Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2021-006615-28 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A, Treatment arm | Experimental | 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. |
|
| B, Control arm | No Intervention | Arm B: Participants scheduled for cochlear implantation and not treated with SENS-401 (R-Azasetron Besylate). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SENS-401 (R-Azasetron Besylate) | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| SENS-401 Perilymph Concentration | SENS-401 perilymph concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only). | Day 8 |
| SENS-401 Plasma Concentration | SENS-401 plasma concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only). |
Not provided
Main Inclusion Criteria:
Potential participants must fulfil all of the following main inclusion criteria to be eligible for the study:
Main Exclusion Criteria:
Individuals will be excluded from the study if any of the following main exclusion criteria apply:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Stephen O'Leary, MD | Royal Victoria Eye and Ear Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Victorian Eye and Ear Hospital | Melbourne | Australia | ||||
| Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | B, Control Arm | Arm B: Participants scheduled for cochlear implants and not treated with SENS-401 (R-Azasetron Besylate). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Full Analysis Set (FAS) comprised of all randomized participant. One (1) participant randomized in Arm A was excluded from the FAS due to the failure to satisfy major entry criteria, failure to take at least one dose of SENS-401 and the lack of any data post randomization.
Seventeen (17) participants who received at least one dose of SENS-401 and all 10 participants randomized to no treatment, were included in the FAS.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Count of Participants | Participants | Day 8 |
|
105 days
Adverse events were recorded for all study participants from the time of informed consent to study completion. For arm A other adverse events reported below areTreatment Emergent Adverse Events defined as follow: any untoward medical occurrence reported or observed after treatment administration.
Safety assessments were performed at every site visit for all participants: regular investigator assessment and regular laboratory testing
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular tachycardia | Cardiac disorders | MedDRA (24.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Sensorion | +33 4 67 20 77 30 | contact@sensorion-pharma.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 8, 2023 | Apr 3, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 3, 2024 | Apr 3, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D034381 | Hearing Loss |
| ID | Term |
|---|---|
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000656584 | SENS-401 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Day 8 |
| 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. | Day 49 and Day 105 |
| Bordeaux |
| France |
| Centre Hospitalier Universitaire de Clermont-Ferrand - Hôpital Gabriel Montpied | Clermont-Ferrand | France |
| Centre Hospitalier Universitaire de Lille Hôpital Roger Salengro | Lille | France |
| Hôpital Edouard Herriot | Lyon | France |
| Groupe Hospitalier La Pitié-Salpétrière | Paris | France |
| Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan | Toulouse | France |
| Withdrawal by Subject |
|
| BG001 |
| B, Control Arm |
Arm B: Participants scheduled for cochlear implants and not treated with SENS-401 (R-Azasetron Besylate). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | B, Control Arm | Arm B: Participants scheduled for cochlear implants and not treated with SENS-401 (R-Azasetron Besylate). |
|
|
| Secondary | SENS-401 Perilymph Concentration | SENS-401 perilymph concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only). | 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. | Posted | Mean | Standard Deviation | ng/ml | Day 8 |
|
|
|
| Secondary | SENS-401 Plasma Concentration | SENS-401 plasma concentration on day of cochlear implant surgery after seven days of SENS-401 (arm A only). | The pharmacokinetic (PK) Set included all participants who received at least one dose of SENS-401 (16). | Posted | Mean | Standard Deviation | ng/ml | Day 8 |
|
|
|
| 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. | Efficacy Set included all participants who have at least hearing threshold parameter data at Baseline and Day 49 | Posted | Least Squares Mean | 95% Confidence Interval | dB | Day 49 and Day 105 |
|
|
|
|
| 0 |
| 17 |
| 2 |
| 17 |
| 13 |
| 17 |
| EG001 | B, Control Arm | Arm B: Participants scheduled for cochlear implants and not treated with SENS-401 (R-Azasetron Besylate). | 0 | 10 | 0 | 10 | 1 | 10 |
| Vertigo | Ear and labyrinth disorders | MedDRA (24.1) | Systematic Assessment |
|
| Ear procedural complication | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Infrequent bowel movements | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (24.1) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (24.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (24.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
The PI must in advance inform and provide to the sponsor a copy of the proposed publication. The sponsor may request that the PI remove confidential information from the publication.
| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Day 49 : LS Mean change from baseline at 250-750 Hz |
|
|
| Day 105: LS Mean change from baseline at 500 Hz |
|
|
| Day 105: LS Mean change from baseline at 250-750 Hz |
|
|
| ANCOVA | 0.0567 | An ANCOVA model was used to assess changes from baseline at the average across three frequencies (250-750 Hz) at the Day 49 visit comparing the treatment groups. The treatment group was included as a fixed factor, with baseline values as a covariate. | LS Mean difference Arm A - Arm B | -14.40 | 2-Sided | 95 | -29.24 | 0.45 | The change in hearing threshold from baseline was expected to be smaller in the treated group (arm A) than in the control group (arm B). | Superiority |
| ANCOVA | 0.2588 | An ANCOVA model was used to assess changes from baseline at 500Hz at EOS on Day 105 comparing the treatment groups.The treatment group was included as a fixed factor, with baseline values as a covariate. | LS Mean difference Arm A - Arm B | -9.0 | 2-Sided | 95 | -25.0 | 7.1 | The change in hearing threshold from baseline was expected to be smaller in the treated group (arm A) than in the control group (arm B). | Superiority |
| ANCOVA | 0.0979 | An ANCOVA model was used to assess changes from baseline at the average across three frequencies (250-750 Hz) at EOS on Day 105, comparing the treatment groups. The treatment group was included as a fixed factor, with baseline values as a covariate. | LS Mean difference Arm A - Arm B | -13.84 | 2-Sided | 95 | -30.49 | 2.80 | The change in hearing threshold from baseline was expected to be smaller in the treated group (arm A) than in the control group (arm B). | Superiority |