Plecanatide + Linaclotide for Digestive Health

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, plecanatide and linaclotide, to determine their effects on a chemical in the small intestine related to constipation. Participants will take plecanatide, linaclotide, or no drug before a standard procedure that collects samples from the digestive tract. The researchers aim to understand how these drugs function in the body, potentially improving treatments for constipation-related conditions. Individuals scheduled for a standard esophagogastroduodenoscopy (EGD) procedure for digestive health issues and willing to provide tissue samples may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both plecanatide and linaclotide are generally safe for adults. The FDA has approved these drugs for treating constipation-related conditions.

Plecanatide, found in Trulance, was tested in several studies. Diarrhea was the most common side effect, affecting about 5% of people with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Severe diarrhea was rare, occurring in only 0.6% of patients.

Linaclotide, present in Linzess, had similar side effects. In studies, about 2% of people taking linaclotide for CIC and IBS-C experienced severe diarrhea, compared to less than 1% of those taking a placebo.

Both medications carry warnings about the risk of severe dehydration in children, but this trial is for adults. Overall, these drugs are well-tolerated in adults, with diarrhea being the most common side effect to monitor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about linaclotide and plecanatide because they offer a novel approach to managing digestive health issues like chronic constipation and irritable bowel syndrome with constipation (IBS-C). Unlike many standard treatments that primarily focus on stimulating bowel movement, both linaclotide and plecanatide work by enhancing fluid secretion in the intestines, making stools easier to pass. This unique mechanism of action not only helps in relieving constipation but also reduces abdominal discomfort, making them a promising alternative for those seeking more comprehensive relief.

What evidence suggests that this trial's treatments could be effective for digestive health?

Research has shown that both linaclotide and plecanatide effectively treat constipation-related conditions. In this trial, participants will receive either linaclotide or plecanatide. Linaclotide relieves constipation and stomach pain in people with irritable bowel syndrome with constipation (IBS-C). One study found that 32.4% of patients met the main treatment goal over 26 weeks. Plecanatide improves bowel movement frequency and reduces bloating and stomach pain in IBS-C patients. Clinical studies reported that 21-48% of patients taking plecanatide experienced improved bowel movement frequency, compared to 10-35% of those not taking it. Both medications have FDA approval, indicating thorough testing for effectiveness in these conditions. ^{6 7 8 9 10}

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

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]

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]

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]

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]

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]

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]

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]

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]

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 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, 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3638410/

Linaclotide (Linzess) for Irritable Bowel syndrome With ... Positive outcomes were also demonstrated in the linaclotide group over a period of 26 weeks; the FDA's co-primary endpoint was achieved by 32.4% of patients ...

2. linzesshcp.com linzesshcp.com/linzess-ibs-c-efficacy

Efficacy For Patients With IBS-C | LINZESS® (linaclotide) In pivotal studies,. LINZESS demonstrated relief of both constipation and abdominal pain in adult patients with IBS-C1. LINZESS was studied in over 1,600 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40079184

Efficacy of Linaclotide in Functional Dyspepsia and ... Conclusions: Linaclotide shows better efficacy for functional dyspepsia and constipation-predominant irritable bowel syndrome overlap compared ...

4. investor.ironwoodpharma.com investor.ironwoodpharma.com/press-releases/press-release-details/2023/Ironwood-Presents-New-Data-on-Potential-of-Linaclotide-for-Functional-Constipation-in-Children-and-Adolescents-Ages-6-17-Years-Old-at-Digestive-Disease-Week-2023/default.aspx

Ironwood Presents New Data on Potential of Linaclotide for ... Linaclotide was generally well-tolerated and exhibited a safety profile consistent with a prior pediatric Phase II study in functional ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05134584

Study Details | NCT05134584 | Efficacy of Linaclotide in ... This study aims to assess the efficacy and safety of linaclotide in patients with overlapping symptoms of both functional dyspepsia (FD) and constipation- ...

6. linzesshcp.com linzesshcp.com/linzess-ibs-c-safety

LINZESS® (linaclotide) Safety Profile Among IBS-C Patients In placebo-controlled clinical trials, 2% of the IBS-C patients treated with LINZESS reported severe diarrhea vs less than 1% in patients receiving placebo ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/202811s013lbl.pdf

4066835 This label may not be the latest approved by FDA ... WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC. PATIENTS. See full prescribing information for complete boxed warning. • LINZESS is contraindicated in ...

8. linzesshcp.com linzesshcp.com/linzess-cic-safety

LINZESS® (linaclotide) Safety Profile Among CIC Patients Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients and in <1% of 72 mcg LINZESS-treated CIC patients. In pediatric patients 6 to ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK578208/

Linaclotide - StatPearls - NCBI Bookshelf Linaclotide is an FDA-approved medication indicated for adults suffering from irritable bowel syndrome with predominant constipation (IBS-C) and chronic ...

10. linzesshcp.com linzesshcp.com/linzess-FC-safety

LINZESS® (linaclotide) Safety Profile Among FC Patients Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients and in <1% of 72 mcg LINZESS-treated CIC patients. In pediatric patients 6 to ...