A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study of OTO-104 Given as a Single Intratympanic Injection in Subjects with Unilateral Meniere's Disease
This is a Phase 2B study that is Double-blind, Pacebo Controlled. it is designed for study of intratympanic membrane injection in patients with unilateral Meniere's disease. 1 injection of dexamethasone that is suspended in gel form will be given to qualifying subjects. each subject will be followed for a period of 5 months with physical, otologic and audiometric evaluations.
During screening (Visit 1), all subjects will be assessed for eligibility based on the presence of all inclusion criteria (with the exception of #4 and #13) and absence of all exclusion criteria (with the execption of #14) and will enter into a 4-week lead-in period. During the lead-in period, subjects will record their daily vertigo experience via an iVRS (interactive Voice Response System) or iWRS (interactive Web Response System) daily diary to allow for a baseline assessment of these events. a definitive vertigo episode is defined as an episode lasting at least 20 minutes and corresponds to a Vertigo Score of 2 or more. if multiple attacks occur on the same day, only the worst attack should be scored. Following the lead-in period, eligible subjects based on inclusion criteria #4 and #13 and exclusion criteria #1, #14 and #15 will be randomized to 12 mg oTo-104 or placebo using a 1:1 allocation ratio such that 70 subjects will receive 12 mg oTo-104 and 70 subjects will receive placebo.
after a single intratympanic injection with study drug on Day 1, subjects will enter a 16-week follow-up period during which subjects will continue to record their daily vertigo experience via the iVRS or iWRS daily diary. Subjects will visit the study site at Weeks 4, 8 and 12 during the follow-up period for additional efficacy and safety assessments. efficacy and safety assessments will also be completed at the end of the study (Week 16) or upon early withdrawal from the study.
To be eligible for this study at Screening (Visit 1), presence of all inclusion criteria (with the exception of #4 and #13) must be satisfied with a
* answer (unless not applicable). At Baseline/Treatment (Visit 2), inclusion criteria #4 and #13 must be satisfied with a
* answer (unless not applicable):
1. Subject is a male or female aged 18 to 85 years, inclusive.
2. Subject has a diagnosis of definite unilateral Meniere[Single Quote]s disease by 1995 AAO-HNS criteria.
3. Subject self-reports at least 2 definitive episodes of vertigo per month for the 2 months prior to the study lead-in period.
4. Subject has experienced and recorded at least 2 definitive vertigo episodes during the 4- week lead-in period.
5. Subject has documented asymmetric sensorineural hearing loss according to AAO-HNS 1995 criteria, and is defined as either 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, or the PTA at 500, 1000, 2000 and 3000 Hz is 20 dB or more poorer in the ear in question than on the opposite side.
6. Subject agrees to maintain their current treatments for Meniere[Single Quote]s disease while on-study.
7. Subjects currently on a low-salt diet and/or diuretic at the time of screening agree to continue this treatment throughout the study.
8. Female subjects of childbearing potential (i.e., not surgically sterile and/or not post- menopausal (>=6 months since last menstrual period and 45 years of age or older)) must have a negative pregnancy test before randomization. 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 adequate contraceptive precautions for the duration of the study (e.g., oral contraceptives, contraceptive implant or injection, intrauterine device, condom and spermicide, or diaphragm and spermicide).
9. Subject is willing to comply with the protocol and attend all study visits.
10. Subject is able to use the telephone.
11. Subject is able to provide written informed consent, including agreement to country specific privacy language either within the informed consent or in ancillary documents compliant with Health Insurance Portability and Accountability Act (HIPAA) in the US, and Personal Information Protection and Electronic Documents Act (PIPEDA) in Canada, before the initiation of any study-related procedures.
12. Subject completed at least 22 of 28 diary entries during screening.