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 |
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. |
|
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 |
|
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 confirm the efficacy of OTO-104 in subjects with Meniere’s disease, as measured by the number of definitive vertigo days (DVD) at Week 12 (the 4-week interval from Week 9 through Week 12). |
|
E.2.2 | Secondary objectives of the trial |
To describe the safety profile of OTO-104 in subjects with Meniere’s disease. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject is a male or female aged 18 to 85 years, inclusive.
- Subject has a diagnosis of definite unilateral Meniere’s disease by 1995 AAO-HNS criteria.
- Subject self-reports active, definitive vertigo episodes for the 2 months prior to the study lead-in period.
- Subject has documented asymmetric sensorineural hearing loss at screening or within the past 12 months according to AAO-HNS 1995 criteria defined as one of the following:
a. The arithmetic mean of hearing thresholds (pure tone average, PTA) at 250, 500 and 1000 Hz of 15 dB or more higher than the PTA of 1000, 2000, and 3000 Hz,
b. The arithmetic mean of PTA at 500, 1000, 2000 and 3000 Hz is 20 dB or more poorer in the ear in question than on the opposite side,
c. It is the judgment of the investigator that the subject’s hearing loss meets reasonable audiometric criteria for hearing loss characteristic of Meniere’s disease, and if so, it should be justified and documented.
- Subject is able to use the telephone to complete their daily diary.
At the completion of the first 28 days of the lead-in period:
- Subject completed at least 22 of 28 diary entries during the 4-week lead-in period. |
|
E.4 | Principal exclusion criteria |
- Subject has an infection in the ear, sinuses, or upper respiratory system at the time of randomization.
- Subject is pregnant or lactating.
- Subject has a history of immunodeficiency disease.
- 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 monomeric tympanic membrane.
- Subject has used systemic steroids within 1 month prior to entering the lead-in period.
- Subject has a hypersensitivity to dexamethasone or any of the excipients in OTO-104
- Subject has previously been randomized to a trial of OTO-104. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of definitive vertigo days (DVD) at Week 12 [the 4-week (28-day) interval from Week 9 through Week 12] |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- The number of definitive vertigo days (DVD) at Week 8 [the 4-week (28-day) interval from Week 5 through Week 8]
- The number of definitive vertigo days (DVD) at Week 4 [the 4-week (28-day) interval from Week 1 through Week 4]
- The change from baseline in vertigo frequency (VF) during the 4-week study interval (Week 9 through Week 12), where vertigo frequency is defined as the proportion of days during the 4-week interval where a definitive vertigo episode was recorded divided by the number of non-missing diary entries for the relevant interval
The change from baseline with respect to severity of vertigo episodes as measured by the mean Vertigo Score during the 4-week study interval (Week 9 through Week 12)
- The change from baseline in average daily count of vertigo episodes, during the 4-week study interval (Week 9 through Week 12)
- Occurrence of Normal activity, Slight limitation, Moderate limitation, Sick at home, and Bed ridden events as a consequence of vertigo at Week 12
- SF-36 at Week 12
o Physical Health Summary Measure
o Mental Health Summary Measure
o 8 Scales |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 4, Week 8, Week 12 as specified in the endpoint description. |
|
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
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
|
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |