Efficacy and Safety of Isosorbide Oral Solution in Patients With Meniere's Disease (MD)

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II/III Clinical Study of Isosorbide Oral Solution in the Treatment of Meniere's Disease

The purpose of this study is to evaluate the efficacy and safety of isosorbide oral solution compared with placebo in people with unilateral Meniere's disease. A total of approximately 234 subjects will be enrolled in this study: 72 subjects in phase Ⅱ and approximately 162 subjects in phase Ⅲ. Patients were randomly assigned to either the experimental group or the control group. The randomization ratios for phase Ⅱ and phase Ⅲ were 1:1 and 2:1, respectively.

Study Overview

• Status: Not yet recruiting
• Conditions: Meniere´s Disease
• Intervention / Treatment: Drug: Isosorbide oral solution; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 234
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Weijia Kong, PhD; Phone Number: 027-85726685; Email: entwjkong@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged ≥18 and ≤65 years old.
2. Patients with unilateral Meniere's disease who meet the diagnostic criteria for Meniere's disease in the Guidelines for the Diagnosis and Treatment of Meniere's Disease (2017).
3. At least 3 episodes of vertigo caused by Meniere's disease within 6 months before enrollment.
4. Those who understand and voluntarily sign the informed consent.

Exclusion Criteria:

1. Patients who have had previous ear surgery for Meniere's disease.
2. People who suffer from vertigo caused by organic lesions of the external, middle or inner ear.

3. Patients with diseases that the investigators believe may limit the subjects' participation in this trial:

   • patients with acute intracranial hematoma;
   • patients with hypokalemia (serum potassium < lower limit of normal) or severe dehydration (needing infusion, or hospitalization, or life-threatening, requiring emergency treatment);
   • patients with acute pulmonary edema;
   • patients with hypotension (systolic blood pressure <90 mmHg and/or diastolic blood pressure <60 mmHg during the screening period);
   • patients with severe cardiovascular and cerebrovascular diseases: such as New York Heart Association grade III or IV heart failure, myocardial infarction or unstable angina pectoris within the last 6 months, severe heart failure, progressive multifocal leukoencephalopathy, hypertension that is difficult to control with drugs (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥100 mmHg), etc.;
   • patients with major diseases of other important organs that affect their participation in this study.
4. Patients who need to use diuretics other than trial drugs for a long time after enrollment.

5. Patients with any of the following conditions are known or found in laboratory tests:

   • serum creatinine (Cr) level is not within the normal range;
   • human immunodeficiency virus (HIV) test is positive or has acquired immunodeficiency syndrome (AIDS);
   • active syphilis infection (positive Treponema pallidum antibody and positive non-specific syphilis antibody);
   • active hepatitis, hepatitis B: HBsAg and/or HBcAb are positive and HBV-DNA > 500 IU/mL or the lower limit of detection of the research center [only when the lower limit of detection of the research center is higher than 500 IU/mL]; hepatitis C: HCV antibody is positive and HCV-RNA is positive or greater than the upper limit of normal value.
6. Patients with known or suspected history of allergy to the investigational drug (isosorbide) and its excipients (sorbitol, lactic acid, saccharin sodium, propylparaben, butylparaben, orange flavor).
7. Those with a history of drug abuse or alcoholism within 6 months before enrollment.
8. Patients who have taken any prohibited drugs specified in this protocol for more than 1 week within 4 weeks before the first administration, including but not limited to vestibular suppressants (including antihistamines - promethazine, diphenhydramine, chlorpheniramine, etc., benzodiazepines - diazepam, lorazepam, clonazepam, etc., anticholinergics - scopolamine, atropine, glycopyrrolate, etc., and antidopamines - prochlorperazine, droperidol, etc.), betahistine, diuretics (including thiazide diuretics - hydrochlorothiazide, chlorthalidone, indapamide, indapamide sustained-release tablets, etc., loop diuretics - furosemide, torsemide, etc., potassium-sparing diuretics - amiloride, triamterene, etc.), glucocorticoids (including prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, dexamethasone, etc.).
9. Those who received intratympanic injection of gentamicin within the last year.
10. Patients who have received any other clinical trial drugs/devices within 30 days before the first dose.
11. Pregnant or lactating women, female patients or male patients' partners who plan to become pregnant during the study period and within 6 months after the last dose, and those who are unwilling to use a medically recognized effective contraceptive method (such as intrauterine contraceptive device or condom) during the trial.
12. Those who are judged by the researchers to be unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group	Drug: Isosorbide oral solution; 30 mL, TID
Placebo Comparator: Control group	Drug: Placebo; 30 mL, TID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The changes from baseline in the number of vertigo attacks due to Meniere's disease during the treatment period	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in the number of vertigo attacks caused by Meniere's disease compared with the baseline at 6 months after the first administration.		6 months after the first administration
The changes in the number of vertigo attacks caused by Meniere's disease compared with the baseline at 4-6 months after the first administration.		4-6 months after the first administration
The changes in hearing from baseline 6 months after the first dose.	The assessment was made by subtracting the average hearing threshold of the worst pure tone audiometry test in the 6 months before treatment from the average hearing threshold of the worst pure tone audiometry test in the period 1 to 6 months after the first administration of the drug.	6 months after first dose
Patient-reported outcomes (PRO) during the treatment period were assessed using the Dizziness Handicap Inventory (DHI).		3 months after the first dose
Patient-reported outcomes (PRO) during the treatment period were assessed using the Tinnitus Handicap Inventory (THI).		3 months after the first dose
Patient-reported outcomes (PRO) were assessed using the Dizziness Handicap Inventory (DHI) at 6 months after the first dose.		6 months after the first dose
Patient-reported outcomes (PRO) were assessed using the Tinnitus Handicap Inventory (THI) at 6 months after the first dose.		6 months after the first dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence and level of adverse events (AEs), serious adverse events (SAEs), abnormal laboratory test indicators, etc.		From the first dose to 30 days after the last dose
Change in tinnitus severity from baseline at 6 months after first dosing.		6 months after the first dose
The change from baseline in the number of attacks due to Meniere's disease at 12 months after the first dose.		at 12 months after the first administration
The change in hearing compared to baseline at 12 months after first dose.	The assessment was made by subtracting the average hearing threshold of the worst pure tone audiometry test in the 6 months before treatment from the average hearing threshold of the worst pure tone audiometry test in the period 7 to 12 months after the first administration of the drug.	at 12 months after the first administration
Patient-reported outcomes (PRO) were assessed using the Dizziness Handicap Inventory (DHI) at 12 months after the first dose.		at 12 months after the first dose
Patient-reported outcomes (PRO) were assessed using the Tinnitus Handicap Inventory (THI) at 12 months after the first dose.		at 12 months after the first dose
Changes in endolymphatic hydrops from baseline at 3 months after initial administration of isosorbide oral solution.		at 3 months after the first dose
Changes in endolymphatic hydrops from baseline at 6 months after initial administration of isosorbide oral solution.	Only subjects who received maintenance dosing were evaluated.	at 6 months after first dose

Collaborators and Investigators

• Sponsor: Lunan Better Pharmaceutical Co., LTD.

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: January 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Tinnitus; Hearing loss; Attack; Meniere´s disease; Isosorbide
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Endolymphatic Hydrops; Labyrinth Diseases; Meniere Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Diuretics; Natriuretic Agents; Vasodilator Agents; Diuretics, Osmotic; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: BT-YSLC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no plans to publish the findings in ICMJE journals.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No