Naronapride for Gastroparesis

(MOVE-IT Trial)

Recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dr. Falk Pharma GmbH

Disqualifiers: Gastrointestinal surgery, Botulinum injection, Gastric stimulator, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 0

Duration: 12 weeks

320 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double-blind, randomized, multicenter, placebo-controlled, comparative phase II dose-finding trial. The trial will be conducted with four treatment groups in the form of a parallel group comparison and will serve to compare oral treatment with daily doses of 10, 20, or 40 mg Naronapride vs. placebo for the treatment of patients with Gastroparesis.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have diabetes, you must have controlled diabetes with stable antidiabetic medication.

What data supports the idea that the drug Naronapride for Gastroparesis is an effective treatment?

The available research does not provide specific data on the effectiveness of Naronapride for Gastroparesis. Instead, it discusses other treatments like domperidone and prucalopride. Domperidone has been used successfully for gastroparesis, showing better results than a placebo, but it has safety concerns. Prucalopride has been shown to improve the rate at which the stomach empties, which can help with gastroparesis symptoms. However, there is no direct information on Naronapride's effectiveness in the provided research. ^{1 2 3 4 5}

What safety data exists for Naronapride in treating gastroparesis?

The provided research does not contain specific safety data for Naronapride (also known as ATI-7505) in the treatment of gastroparesis. The articles focus on other treatments like domperidone and metoclopramide, discussing their safety profiles and side effects. To find safety data for Naronapride, one would need to look for clinical trials or studies specifically evaluating Naronapride or ATI-7505. ^{3 5 6 7 8}

Is the drug Naronapride a promising treatment for gastroparesis?

Naronapride, also known as ATI-7505, is considered a promising drug for gastroparesis because it offers hope for better treatment options. Current treatments like metoclopramide have limitations and side effects, so new drugs like Naronapride are eagerly anticipated for their potential to improve symptoms and safety for patients. ^{1 2 8 9 10}

Eligibility Criteria

Adults aged 18-75 with gastroparesis, confirmed by a breath test showing delayed gastric emptying. They must have had symptoms like nausea or bloating for at least 3 months and have a BMI between 16 and 35. People with diabetes can join if their condition is stable (HbA1c ≤11%). Those with any mechanical blockages in the stomach or previous surgeries that could affect results are not eligible.

Inclusion Criteria

I am between 18 and 75 years old.

Body Mass Index (BMI) ≥16 and <35 kg/m2

Evidence of delayed gastric emptying by 13C-spirulina gastric emptying breath test (GEBT) for solids with gastric emptying T1/2 ≥ 85.33 minutes during the screening phase

Exclusion Criteria

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

Gastric stimulator implant

I have had major surgery on my digestive system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily doses of 10, 20, or 40 mg Naronapride or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Naronapride
• Placebo

Trial Overview This study tests different doses of Naronapride (10, 20, or 40 mg) against a placebo to see which works best for gastroparesis. Participants will be randomly assigned to one of these four groups without knowing which one they're in—a process known as double-blind.

Participant Groups

Group I: Naronapride 40 mg Experimental Treatment 1 Intervention

Group II: Naronapride 20 mg Experimental Treatment 1 Intervention

Group III: Naronapride 10 mg Experimental Treatment 1 Intervention

Group IV: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Dr. Falk Pharma GmbH

Lead Sponsor

Trials

46

Recruited

9,400+

Findings from Research

Aprepitant, a neurokinin-1 receptor antagonist, was successfully used to treat refractory nausea in a 41-year-old female patient with idiopathic gastroparesis, leading to significant symptom relief within 48 hours and improved quality of life over two months.

Despite aprepitant not being approved for gastroparesis-related nausea, the patient experienced no adverse effects and was able to reduce her need for intravenous hydration, suggesting potential cost-effectiveness and warranting further research into its use for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastroparesis-associated refractory nausea treated with aprepitant. Fahler, J., Wall, GC., Leman, BI.[2018]

In a phase 1 trial with 12 healthy males, the co-administration of itraconazole significantly increased the levels of trazpiroben in the body, indicating that trazpiroben's pharmacokinetics can be affected by other medications.

Trazpiroben showed no clinically relevant safety issues, suggesting it may have a better safety profile compared to other treatments for gastroparesis, like domperidone, especially regarding cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Pharmacokinetics of Trazpiroben (TAK-906), a Peripherally Selective D2/D3 Dopamine Receptor Antagonist, in the Presence and Absence of Itraconazole, a Potent CYP 3A4 Inhibitor. Chen, C., Zhang, W., Bari, M., et al.[2022]

Domperidone is an effective treatment for gastroparesis, showing superior efficacy compared to placebo and other available therapies, despite its controversial status in the US due to safety concerns.

Although there are safety concerns regarding cardiac toxicity associated with domperidone, the evidence on this issue is not convincing, suggesting that its benefits may outweigh the risks for patients with gastrointestinal motility disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making a case for domperidone in the treatment of gastrointestinal motility disorders. Ahmad, N., Keith-Ferris, J., Gooden, E., et al.[2013]

In a study of 34 patients with gastroparesis, prucalopride significantly improved symptoms and quality of life, as measured by the Gastroparesis Cardinal Symptom Index and other assessments, compared to placebo.

Prucalopride also enhanced gastric emptying rates, reducing the gastric half-emptying time from 143 minutes to 98 minutes, indicating its efficacy in treating gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study. Carbone, F., Van den Houte, K., Clevers, E., et al.[2020]

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]

Metoclopramide is currently the only FDA-approved medication for treating gastroparesis, but it carries a significant risk of side effects, including tardive dyskinesia, which can occur in up to 15% of patients.

This review aims to clarify how metoclopramide works to alleviate gastroparesis symptoms while also assessing its clinical efficacy and the associated risks, particularly focusing on strategies to reduce complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoclopramide in the treatment of diabetic gastroparesis. Lee, A., Kuo, B.[2022]

Domperidone is a new anti-nauseant that effectively reduces nausea and vomiting without causing common side effects like extrapyramidal symptoms or adrenolytic effects, making it safer than many existing anti-emetics.

Clinical trials have demonstrated that domperidone not only alleviates nausea but also enhances gastric emptying motility, proving to be an effective treatment for both adults and children suffering from dyspepsia or vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone, a novel and safe gastrokinetic anti-nauseant for the treatment of dyspepsia and vomiting. Reyntjens, AJ., Niemegeers, CJ., Van Nueten, JM., et al.[2014]

Metoclopramide is the only FDA-approved medication for diabetic gastroparesis, effectively improving gastric emptying and reducing nausea by acting as a dopamine receptor antagonist, but it has significant side effects including the risk of tardive dyskinesia with prolonged use.

Due to its potential for serious side effects, particularly when used for more than 12 weeks, there is a strong need for new treatments for gastroparesis that offer better safety and efficacy profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoclopramide for the treatment of diabetic gastroparesis. Shakhatreh, M., Jehangir, A., Malik, Z., et al.[2020]

In a study involving 10 patients with diabetes and moderate-to-severe gastroparesis, TZP-101 significantly improved gastric emptying times, reducing solid meal half-emptying by 20% and latency times by 34% compared to placebo.

TZP-101 was well-tolerated with mostly mild and self-limiting adverse events, indicating a favorable safety profile for this ghrelin agonist in treating gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Ejskjaer, N., Vestergaard, ET., Hellström, PM., et al.[2012]

In a 4-week trial involving 126 patients with chronic nausea and vomiting due to gastroparesis, aprepitant did not significantly reduce nausea severity compared to placebo, indicating limited efficacy as a primary treatment for this symptom.

However, aprepitant showed significant improvements in secondary outcomes, such as reductions in overall symptom severity and vomiting frequency, suggesting it may still provide some benefits for patients with gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders. Pasricha, PJ., Yates, KP., Sarosiek, I., et al.[2019]

References

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

Gastroparesis-associated refractory nausea treated with aprepitant. [2018]

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

Evaluation of the Pharmacokinetics of Trazpiroben (TAK-906), a Peripherally Selective D2/D3 Dopamine Receptor Antagonist, in the Presence and Absence of Itraconazole, a Potent CYP 3A4 Inhibitor. [2022]

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

Making a case for domperidone in the treatment of gastrointestinal motility disorders. [2013]

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

Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study. [2020]

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

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

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

Metoclopramide in the treatment of diabetic gastroparesis. [2022]

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

Domperidone, a novel and safe gastrokinetic anti-nauseant for the treatment of dyspepsia and vomiting. [2014]

8. England pubmed.ncbi.nlm.nih.gov

Metoclopramide for the treatment of diabetic gastroparesis. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. [2012]

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

Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders. [2019]