A Multicenter, Two-arm, Double-blind, Double dummy, Parallel-group Study for efficacy and safety evaluation of prolonged release formulation of Betahistine PR 48 mg once daily in comparison with conventional release formulation of Betahistine IR 24 mg, twice daily in treatment of adult patients with Menière's disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intas Pharmaceuticals Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

8 Jun 2022 → ongoing

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518347-38-00

EudraCT number

2020-005246-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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).

Secondary objectives 1

1. 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.

Conditions and MedDRA coding

Menière's disease

Regulatory references

Scientific advice from competent authorities

Agencia Espanola De Medicamentos Y Productos Sanitarios

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 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
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. 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.
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.

Exclusion criteria 20

1. Patient is pregnant or lactating.
2. Patient with middle or inner ear infection.
3. Patient with history of middle or inner ear surgery.
4. Paciente con antecedentes o presencia de alcoholismo significativo o abuso de drogas en el último año.
5. Patients with psychiatric or significant neurological disorders, spinal cord damage, use of any other agents for Meniere's disease.
6. Patients with ear surgery for vestibular disorders.
7. Patients with peptic ulcer (including a history of this disorder).
8. Patient has a history of immunodeficiency disease.
9. Patient has a history of previous endolymphatic sac surgery.
10. Patient has a history of previous use of intratympanic (IT) gentamicin in the affected ear.
11. History of tympanostomy tubes with evidence of perforation or lack of closure.
12. Patient has experienced an adverse reaction to IT injection of steroids.
13. Patient has used an investigational drug or device in 3 months prior to screening.
14. Patients with hypersensitivity to the active substance or to any of the excipients of the study drug.
15. Patients with pheochromocytoma.
16. Patients with asthmatic bronchitis, bronchial asthma, urticaria, exanthema or allergic rhinitis.
17. Patients with pronounced hypotension.
18. Patients under treatment with MAO inhibitors (including MAO-B selective).
19. 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.
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of significant responders defined as those patients who present a maximum increase of 1 point in two of the intensity, duration or frequency of vertigo attacks score based on GISFaV scale against baseline score registered during patient inclusion.
2. GISFaV self-rating scale involving each item separately for determination of the disturbance stage of vertigo using values of intensity (V: 4-point scale), duration (D: A 5-point scale) and associated symptoms (N: A 3-point scale), frequency of crisis (F: A 5-point scale), quality of life (Q: A 3-point scale) scored respectively.

Secondary endpoints 10

1. Number of asymptomatic days (no vertigo attacks) during treatment period.
2. Patient rates with all the GISFaV items equal to 0 at 3 months.
3. Change in number of monthly vertigo attacks during treatment period.
4. Data of rescue medications used during treatment period
5. 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 registered during patient inclusion in the subgroups of naive patients or pretreated patient with betahistine IR <48 mg/day
6. The Dizziness Handicap Inventory (DHI) rating scale for the identification of the difficulties that patients encounter during the vertiginous disease.
7. 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'.
8. Tinnitus will be scored as: 'none', 'mild', 'moderate' or 'severe'.
9. Pressure sensation will be scored as 'none', 'mild', 'moderate' or 'severe'.
10. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intas Pharmaceuticals Limited

Sponsor organisation

Intas Pharmaceuticals Limited

Address

Corporate House Near Sola Bridge, S G Highway S G Highway

City

Ahmedabad

Postcode

380054

Country

India

Scientific contact point

Organisation

Intas Pharmaceuticals Limited

Contact name

Alba Figuera

Public contact point

Organisation

Intas Pharmaceuticals Limited

Contact name

Alba Figuera

Third parties 3

Sponsor responsibilities

Article 77 compliance

Intas Pharmaceuticals Limited

Article 77 implementation

Intas Pharmaceuticals Limited

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications