CIN-103 for Irritable Bowel Syndrome

Recruiting in Palo Alto (17 mi)

+52 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: CinPhloro Pharma, LLC

Must not be taking: Antibiotics

Disqualifiers: Inflammatory bowel disease, Celiac, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate if the study drug, CIN-103, can help reduce the symptoms associated with irritable bowel syndrome with predominant diarrhea (IBS-D) in adult patients. The main questions it aims to answer are: * To evaluate the efficacy of CIN-103 on symptoms of IBS-D when given to patients with IBS-D compared to a placebo. * To evaluate the safety and tolerability of CIN-103 when given to patients with IBS-D compared to a placebo Participants will attend the following visits: * Screening Period (1 Visit) * Baseline Period (1 Visit) * Will complete daily diary and other Patient Reported Outcomes (PROs) as described in the protocol to assess eligibility for continued participation. * 12-Week Treatment Period (5 Visits) * Study drug taken twice daily by mouth. * Will complete daily diaries and other PROs as described in the protocol. * Follow- Up Period (1 Visit) Researchers will compare CIN-103 Dose 1, CIN-103 Dose 2, and placebo, to evaluate the clinical response to multiple dose strengths of CIN-103 relative to placebo on abdominal pain and stool consistency along with safety and tolerability.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug CIN-103 for treating Irritable Bowel Syndrome?

Research shows that phloroglucinol, a component of CIN-103, can help reduce abdominal pain and muscle spasms in people with Irritable Bowel Syndrome (IBS), especially those with diarrhea-predominant IBS. Studies indicate it can lessen the increase in gut movement after meals, which may help relieve IBS symptoms. ^{1 2 3 4 5}

Is CIN-103 (Phloroglucinol) safe for humans?

Phloroglucinol, used in treating irritable bowel syndrome, is generally considered safe, but it is important to monitor for any toxic impurities like 3,5-Dichloroaniline that can be present in the formulation. ^{1 2 3 4 6}

How is the drug CIN-103 different from other treatments for irritable bowel syndrome?

CIN-103, which contains phloroglucinol, is unique because it is an antispasmodic drug that specifically targets and relaxes smooth muscles in the gut, helping to relieve abdominal pain and spasms associated with irritable bowel syndrome. This mechanism of action is different from other treatments that may focus on altering gut bacteria or reducing inflammation. ^{1 2 3 4 7}

Research Team

Eligibility Criteria

Adults over 18 with IBS-D who have a stable diet and aren't planning lifestyle changes that could affect their symptoms. They should have a BMI between 18-40, normal colon cancer screening results based on age, and no significant history of colorectal polyps or other conditions that might interfere with the study.

Inclusion Criteria

In the last 6 months when having a bowel movement, do you have abdominal pain associated with the change in frequency of your stool?

In the last 6 months have you had abdominal pain that's related to a bowel movement?

Have a serum tTG-IgA (tissue transglutaminase immunoglobulin A) ≤ 3 U/mL at the Screening Visit;

Exclusion Criteria

You have been diagnosed with Congestive Heart Failure

You have been diagnosed with Immunocompromised

Do you have any current or a history of diverticulitis, blood in stool, or unexplained GI bleeding in the last 3 months?

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline

Participants complete daily diary and other Patient Reported Outcomes (PROs) to assess eligibility for continued participation

1 visit

1 visit (in-person)

Treatment

Participants receive the study drug CIN-103 or placebo twice daily by mouth for 12 weeks, with daily diaries and other PROs

12 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 visit

1 visit (in-person)

Treatment Details

Interventions

• CIN-103 (Other)

Trial Overview The trial is testing CIN-103 against a placebo to see if it reduces IBS-D symptoms like abdominal pain and diarrhea. Participants will take the drug or placebo twice daily for 12 weeks and track their symptoms in diaries.

Participant Groups

Group I: CIN-103 BID Dose 2 Experimental Treatment 1 Intervention

CIN-103 Dose 2, administered as 4 x CIN-103 capsules per dose. Two doses per day.

Group II: CIN-103 BID Dose 1 Experimental Treatment 1 Intervention

CIN-103 Dose 1, administered as 2 x CIN-103 capsules and 2 x matching placebo per dose. Two doses per day.

Group III: Placebo for CIN-103 BID Placebo Group 1 Intervention

Placebo for CIN-103, administered as 4 x matching placebo capsules per dose. Two doses per day.

Who Is Running the Clinical Trial?

CinPhloro Pharma, LLC

Lead Sponsor

Trials

1

Recruited

450+

Findings from Research

In a study of 100 patients with Irritable Bowel Syndrome (IBS), phloroglucinol was found to significantly improve various symptoms such as abdominal pain, stool frequency, urgency, and bloating over a two-month treatment period.

Phloroglucinol was well tolerated, with a notable improvement in symptoms for females regarding the sense of incomplete defecation, while no significant effect was observed for straining in both genders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phloroglucinol in irritable bowel syndrome. Jafri, W., Yakoob, J., Hussain, S., et al.[2015]

In a study of 72 patients with diarrhea-predominant irritable bowel syndrome (IBS-D), phloroglucinol showed a significant improvement in overall IBS symptoms compared to placebo over a 3-week period, with 61.6% of patients responding positively versus 30.6% in the placebo group.

Phloroglucinol was found to be safe, with no serious adverse events reported, suggesting it could be a beneficial treatment option for managing IBS-D symptoms, although further large-scale studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Phloroglucinol in Patients With Diarrhea-predominant Irritable Bowel Syndrome: A Randomized, Double-blind, Placebo-controlled Trial. Shin, SY., Cha, BK., Kim, WS., et al.[2022]

In a study involving 307 patients with irritable bowel syndrome, treatment with phloroglucinol/trimethylphloroglucinol for one week resulted in a significant reduction in abdominal pain intensity compared to placebo, with a 57.8% decrease in pain intensity versus 46.3% in the placebo group.

The treatment also led to a higher percentage of patients experiencing at least a 50% reduction in pain (62% in the treatment group vs. 47% in the placebo group), indicating its efficacy as an antispasmodic agent for managing acute pain exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol. A randomized, double-blind, placebo-controlled study. Chassany, O., Bonaz, B., Bruley DES Varannes, S., et al.[2018]

This study introduces novel spectrophotometric methods to simultaneously measure phloroglucinol (PHG) and trimethylphloroglucinol (TMG) in the presence of the toxic impurity 3,5-dichloroaniline (DCL), ensuring safety in pharmaceutical formulations.

The proposed methods demonstrated comparable accuracy to traditional HPLC techniques for assessing drug content and uniformity in dosage forms, highlighting their reliability and potential for routine quality control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced Spectrophotometric Resolution Techniques for a Spectrally Overlapping Spasmolytic Binary Mixture along with Dichloroaniline as a Toxic Impurity: Application to Content Uniformity Testing. Darweish, E., Marzouk, HM., Fayez, YM., et al.[2022]

In a study of 20 patients with irritable bowel syndrome, phloroglucinol significantly reduced the post-meal increase in rectosigmoid motor activity compared to a placebo, suggesting its potential efficacy in managing abdominal pain associated with this condition.

The results indicate that phloroglucinol may help alleviate symptoms by dampening the motor response of the intestines after eating, which could be beneficial for patients experiencing postprandial abdominal pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of phloroglucinol on rectosigmoid motility stimulated by a test meal. Study in patients with irritable bowel syndrome]. Cargill, G., Salin, B., Lubin, S., et al.[2016]

A review of 42 trials on lactic acid bacteria (LAB) for treating irritable bowel syndrome (IBS) found that 34 trials reported beneficial effects on symptoms, indicating potential efficacy, but results varied widely in magnitude and outcomes.

Concerns about trial design, including strain selection and dosage, highlight the need for better research methods to ensure safety and long-term tolerability of LAB treatments for IBS, suggesting that future studies should focus on understanding the microbiota's role in health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: probiotics for the treatment of irritable bowel syndrome--focus on lactic acid bacteria. Clarke, G., Cryan, JF., Dinan, TG., et al.[2013]

A review of three randomized controlled trials (RCTs) found that phloroglucinol, an anti-spasmodic drug, showed no significant superiority over placebo in treating abdominal pain, with a risk ratio of 1.10 and no statistical significance.

Only one of the RCTs indicated a potential benefit of phloroglucinol, but it had a high risk of bias, suggesting that there is insufficient evidence to support its widespread use for abdominal pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of phloroglucinol for treatment of abdominal pain: a systematic review of literature and meta-analysis of randomised controlled trials versus placebo. Blanchard, C., Pouchain, D., Vanderkam, P., et al.[2018]

References

1. Pakistan pubmed.ncbi.nlm.nih.gov

Phloroglucinol in irritable bowel syndrome. [2015]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

The Effect of Phloroglucinol in Patients With Diarrhea-predominant Irritable Bowel Syndrome: A Randomized, Double-blind, Placebo-controlled Trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol. A randomized, double-blind, placebo-controlled study. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Advanced Spectrophotometric Resolution Techniques for a Spectrally Overlapping Spasmolytic Binary Mixture along with Dichloroaniline as a Toxic Impurity: Application to Content Uniformity Testing. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Effect of phloroglucinol on rectosigmoid motility stimulated by a test meal. Study in patients with irritable bowel syndrome]. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Review article: probiotics for the treatment of irritable bowel syndrome--focus on lactic acid bacteria. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of phloroglucinol for treatment of abdominal pain: a systematic review of literature and meta-analysis of randomised controlled trials versus placebo. [2018]