and the elderly, without requiring dosage adjustments due to its nonrenal elimination route.

It is generally well tolerated with a low risk of hypoglycaemia and no impact on body weight, making it a suitable option for various patient groups, although further research is needed to confirm its cardiovascular and renal safety benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linagliptin: an update of its use in patients with type 2 diabetes mellitus. McKeage, K.[2022]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Enzyme substitution in pancreatic disease. [2018]

2. Japan pubmed.ncbi.nlm.nih.gov

Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy for pancreatic insufficiency: present and future. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The effectiveness of pancreatic enzyme replacement therapy for malabsorption in advanced pancreatic cancer, a pilot study. [2020]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Use of Panzytrat in the replacement therapy of exocrine pancreatic insufficiency (an analytical review)]. [2007]

6. United States pubmed.ncbi.nlm.nih.gov

Plecanatide (Trulance) for Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Linaclotide (Linzess) for Irritable Bowel syndrome With Constipation and For Chronic Idiopathic Constipation. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. [2017]

10. Spain pubmed.ncbi.nlm.nih.gov

Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity. [2019]

11. Belgium pubmed.ncbi.nlm.nih.gov

[Linagliptin (Trajenta): a selective DPP-4 inhibitor with limited renal elimination]. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus. [2015]

13. England pubmed.ncbi.nlm.nih.gov

Linagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. [2015]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability. [2020]

15. New Zealand pubmed.ncbi.nlm.nih.gov

Linagliptin: an update of its use in patients with type 2 diabetes mellitus. [2022]