Hearing Loss
Conditions
Brief summary
The aim of this study is to detect the presence of SENS-401 in the perilymph of participants undergoing cochlear implant surgery after 7 days of oral administration of SENS-401.
Detailed description
The study is a Phase IIa, open-label, randomized and controlled study investigating repeated twice-daily administration of oral SENS-401 in adult participants with moderately severe to profound hearing loss who have already agreed to undergo cochlear implant surgery justified by their hearing impairment. After written informed consent is obtained and screening procedures completed, 27 eligible participants will be randomized on Day 1 to either Arm A or Arm B in ratio 2:1 (18 participants in Arm A and 9 participants in Arm B). Arm A participants will commence dosing with twice-daily oral 43.5 mg SENS-401 for 7 days prior to their scheduled cochlear implant surgery on Day 8 and up to 42 days from day of surgery inclusive. Arm B participants will not receive any treatment other than their scheduled cochlear implant surgery.
Interventions
Patients will receive SENS-401 ((R)-azasetron besylate) for 7 days B.I.D. before cochlear implant surgery and during 6 weeks after the surgery.
Sponsors
Sensorion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: Potential participants must fulfil all of the following main inclusion criteria to be eligible for the study: 1. Adults aged from 18 years and older; 2. Meets the locally approved indication for cochlear implantation. The individual must have freely consented to the cochlear implant surgery before being offered to participate in the SENS-401-203 study; 3. Signed and dated written informed consent; Main
Exclusion criteria
Individuals will be excluded from the study if any of the following main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With SENS-401 Detected in Perilymph | Day 8 | A sample of perilymph was obtained from the round window during the cochlear implant surgery from Arm A participants only, after seven days of SENS-401. The percentage of participants with levels of SENS-401 in the perilymph above the Limit of Quantification was then calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SENS-401 Perilymph Concentration | Day 8 | SENS-401 perilymph concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only). |
| SENS-401 Plasma Concentration | Day 8 | SENS-401 plasma concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only). |
| Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 49 and Day 105 | Pure tone audiometry (PTA) in decibels (dB) is a behavioral, subjective hearing test used to assess an individual's hearing threshold levels and determine the degree of hearing loss. A decrease of hearing threshold is considered as an improvement and an increase as a deterioration of the audition. PTA assessments were conducted on Day 1 after randomization (prior to the first dose of the study drug for Arm A), at the Day 49 visit, and at the end of the study (EOS) on Day 105 for all participants (Arms A and B). The change in hearing threshold from baseline in the implanted ear was evaluated at 500 Hz and as an average across three frequencies (250, 500, and 750 Hz) using PTA. |
Countries
Australia, France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A, Treatment Arm Arm A: Participants scheduled for cochlear implantation and treated with oral 43.5 mg SENS-401 (R-Azasetron Besylate) twice daily for up to 49 days.
SENS-401 (R-Azasetron Besylate): Patients will receive SENS-401 ((R)-azasetron besylate) for 7 days B.I.D. before cochlear implant surgery and during 6 weeks after the surgery. | 17 |
| B, Control Arm Arm B: Participants scheduled for cochlear implants and not treated with SENS-401 (R-Azasetron Besylate). | 10 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Screen Failure | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | A, Treatment Arm | B, Control Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 4 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 6 Participants | 16 Participants |
| Age, Continuous | 61.67 years STANDARD_DEVIATION 13.602 | 61.52 years STANDARD_DEVIATION 14.968 | 61.61 years STANDARD_DEVIATION 13.835 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Australia | 5 participants | 4 participants | 9 participants |
| Region of Enrollment France | 12 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 10 |
| other Total, other adverse events | 13 / 17 | 1 / 10 |
| serious Total, serious adverse events | 2 / 17 | 0 / 10 |
Outcome results
Primary
Proportion of Participants With SENS-401 Detected in Perilymph
A sample of perilymph was obtained from the round window during the cochlear implant surgery from Arm A participants only, after seven days of SENS-401. The percentage of participants with levels of SENS-401 in the perilymph above the Limit of Quantification was then calculated.
Time frame: Day 8
Population: The pharmacokinetic (PK) Set included all participants who received at least one dose of SENS-401 (16). Note that one (1) participant treated with SENS-401 did not have a perilymph sample collected during cochlear implant surgery so the overall number of participants analyzed for this outcome is 15.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A, Treatment Arm | Proportion of Participants With SENS-401 Detected in Perilymph | 15 Participants |
| B, Control Arm | Proportion of Participants With SENS-401 Detected in Perilymph | 0 Participants |
Secondary
Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies
Pure tone audiometry (PTA) in decibels (dB) is a behavioral, subjective hearing test used to assess an individual's hearing threshold levels and determine the degree of hearing loss. A decrease of hearing threshold is considered as an improvement and an increase as a deterioration of the audition. PTA assessments were conducted on Day 1 after randomization (prior to the first dose of the study drug for Arm A), at the Day 49 visit, and at the end of the study (EOS) on Day 105 for all participants (Arms A and B). The change in hearing threshold from baseline in the implanted ear was evaluated at 500 Hz and as an average across three frequencies (250, 500, and 750 Hz) using PTA.
Time frame: Day 49 and Day 105
Population: Efficacy Set included all participants who have at least hearing threshold parameter data at Baseline and Day 49
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| A, Treatment Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 49 : LS Mean change from baseline at 500Hz | 19.7 dB |
| A, Treatment Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 49 : LS Mean change from baseline at 250-750 Hz | 16.25 dB |
| A, Treatment Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 105: LS Mean change from baseline at 500 Hz | 25.6 dB |
| A, Treatment Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 105: LS Mean change from baseline at 250-750 Hz | 20.97 dB |
| B, Control Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 105: LS Mean change from baseline at 250-750 Hz | 34.82 dB |
| B, Control Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 49 : LS Mean change from baseline at 500Hz | 30.6 dB |
| B, Control Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 105: LS Mean change from baseline at 500 Hz | 34.5 dB |
| B, Control Arm | Change of Hearing Threshold From Baseline in the Implanted Ear at Several Frequencies | Day 49 : LS Mean change from baseline at 250-750 Hz | 30.65 dB |
p-value: 0.140695% CI: [-25.9, 3.9]ANCOVA
p-value: 0.056795% CI: [-29.24, 0.45]ANCOVA
p-value: 0.258895% CI: [-25, 7.1]ANCOVA
p-value: 0.097995% CI: [-30.49, 2.8]ANCOVA
Secondary
SENS-401 Perilymph Concentration
SENS-401 perilymph concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only).
Time frame: Day 8
Population: The pharmacokinetic (PK) Set included all participants who received at least one dose of SENS-401 (16). Note that one (1) participant treated with SENS-401 did not have a perilymph sample collected during cochlear implant surgery so the overall number of participants analyzed for this outcome is 15.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A, Treatment Arm | SENS-401 Perilymph Concentration | 45.8009 ng/ml | Standard Deviation 45.47158 |
Secondary
SENS-401 Plasma Concentration
SENS-401 plasma concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only).
Time frame: Day 8
Population: The pharmacokinetic (PK) Set included all participants who received at least one dose of SENS-401 (16).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A, Treatment Arm | SENS-401 Plasma Concentration | 59.6244 ng/ml | Standard Deviation 27.98319 |