E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047340 |
E.1.2 | Term | Vertigo |
E.1.2 | System Organ Class | 10013993 - Ear and labyrinth disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10022398 |
E.1.2 | Term | Inner ear signs and symptoms |
E.1.2 | System Organ Class | 10013993 - Ear and labyrinth disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To prove non-inferiority in terms of efficacy for the test product (betahistine PR 48 mg once daily) with that of reference product (Betaserc IR 24 mg twice daily) for treatment of patients with Meniere’s disease (symptoms of which may include nausea and vomiting, tinnitus and hearing loss) |
|
E.2.2 | Secondary objectives of the trial |
To confirm betahistine efficacy in vertigo and its associated symptoms of Meniere's disease and monitor safety of the participants, who are exposed to the Investigational Medicinal Products. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or non-pregnant female patients ≥18 years of age. 2. 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. 3. Patient has experienced active vertigo of significant severity during the month prior to inclusion in the trial. Significant severity is defined as a naïve patient with a first episode classified as severe with a minimum score of 7 points according to the GISFaV self-rating scale: -Intensity (V): 2 points = severe -Duration (D): 3 points = some hours -Frecuency of the crisis (F): 2 points = weekly or a pretreated patient with Betaserc IR 24 mg with severe episodes as defined before despite treatment (non-responders). 4. Patient has documented asymmetric sensorineural hearing loss. 5. Patients currently on a low salt diet at the time of screening agree to continue this low-salt diet throughout the study. 6. Patients who withdrawal of interfering concomitant therapies at least 7 days before the start of the study treatment. 7. 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. 8. Informed consent as obtained in Section 11.3 of the protocol. |
|
E.4 | Principal exclusion criteria |
1. Patient is pregnant or lactating. 2. Patient has a history of immunodeficiency disease. 3. Patient has a history of previous endolymphatic sac surgery. 4. Patient has a history of previous use of intratympanic (IT) gentamicin in the affected ear. 5. History of tympanostomy tubes with evidence of perforation or lack of closure. 6. Patient has experienced an adverse reaction to IT injection of steroids. 7. Patient has used an investigational drug or device in 3 months prior to screening. 8. Patients with hypersensitivity to the active substance or to any of the excipients of the study drug. 9. Patients with pheochromocytoma. 10. Patient with middle or inner ear infection. 11. Patient with history or presence of significant alcoholism or drug abuse in the past one year. 12. Patients with psychiatric or significant neurological disorders, spinal cord damage, use of any other agents for Meniere's disease. 13. Patients with ear surgery for vestibular disorders. 14. Patients with peptic ulcer (including a history of this disorder). 15. Patients with asthmatic bronchitis, bronchial asthma, urticaria, exanthema or allergic rhinitis. 16. Patients with pronounced hypotension. 17. Patients receiving any other agents for peripheral vestibular vertigo such as diuretics, trans tympanic gentamycin, cinnarizine, competitive antagonist of histamine, blocking H1- histamine receptors. - Patients: • on current treatment with nti-vertigo drugs • on current treatment withdrugs that act on cerebral circulation, antihistamines, calcium antagonists, antiagregant, thiazide diuretics, corticosteroids and benzodiazepines, • with any major medical or surgical condition likely to interfere with the absorption, distribution, metabolism or excretion of the drug used in the study • with a terminal disease.. 18. 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of significant responders defined by 1-point change in any two of intensity, duration and frequency of vertigo attacks score based on GISFaV scale against baseline score. - GISFaV self-rating scale [12] involving each item separately for determination of the disturbance stage of vertigo using values of intensity (V), duration (D) and associated symptoms (N), frequency of crisis (F), quality of life (Q) scored respectively by; - A four-point scale (V: 0 =absent, 1= mild, 2= severe, 3= disabling), - A five-point scale (D: 0= none, 1=<1 min, 2=<15 min, 3= some hours, 4=≥1 day) and - A three-point scale (N: 0= absent, 1= nausea, 2= vomiting); - Frequency of the crisis (F: 0=absent or sporadic, 1=monthly, 2=weekly, 3=daily, 4=multi-day) - Quality of life (Q: 0=normal, 1=partial inactivity, 2= total inactivity) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
-Number of asymptomatic days (no vertigo attacks) during treatment period. -Patient rates with all the GISFaV items equal to 0 at 3 months. -Change in number of monthly vertigo attacks during treatment period. -The Dizziness Handicap Inventory (DHI) rating scale [13] for the identification of the difficulties that patients encounter during the vertiginous disease. -Hearing will be scored as: 'good', 'slightly impaired', 'moderately impaired' or 'seriously impaired'. In addition, the patient will be asked to note whether s/he felt that her/his hearing was 'better', 'the same' or 'worse' than the week before or was 'fluctuating [16]'. -Tinnitus will be scored as: 'none', 'mild', 'moderate' or 'severe'. -Pressure sensation will be scored as 'none', 'mild', 'moderate' or 'severe'. -At the end of the study, the investigators’ and patients’ overall judgments respectively on treatment efficacy and acceptance (five-point scale: 0= null, 1= poor, 2= moderate, 3= good, 4= very good) and the doctor’s preparedness to treat the patient again with the same treatment. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |