E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Meniere's disease is an inner ear disease. The symptoms are vertigo (room spinning), tinnitus (ringing in the ears or a feeling of fullness in the ears), and hearing loss. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027183 |
E.1.2 | Term | Meniere's disease |
E.1.2 | System Organ Class | 10013993 - Ear and labyrinth disorders |
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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 |
The objective is to assess the safety of repeat intratympanic injections of 12 mg OTO-104 at 3-month intervals in an open-label study in subjects with unilateral Meniere’s disease. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is a male or female aged 18 years or older.
2. Subject has completed the Phase 2 (104-201403) or Phase 3 (104-201508) clinical study.
3. Female subjects of childbearing potential [i.e., not surgically sterile and/or not post-menopausal (12 months since last menstrual period and 45 years of age or older)] must have a negative urine pregnancy test before enrollment. Women of childbearing potential who are not abstinent from sex with male partners may be entered into the study if they are using and willing to continue to use highly effective or "double barrier" contraceptive precautions for the duration of the study (e.g., oral contraceptives, contraceptive implant or injection, intrauterine device, or "double barrier" methods including condom with diaphragm, male condom with cervical cap, male condom with spermicide, or diaphragm and spermicide).
4. Subject is willing to comply with the protocol and attend all study visits.
5. Subject is able to provide written informed consent, including agreement to local privacy language requirements either within the informed consent or in ancillary documents compliant with local privacy laws before the initiation of any study-related procedures. |
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E.4 | Principal exclusion criteria |
1. Subject has an infection in the ear, sinuses, or upper respiratory system.
2. Subject is pregnant or lactating.
3. Subject has a history of immunodeficiency disease.
4. Subject has active or recent (<1 month prior to screening) middle ear disease, including but not limited to: chronic otitis media, acute otitis media, middle ear effusions, middle ear atelectasis, or cholesteatoma.
5. Subject has an abnormality of the tympanic membrane in the affected ear that would increase the risk associated with intratympanic injection including but not limited to a monomeric, atelectatic or atrophic tympanic membrane.
6. Subject has a history of tympanostomy tubes that includes evidence of perforation or lack of closure.
7. Subject has a history of previous endolymphatic sac surgery.
8. Subject has a history of previous use of intratympanic gentamicin in the affected ear.
9. Subject has history of drop attacks.
10. Subject has used systemic steroids within 1 month prior to Visit 1.
11. Subject has had intratympanic steroids within 1 month prior to Visit 1.
12. Subject has experienced an adverse reaction to intratympanic injection of steroids.
13. Subject has a hypersensitivity to dexamethasone or any of the excipients in OTO-104.
14. Subject has any other clinically significant illness or medical condition that, in the investigator's and the medical monitor's opinion, would prohibit the subject from participating in the study.
15. Subject has participated in a clinical trial within 30 days of Visit 1, not including the OTO-104 Phase 3 study (104-201508). |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Adverse events
- Audiometry assessments
- Tympanometry
- Local tolerability (otoscopic examinations)
- suicide ideation assessment
- Vital signs measurements
- Concomitant medications |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Adverse events - continuous from first injection.
The following are captured at Day 1, Month 3, Month 6
Audiometry assessments
- Tympanometry
- Local tolerability (otoscopic examinations)
- suicide ideation assessment
- Vital signs measurements
- Concomitant medication |
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E.5.2 | Secondary end point(s) |
Global vertigo, tinnitus, subjective hearing and aural fullness change questions |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |