Treatment of acute peripheral vertigo MedDRA version: 20.0 Level: LLT Classification code 10059614 Term: Vestibular vertigo System Organ Class: 100000004854
Conditions
Interventions
Product Name: betahistine dihydrochloride
Product Code: AM-125
Pharmaceutical Form: Nasal spray, solution
INN or Proposed INN: Betahistine dihydrochloride
CAS Number: 5579-84-0
Current Sponsor code: A
2-(2-(Methylamino)ethyl)pyridine dihydrochloride
N-methyl-N-(2-pyridin-2-ylethyl)amine dihydrochloride
Methyl(2-[2- pyridyl]ethyl)amine
N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Nasal spray
N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 16-
Product Name: betahistine dihydrochloride
Product Code: AM-
N-methyl-2-(pyridin-2-yl)ethanamine dihydrochloride
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Nasal spra
Sponsors
Auris Medical AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects have to meet all of the following inclusion criteria to be eligible for enrolment into the study: 1. Scheduled for neurosurgery (vestibular schwannoma resection, labyrinthectomy or vestibular neurectomy) 2. Small to moderately large vestibular schwannoma (Koos grade I-III; Samii grade T1-T3b; = 30 mm in diameter in cerebellopontine angle) that does not displace the brainstem, documented by magnetic resonance imaging not older than six months. or Indication for labyrinthectomy or vestibular neurectomy. 3. Confirmed vestibular function on both sides (> 6 deg/sec sum of bithermal max. slow phase velocity on the affected side in caloric video/electronystagmography (VNG/ENG) and > 10 deg/sec sum of bithermal max. slow phase velocity on the contralateral side). 4. Presence of symptoms of acute peripheral vertigo: • Subjective symptoms of vertigo (rating of at least “two” in EEV questionnaire question 1: illusion of movement) • Spontaneous nystagmus beating towards the contralateral side. SVV deviation > 2.5°from the true vertical. 5. Age at SV (screening visit) =18 years and =70 years. 6. Negative urine pregnancy test for women of childbearing potential. 7. Willing and able to attend the study visits. 8. Able to read and understand study documents, to complete the relevant questionnaires and rating scales and follow Investigator instructions. 9. Signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Prior radiotherapy (gamma knife, intensity modulated radiation therapy) irradiating the brain-stem with more than 4 Gy. 2. Any ongoing other peripheral vestibular disorder (e.g. Meniere’s disease, benign paroxysmal vertigo, vestibular neuritis) or central vestibular disorder (e.g. vestibular migraine, central vertigo). 3. Vestibular rehabilitation therapy or presurgical gentamicin therapy (i.e. “pre-habilitation therapy”) within the past three months prior to neurosurgery. 4. Any clinically relevant nasal obstruction or pathology precluding effective and/or safe intranasal delivery. 5. Diagnosis of phaeochromocytoma. 6. Ongoing upper respiratory tract infection or allergic rhinitis (symptomatic). 7. Any treatment with antihistamines, anti-emetics or benzodiazepines that is ongoing or planned during the IMP treatment period. 8. Any history of clinically relevant drug hypersensitivity, urticaria, or other severe allergic diathesis as well as current moderate or severe allergic disorders or hay fever. 9. Subjects with diagnosed anxiety disorders, depression, schizophrenia or other significant psychiatric diseases requiring current drug treatment or subjects who required treatment in the previous three months prior to enrolment for any of these diseases. 10. Any clinically relevant respiratory, cardiovascular, neurological disorder (e.g. neurofibromatosis type 2, except vertigo), relevant orthopaedic or visual limitation, relevant abnormality in laboratory test or physical examination or other abnormality that in the opinion of the Investigator or Sponsor may pose a safety risk to a subject in this study, which may confound efficacy or safety assessment, or may interfere with study participation. 11. Any clinically relevant complication during or after neurosurgery that in the opinion of the Investigator or Sponsor may pose a safety risk to a subject in this study, which may confound efficacy or safety assessment, or may interfere with study participation. 12. Known hypersensitivity, allergy or intolerance to the study medication or any history of severe, abnormal drug reaction. 13. History within the past two years or presence of drug abuse or alcoholism. 14. Women who are breast-feeding, pregnant or who are planning to become pregnant during the study. 15. Women of childbearing potential who are unwilling or unable to use an effective method of avoiding pregnancy from the SV until the end of the study. Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of less than 1 used consistently and correctly (including implantable, injectable, oral and transdermal contraceptives, intrauterine devices, or a sterile sexual partner, or being abstinent). 16. Concurrent treatment with another investigational medicinal product or prior treatment with another investigational medicinal product within 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of Part A is a. to explore and provide an estimate of the dose response curve for AM-125, and b. to evaluate the efficacy of AM-125 compared to placebo in reducing the symptoms of vestibular dysfunction and accelerating vestibular compensation following neurosurgery. The primary objective of Part B is to evaluate the efficacy of two selected doses of AM-125 versus placebo, as determined based on the results from Part A, in reducing the symptoms of vestibular dysfunction and accelerating vestibular compensation following neurosurgery compared to placebo. ;Secondary Objective: The secondary objective of Part A is to compare the treatment effect of oral betahistine (open label) versus AM-125 in reducing the symptoms of vestibular dysfunction and accelerating vestibular compensation following neurosurgery. The secondary objective of both Part A and Part B is to describe the safety and tolerability of AM-125 in the treatment of acute peripheral vertigo following neurosurgery. ;Primary end point(s): Primary efficacy endpoint Improvement in tandem Romberg test (eyes closed) from TV (baseline) to FUV4. Primary safety endpoint for Part A and B: Frequency of occurrence of moderate-severe nasal symptoms at TV or any FUV and overall.;Timepoint(s) of evaluation of this end point: End of Part A for primary efficacy endpoints of Part A. End of Part B for primary efficacy endpoints of Part B. End of Part A and Part B for primary safety endpoint of Part A and B. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoint Improvement of time standing on foam (eyes closed) from TV (baseline) to FUV2. Secondary efficacy endpoints: • Improvement of time standing on foam (eyes closed) from TV (baseline) to FUV1, FUV3 and FUV4; • Improvement in tandem Romberg test (eyes closed) from TV (baseline) to FUV1, FUV2 and FUV3; • Improvement in tandem gait from TV (baseline) to all FUVs; • Improvement of subjective visual vertical deviation from TV (baseline) to all FUVs • Change in the frequency of horizontal spontaneous nystagmus from TV (baseline) to all FUVs. Secondary safety endpoints: • Frequency of occurrence of any nasal symptoms at TV or any FUV and overall; • Occurrence of adverse events after intranasal administration; • Occurrence of adverse events after oral administration (part A only).;Timepoint(s) of evaluation of this end point: End of Part A for secondary efficacy endpoints of Part A. End of Part B for secondary efficacy endpoints of Part B. End of Part A and/or Part B for secondary safety endpoints of Part A and B. | — |
Countries
Australia, Belgium, Canada, Czechia, Czech Republic, France, Germany, Italy, Poland, Slovakia, United Kingdom
Contacts
Public ContactDirector Translational Research
Auris Medical AG
Outcome results
None listed