Evaluation of Buspirone Hydrochloride on Esophageal Motility and Dysphagia Symptoms in Patients with Ineffective Motility or Absent Peristalsis

The primary objective of this study is to evaluate the effect of **buspirone** on high-resolution manometry parameters, specifically the distal contractile integral (DCI), in patients with poor esophageal motility. This is clinically relevant as it aims to address ineffective motility or absent peristalsis, which can significantly impact swallowing function and quality of life. The study utilizes high-resolution impedance manometry with three types of boluses to assess these effects.

Secondary objectives include:

• Investigating the effect of buspirone versus placebo on various esophageal and esophagogastric junction (EGJ) pressure flow parameters, such as PCI es., DCI, Largest Break Size, DL, IRP4s, PFI, IR, DPA, DPE, RP, CSI, BPT, BFT, EGJ Rest.P, EGJCI, and LES-CD, as measured by high-resolution impedance manometry.
• Assessing the influence of buspirone on symptom changes using the validated Mayo Dysphagia Questionnaire.
• Evaluating the influence of buspirone on changes in overall treatment evaluation (OTE) and overall symptom severity (OSS).

The clinical trial involves participants diagnosed with **ineffective motility** or absent peristalsis, focusing on individuals experiencing poor esophageal motility. The study population includes both male and female subjects, aged 18 years and older, who have reported dysphagia for a minimum duration of two months. Participants were selected based on the absence of anatomical causes for their symptoms and the exclusion of those with a hiatal hernia measuring 3 cm or more. The trial does not involve a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effect of **buspirone hydrochloride** on esophageal motility, bolus transit, and symptoms of dysphagia in patients with ineffective motility or absent peristalsis. This study is a randomized, double-blind, placebo-controlled, cross-over trial. The trial will utilize high-resolution esophageal manometry and impedance to assess the primary endpoint, which is the change in distal contractile integral (DCI) between buspirone and placebo. Secondary endpoints include changes in symptoms and various manometry parameters such as proximal contractile integral, distal latency, and esophago-gastric junction resting pressure.

The trial is expected to run from October 2019 to September 2025. Participants will be involved in the study for a maximum treatment period of four weeks. The study will include an initial screening visit to confirm eligibility based on criteria such as ineffective motility or absent contractility identified on high-resolution impedance manometry (HRiM), a primary complaint of dysphagia for at least two months, and age over 18 years. Exclusion criteria include anatomical causes for symptoms and the presence of a hiatal hernia of 3 cm or more. Sexually active women of childbearing potential must use appropriate contraception.

Following the screening, participants will undergo a series of study visits, including baseline assessments and follow-up visits to monitor the effects of the treatment. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse effects or if they do not comply with the study protocol. The trial aims to provide valuable insights into the therapeutic potential of buspirone hydrochloride for patients with esophageal motility disorders.

The clinical trial involves the administration of **Buspirone hydrochloride** as the experimental medication. Buspirone hydrochloride is provided in a **tablet** form, with each tablet containing 10 mg of the active substance. The tablets are manufactured by RIVOPHARM UK and are identified by the marketing authorization number PL 33155/0121. The route of administration is **oral use**, and the maximum daily dose is set at 60 mg, with a total maximum dose of 1700 mg over the treatment period. The treatment duration is limited to a maximum of 4 weeks. Participants' compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** treatment, which is manufactured by Laboratoria Wolfs. The placebo is formulated as a tablet, with each tablet weighing 488 mg. The ingredients per tablet include lactose monohydrate (320 mg), carmellose sodium (10 mg), corn starch (70 mg), cellulose microcrystalline (55 mg), silicium dioxide anhydrous (20 mg), and magnesium stearate (13 mg). The placebo tablets are designed to match the appearance of the buspirone hydrochloride tablets to maintain the double-blind nature of the trial. The placebo is administered orally, following the same dosing schedule as the experimental medication, to serve as a comparator in evaluating the efficacy of buspirone hydrochloride in patients with poor esophageal motility.

Efficacy in this clinical trial will be assessed by evaluating the effect of **buspirone hydrochloride** on esophageal motility in patients with poor esophageal motility. The primary endpoint for efficacy assessment is the change in distal contractile integral (DCI, mm Hg*s*cm) between buspirone and placebo, as measured by high-resolution impedance manometry (HRiM) with a liquid bolus (5 mL) in a supine position. Secondary endpoints include changes in symptoms between placebo and buspirone, assessed using a Likert score during HRiM with three types of boluses. Additional secondary endpoints involve various manometry parameters such as Proximal Contractile Integral (PCI), Distal Latency (DL), Integrated Relaxation Pressure 4s (IRP4s), and others, as well as patient-reported outcomes like the Mayo Dysphagia Questionnaire and Overall Treatment Evaluation.