Efficacy of SENS-111 in Patients Suffering From Acute Unilateral Vestibulopathy

• SENS-111 100mg (Drug): SENS-111 100mg is presented as 1 Oral Dispersible Tablet of SENS-111 100mg + 1 Oral Dispersible Tablet of placebo given twice on Day 1, second intake given approximately 12 hours (9 to 15 hours) after the first intake and thereafter given once daily on Days 2 to 5 inclusive. The corresponding total dose will be 500 mg for the entire study.
• SENS-111 200mg (Drug): SENS-111 200mg is presented as 2 Oral Dispersible Tablet of SENS-111 100mg given twice on Day 1,second intake given approximately 12 hours (9 to 15 hours) after the first intake and thereafter given once daily on Days 2 to 5 inclusive. The corresponding total dose will be 1000 mg for the entire study.
• Placebo Oral Tablet (Drug): Placebo is presented as 2 Oral Dispersible Tablets of placebo given twice on Day 1, second intake given approximately 12 hours (9 to 15 hours) after the first intake and thereafter given once daily on Days 2 to 5 inclusive. The corresponding total dose will be 0 mg for the entire study.

Primary outcomes

• Standing Vertigo Intensity [over the 4 treatment days]: The primary efficacy endpoint was the Area Under Curve (AUC) for the vertigo intensity measured by the Vertigo Intensity Visual Analogue Scale (VI-VAS) in standing position over the 4 treatment days (8 post-baseline assessments). The vertigo Intensity VAS is a non-anchored 10cm horizontal line. Patients were asked to rate the intensity of their vertigo making a vertical mark crossing the horizontal 10 cm line to indicate the severity from 0-100 when 0 indicates no severity and 100 indicates worse severity.

Secondary outcomes

• Worst Spontaneous Vertigo Intensity [over the 4 treatment days]: Worst spontaneous vertigo intensity measured by the AUC of the worst Vertigo Intensity Visual Analogue Scale (VI-VAS) over the 4 treatment days (8 post-baseline assessments). The vertigo Intensity VAS is a non-anchored 10cm horizontal line. Patients were asked to rate the intensity of their vertigo making a vertical mark crossing the horizontal 10 cm line to indicate the severity from 0-100 when 0 indicates no severity and 100 indicates worse severity
• Proprioception D5 [End of treatment Day 5]: The Romberg test assess the patient's ability to stand unassisted under 6 successive test conditions of increasing difficulty. In this test higher values are indicating a higher ability to stand unassisted, minimum total score is : 0 (impossibility to stand unassisted in any of the six conditions) and maximum is: 6. The change from Baseline of the total score of the six conditions of the Romberg test at the end of treatment (EOT) (Day 5) is evaluated.
• Proprioception D28 [End of study Day 28]: The Romberg test assess the patient's ability to stand unassisted under 6 successive test conditions of increasing difficulty. In this test higher values are indicating a higher ability to stand unassisted, minimum total score is : 0 (impossibility to stand unassisted in any of the six conditions) and maximum is: 6. Change from Baseline of the total score of the six conditions of the Romberg test at the end of study (EOS) (Day 28) is evaluated.
• Vestibular Spontaneous Nystagmus D5 [End of treatment Day 5 compared to basleine]: Change from Baseline of the Peak Slow Phase Velocity of the Peripheral Vestibular Spontaneous Nystagmus at the end of treatment (EOT) (Day 5). It is intended to record eye movements resulting from Nystagmus, measured by Oculography performed in complete darkness with visual fixation (10 seconds) or without fixation (30 seconds).
• Vestibular Spontaneous Nystagmus D28 [28 days compared to baseline]: Change from Baseline of the Peak Slow Phase Velocity of the Peripheral Vestibular Spontaneous Nystagmus at End of Study (Day 28). It is intended to record eye movements resulting from Nystagmus, measured by Oculography performed in complete darkness with visual fixation (10 seconds) or without fixation (30 seconds).
• Nausea Severity [over the 4 Treatment Days (Day 5)]: Nausea Severity measured by the Area under the Curve of the Nausea Intensity Visual Analogue Scale (NI-VAS). Patients were asked to rate the intensity of their nausea making a vertical mark crossing the horizontal 10 cm line to indicate the severity from 0-100 when 0 indicates no severity and 100 indicates worse severity.

Sex: All, ages: 18 Years to 75 Years

Inclusion criteria includes, but is not limited to:

* Subject has a diagnosis of definite Acute Unilateral Vestibulopathy

Exclusion criteria includes, but is not limited to:

* Acute continuous vertigo lasting more than 72 hours prior to randomization
* History of acute or chronic vestibular diseases
* History of prior acute central vestibular lesion
* Acute or chronic disease of middle ear

Participant flow

Outcome results

• Standing Vertigo Intensity (Primary), Mean, mm*day: SENS-111 100mg 165.10 +/- 71.02; SENS-111 200mg 155.10 +/- 83.06; Placebo 136.60 +/- 62.61 (p 0.8466)
• Worst Spontaneous Vertigo Intensity (Secondary), Mean, mm*day: SENS-111 100mg 180.10 +/- 67.20; SENS-111 200mg 170.40 +/- 89.83; Placebo 140.8 +/- 64.66 (p 0.9538)
• Proprioception D5 (Secondary), Mean, score on a scale: SENS-111 100mg 2.10 +/- 1.46; SENS-111 200mg 2.00 +/- 1.79; Placebo 2.40 +/- 1.45 (p 0.3166)
• Proprioception D28 (Secondary), Mean, score on a scale: SENS-111 100mg 2.70 +/- 1.60; SENS-111 200mg 3.00 +/- 1.64; Placebo 3.20 +/- 1.46 (p 0.393)
• Vestibular Spontaneous Nystagmus D5 (Secondary), Mean, degrees per second: SENS-111 100mg -2.30 +/- 11.64; SENS-111 200mg -3.50 +/- 10.27; Placebo -5.7 +/- 8.15
• Vestibular Spontaneous Nystagmus D28 (Secondary), Mean, degrees per second: SENS-111 100mg -4.80 +/- 15.10; SENS-111 200mg -7.9 +/- 12.76; Placebo -7.7 +/- 11.59
• Nausea Severity (Secondary), Mean, mm*day: SENS-111 100mg 93.00 +/- 78.39; SENS-111 200mg 91.50 +/- 79.73; Placebo 92.60 +/- 57.28 (p 0.5324)

Adverse events

Time frame: up to end of study 28 days

Serious adverse events by term

Other adverse events by term

• Statistical Analysis Plan (PDF, 2019-11-12)
• Study Protocol (PDF, 2017-02-09)

• Michael STRUPP, MD, Principal investigator, University Hospital Munich