CIN-102 for Gastroparesis

Recruiting in Palo Alto (17 mi)

+86 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: CinDome Pharma, Inc.

Disqualifiers: Non-diabetic gastroparesis, Arrhythmia, Surgery, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate if the study drug CIN-102 (deudomperidone) can help reduce the symptoms associated with diabetic gastroparesis in adult patients. The main questions it aims to answer are: * To evaluate the efficacy of CIN-102 on symptoms of gastroparesis when given to patients with diabetic gastroparesis compared to a placebo * To evaluate the safety and tolerability of CIN-102 when given to patients with diabetic gastroparesis compared to a placebo Participants will go through the following schedule: * Screening period (1-2 visits) * Lead-in period (1 visit) * Will complete a Gastric Emptying Breath Test (GEBT) * Will complete daily diary and other Patient Reported Outcomes (PROs) as described in the protocol to assess eligibility for continued study participation * 12-week treatment period (7 visits) * Study drug taken twice daily by mouth * Will complete daily diaries and other PROs as described in protocol * 1 week follow-up (1 visit) Researchers will compare the effects of the following treatments: * Drug- CIN-102 Dose 1 or 2 * Drug- Placebo

Will I have to stop taking my current medications?

The trial requires participants to stop ongoing treatment for gastroparesis before joining. If you are on a stable dose of GLP-1RA for diabetes, you may continue taking it during the study.

What data supports the effectiveness of the drug CIN-102 (Deudomperidone) for treating gastroparesis?

Research shows that domperidone, a component of CIN-102, is effective in treating gastroparesis by improving stomach emptying and reducing symptoms like nausea and vomiting. It is considered a safer alternative to metoclopramide due to fewer neurological side effects. ^{1 2 3 4 5}

Is CIN-102 (Deudomperidone) safe for humans?

Domperidone, which is similar to CIN-102, is generally considered safe for long-term use at recommended doses, but there are concerns about an increased risk of sudden cardiac death and heart rhythm problems. It is used in many countries, but in the U.S., it is not FDA-approved due to these risks. ^{3 5 6 7 8}

Research Team

Eligibility Criteria

Adults over 18 with diabetic gastroparesis can join this trial. It's not for those allergic to eggs or spirulina, with non-diabetic causes of gastroparesis, using motility agents, or with recent substance abuse issues.

Inclusion Criteria

You have been diagnosed with Gastroparesis

I am 18 years old or older.

Exclusion Criteria

Has known cause of gastroparesis other than diabetes (eg, idiopathic gastroparesis and/or gastroparesis attributed to surgery, viral illness, cancer, scleroderma, or other neurologic disorder)

I have not had a botulinum toxin injection in my pylorus in the last 6 months.

Positive drug or alcohol test result at Screening without medical explanation, or a history of alcoholism/substance abuse within 2 years prior to screening

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1-2 visits (in-person)

Lead-in

Participants complete a Gastric Emptying Breath Test (GEBT) and daily diary to assess eligibility for continued study participation

1 week

1 visit (in-person)

Treatment

Participants receive the study drug or placebo twice daily by mouth and complete daily diaries and other Patient Reported Outcomes (PROs)

12 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• CIN-102 (Deudomperidone) (Prokinetic Agent)

Trial Overview The trial tests CIN-102 (deudomperidone) at two different doses against a placebo to see if it eases diabetic gastroparesis symptoms. Participants will take the study drug orally twice daily for 12 weeks and track their symptoms.

Participant Groups

Group I: CIN-102 Dose 1 or 2 Experimental Treatment 1 Intervention

Dose 1 or 2, twice daily for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo, twice daily for 12 weeks

Who Is Running the Clinical Trial?

CinDome Pharma, Inc.

Lead Sponsor

Trials

4

Recruited

760+

Findings from Research

In a study involving 93 insulin-dependent diabetes patients, both domperidone and metoclopramide were found to be equally effective in alleviating symptoms of diabetic gastroparesis over a 4-week period.

However, domperidone was associated with significantly fewer and less severe central nervous system side effects, such as somnolence and reduced mental acuity, compared to metoclopramide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Patterson, D., Abell, T., Rothstein, R., et al.[2013]

In a study involving 748 patients with gastroparesis, those treated with domperidone (DOM) showed moderate but significant improvements in symptoms, including nausea and fullness, compared to those not receiving DOM.

The analysis highlighted that DOM therapy was particularly effective for younger patients with delayed gastric emptying, suggesting its potential as a beneficial treatment option for certain gastroparesis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium. Sarosiek, I., Van Natta, M., Parkman, HP., et al.[2023]

Domperidone is a dopamine-2 receptor antagonist that effectively acts as an antiemetic and prokinetic agent, improving stomach and small intestine motor function without causing neurological side effects due to its limited ability to cross the blood-brain barrier.

It has a strong safety profile for long-term oral use and is now available for prescription in the U.S. for treating gastroparesis and chronic nausea and vomiting, making it a valuable option for gastroenterologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone: review of pharmacology and clinical applications in gastroenterology. Reddymasu, SC., Soykan, I., McCallum, RW.[2022]

In a study of 48 patients with gastroparesis, age and specific genetic polymorphisms (notably in the ABCB1 and KCNH2 genes) were linked to the effectiveness of domperidone, suggesting that these factors could help predict patient response to treatment.

Side effects from domperidone were associated with genetic variations in the ADRA1D gene, indicating that pharmacogenetic testing could potentially guide treatment decisions to enhance efficacy and minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects. Parkman, HP., Jacobs, MR., Mishra, A., et al.[2021]

Domperidone is an effective treatment for alleviating nausea and vomiting, particularly in patients receiving cytotoxic drugs and those with chronic postprandial dyspepsia, showing superior efficacy compared to metoclopramide in some studies.

Unlike many other antiemetics, domperidone has a lower risk of causing extrapyramidal side effects, making it a safer option for patients, including children, and those on anti-Parkinsonian medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Brogden, RN., Carmine, AA., Heel, RC., et al.[2018]

Domperidone is effective as a second-line treatment for gastroparesis by enhancing gastric emptying through dopamine-2 receptor inhibition, but it is not FDA-approved in the U.S. due to safety concerns.

The use of domperidone is associated with serious side effects, including risks of sudden cardiac death and ventricular arrhythmia, leading to its controversial status despite its common use in Canada and Europe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of domperidone in gastroparesis and lactation. Phan, H., DeReese, A., Day, AJ., et al.[2014]

Domperidone is an effective treatment for gastroparesis, but health regulatory agencies have raised concerns about its potential link to an increased risk of sudden cardiac death, particularly at higher doses.

No randomized controlled trials have definitively shown that domperidone increases the risk of sudden cardiac death, but observational studies suggest a possible dose-related risk, indicating that its use in patients undergoing dialysis should be carefully evaluated on an individual basis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone-associated sudden cardiac death in the general population and implications for use in patients undergoing hemodialysis: a literature review. Makari, J., Cameron, K., Battistella, M.[2019]

In a study of 115 patients with refractory gastroparesis treated with domperidone, 69% reported symptom improvement, particularly in postprandial fullness, nausea, and vomiting, indicating its efficacy in managing these symptoms.

While 12% of patients experienced side effects severe enough to stop treatment, the overall benefits of domperidone for many patients suggest it is a valuable option for managing gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort. Schey, R., Saadi, M., Midani, D., et al.[2018]

References

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

A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. [2013]

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

Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium. [2023]

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

Domperidone: review of pharmacology and clinical applications in gastroenterology. [2022]

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

Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects. [2021]

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

Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. [2018]

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

The dual role of domperidone in gastroparesis and lactation. [2014]

7. Canada pubmed.ncbi.nlm.nih.gov

Domperidone-associated sudden cardiac death in the general population and implications for use in patients undergoing hemodialysis: a literature review. [2019]

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

Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort. [2018]