Evaluation of Efficacy and Safety of Betahistine Dihydrochloride PR 48 mg vs. IR 24 mg in Adult Menière's Disease: A Multicenter, Double-Blind, Parallel-Group Study

Trial ID: 2024-518347-38-00
Protocol: 0796-19
Sponsor: Intas Pharmaceuticals Limited

Trial statistics

science

test molecules

location_city

research sites

public

country

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Meniere's disease

Objectives

The primary objective of this study is to demonstrate the **non-inferiority** in terms of efficacy of a prolonged-release formulation of betahistine (48 mg once daily) compared to a conventional release formulation (Betaserc 24 mg twice daily) in the treatment of adult patients with **Menière's disease**. This condition is characterized by symptoms such as nausea, vomiting, tinnitus, and hearing loss. Establishing non-inferiority is clinically relevant as it may offer a more convenient dosing regimen for patients while maintaining therapeutic effectiveness.

Secondary objectives include confirming the efficacy of betahistine in alleviating vertigo and its associated symptoms in Menière's disease, as well as monitoring the safety of participants exposed to the investigational medicinal products. These objectives are crucial for ensuring both the therapeutic benefits and safety profile of the treatment in a real-world setting.

Participants

The clinical trial focuses on evaluating the efficacy of a test product for the treatment of **Menière's disease**. The study population includes both male and non-pregnant female participants aged 18 years and older. Participants are required to have a diagnosis of unilateral definite Menière's disease according to the 1995 American Academy of Otolaryngology — Head and Neck Surgery criteria, with a history of frequent vertigo attacks. The trial includes both naïve patients and those pretreated with betahistine IR at varying dosages. Participants must have documented asymmetric sensorineural hearing loss and adhere to a low-salt diet throughout the study. The trial excludes vulnerable populations and requires participants to discontinue interfering concomitant therapies at least seven days before the study begins. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, **double-dummy**, parallel-group study to evaluate the efficacy and safety of a prolonged-release formulation of **betahistine dihydrochloride** 48 mg once daily compared to a conventional release formulation of betahistine 24 mg taken twice daily. The trial targets adult patients diagnosed with **Menière's disease**. The primary objective is to demonstrate the non-inferiority of the test product in terms of efficacy compared to the reference product. The trial is expected to run until December 31, 2026, with recruitment having commenced on June 8, 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and history of vertigo attacks. Following successful screening, participants will be randomized into one of the two treatment arms. The study will include regular follow-up visits to monitor the participants' response to treatment, assess any adverse events, and ensure compliance with the study protocol. The end-of-study visit will conclude the trial for each participant, during which final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected duration of participant involvement is approximately 13 weeks, corresponding to the maximum treatment period. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or choose to withdraw consent. The primary endpoint focuses on the percentage of significant responders, defined by a maximum increase of one point in two of the intensity, duration, or frequency of vertigo attacks based on the GISFaV scale. Secondary endpoints include the number of asymptomatic days, changes in the number of monthly vertigo attacks, and assessments of hearing and tinnitus severity.

Treatment

The clinical trial involves the evaluation of two formulations of **betahistine dihydrochloride** for the treatment of Menière's disease. The experimental medication is a **prolonged-release tablet** containing 48 mg of betahistine dihydrochloride, manufactured by Intas Pharmaceuticals Limited. This formulation is administered orally once daily. The maximum daily dose is 48 mg, and the treatment period extends up to 13 weeks. The prolonged-release formulation aims to maintain therapeutic drug levels over an extended period, potentially improving patient compliance and therapeutic outcomes.

The comparator treatment in this study is the conventional release formulation, marketed as **BETASERC 24 mg, comprimé**, produced by Viatris Medical. This formulation is also administered orally but requires a dosage of 24 mg taken twice daily, resulting in a total daily dose of 48 mg. The treatment duration for this formulation is similarly set at 13 weeks. The conventional release formulation is designed to provide immediate release of the active substance, necessitating more frequent dosing to maintain therapeutic levels.

Both formulations contain the active substance **betahistine dihydrochloride**, a chemical compound classified under the ATC code N07CA01. The study is designed to assess the non-inferiority of the prolonged-release formulation compared to the conventional release formulation in terms of efficacy and safety. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial is conducted in a double-blind, double-dummy, parallel-group design to maintain the integrity of the study outcomes.

Efficacy

The clinical trial aims to assess the efficacy of a prolonged-release formulation of **betahistine dihydrochloride** (48 mg once daily) compared to a conventional release formulation (24 mg twice daily) in adult patients with Menière's disease. Efficacy will be primarily evaluated using the GISFaV self-rating scale, which measures the intensity, duration, and frequency of vertigo attacks. The primary endpoint is the percentage of significant responders, defined as patients who show a maximum increase of 1 point in two of the intensity, duration, or frequency scores against the baseline. Secondary endpoints include the number of asymptomatic days, changes in the number of monthly vertigo attacks, and the use of rescue medications during the treatment period. Additional assessments involve the Dizziness Handicap Inventory (DHI) rating scale, hearing and tinnitus evaluations, and overall judgments on treatment efficacy and acceptance by both investigators and patients. The trial is designed to prove non-inferiority in terms of efficacy for the test product compared to the reference product.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Male or non-pregnant female patients ≥18 years of age.
Patient has a diagnosis of unilateral definite Meniere's disease by 1995 American Academy of Otolaryngology — Head and Neck Surgery (AAOHNS) criteria and reports history of frequent attacks of active vertigo on betahistine (soon after the start of an acute attack of vertigo) prior to the study lead-in/wash-out period
Patient as • a naïve patient who has experienced active vertigo of significant severity (defined as a score ≥7 points according to Intensity (V), Duration (D) and Frequency of the crisis (F) ítems of the GISFaV self-rating scale) during the month prior to inclusion in the trial • or a pretreated patient with betahistine IR <48 mg/day who has experienced active vertigo of significant severity (defined as a score ≥5 points according to Intensity (V), Duration (D) and Frequency of the crisis (F) ítems of the GISFaV self-rating scale) during the month prior to inclusion in the trial • or a pretreated patient with betahistine IR = 48 mg/day who has experienced active vertigo of any severity during the month prior to inclusion in the trial
Patient has documented asymmetric sensorineural hearing loss.
Patients currently on a low salt diet at the time of screening agree to continue this low-salt diet throughout the study.
Patients who withdrawal of interfering concomitant therapies at least 7 days before the start of the study treatment. The following are considered concomitant therapies: other agents for peripheral vestibular vertigo (diuretics, trans tympanic gentamycin, cinnarizine, competitive antagonist of histamine, blocking H1- histamine receptors), drugs that act on cerebral circulation, antihistamines, calcium antagonists, antiagregant, thiazide diuretics, corticosteroids and benzodiazepines.
Women with child-bearing potential should have a negative serum pregnancy test at screening visit at the start of the treatment. Such females and their partners should be ready to adopt required measures to avoid conception throughout the study participation. Detailed information in section 8.1.7
Informed consent as obtained in Section 11.3 of the protocol.

cancel

Exclusion Criteria

Patient is pregnant or lactating.
Patient with middle or inner ear infection.
Patient with history of middle or inner ear surgery.
Paciente con antecedentes o presencia de alcoholismo significativo o abuso de drogas en el último año.
Patients with psychiatric or significant neurological disorders, spinal cord damage, use of any other agents for Meniere's disease.
Patients with ear surgery for vestibular disorders.
Patients with peptic ulcer (including a history of this disorder).
Patient has a history of immunodeficiency disease.
Patient has a history of previous endolymphatic sac surgery.
Patient has a history of previous use of intratympanic (IT) gentamicin in the affected ear.
History of tympanostomy tubes with evidence of perforation or lack of closure.
Patient has experienced an adverse reaction to IT injection of steroids.
Patient has used an investigational drug or device in 3 months prior to screening.
Patients with hypersensitivity to the active substance or to any of the excipients of the study drug.
Patients with pheochromocytoma.
Patients with asthmatic bronchitis, bronchial asthma, urticaria, exanthema or allergic rhinitis.
Patients with pronounced hypotension.
Patients under treatment with MAO inhibitors (including MAO-B selective).
Patients with any major medical or surgical condition likely to interfere with the absorption, distribution, metabolism or excretion of the drug used in the study or with a terminal disease.
Patients with vestibular disorders other than Meniere’s disease such as benign paroxysmal positional vertigo perilymph fistula, vestibular neuronitis, viral labyrinthitis, benign paroxysmal vertigo of childhood, otosclerosis, giddiness of ischemic or neck origin together with a sensorineural hearing loss, cholesteatoma and fistula formation, disequilibrium after head injury, drug toxicity, vestibular neuroma, multiple sclerosis, cardiovascular disturbances, craniocervical dysplasia, syphilis and Cogan's syndrome