ClinicalTrials.gov
ClinicalTrials.gov Menu

AM-101 in the Treatment of Post-Acute Tinnitus 1 (AMPACT1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01934010
Recruitment Status : Completed
First Posted : September 4, 2013
Results First Posted : March 9, 2018
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
Auris Medical, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Tinnitus
Intervention Drug: AM-101
Enrollment 260

Recruitment Details A total of 260 subjects were enrolled and 257 subjects were treated in overall 59 active sites in Canada (6), the United States (35), the Czech Republic (7), Israel (2), Turkey (3) and Republic of South Korea (6). Subjects could only participate if they had been previously enrolled and completed the participation in the TACTT2 study.
Pre-assignment Details

Main Inclusion Criteria:

  • completion of TACTT2 study
  • negative pregnancy test (women of childbearing potential)
  • willing and able to attend the study visits during at least one treatment cycle.
Arm/Group Title 1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Hide Arm/Group Description Subjects participated in 1 treatment cycle and received one round of 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0-D4) Subjects that participated in 2 treatment cycles of the AMPACT1 study, received 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0 - D4) in cycle 1 and after final follow-up (D84) of cycle 1, they rolled-over to treatment cycle 2 receiving once more 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D84 - D88). Subjects that participated in all 3 treatment cycles of the AMPACT1 study, received 3 x 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days. The subjects could only roll-over if they completed the final follow-up of the previous cycle and were still eligible. In cycle 1 treatment was within D0 - D4. Cycle 2 treatment within D84 - D88. And treatment for cycle 3 within D168-D172. Final follow-up after 3 treatment cycles was FUV9 (D252).
Period Title: Overall Study
Started 114 67 76
Completed 91 56 74
Not Completed 23 11 2
Reason Not Completed
Adverse Event             1             1             0
Withdrawal by Subject             15             6             2
Lost to Follow-up             7             4             0
Arm/Group Title 1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101 Total
Hide Arm/Group Description Subjects participated in 1 treatment cycle and received one round of 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0-D4) Subjects that participated in 2 treatment cycles of the AMPACT1 study, received 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0 - D4) in cycle 1 and after final follow-up (D84) of cycle 1, they rolled-over to treatment cycle 2 receiving once more 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D84 - D88). Subjects that participated in all 3 treatment cycles of the AMPACT1 study, received 3 x 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days. The subjects could only roll-over if they completed the final follow-up of the previous cycle and were still eligible. In cycle 1 treatment was within D0 - D4. Cycle 2 treatment within D84 - D88. And treatment for cycle 3 within D168-D172. Final follow-up after 3 treatment cycles was FUV9 (D252). Total of all reporting groups
Overall Number of Baseline Participants 114 67 76 257
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 114 participants 67 participants 76 participants 257 participants
<=18 years 0 0 0 0
Between 18 and 65 years 106 61 64 231
>=65 years 8 6 12 26
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 114 participants 67 participants 76 participants 257 participants
43.1  (14.1) 44.7  (13.9) 47.6  (15.5) 44.8  (14.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 114 participants 67 participants 76 participants 257 participants
Female 25 17 21 63
Male 89 50 55 194
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 114 participants 67 participants 76 participants 257 participants
United States 71 45 40 156
Czechia 24 7 22 53
Canada 4 11 9 24
Israel 1 1 1 3
South Korea 11 1 4 16
Turkey 3 2 0 5
1.Primary Outcome
Title Frequency of Subjects With a Deterioration of Hearing Threshold at Day 35 (Air Conduction)
Hide Description

Valid for Safety Analysis Set was used.

Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound.

The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies.

Time Frame Day 1 (TV1) to Day 35 (FUV2) of cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available.
Arm/Group Title 1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Hide Arm/Group Description:
Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV2.
Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV2.
Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV2.
Overall Number of Participants Analyzed 103 67 74
Measure Type: Number
Unit of Measure: Number subject affected
10 2 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Cycle AM-101, 2 Cycles AM-101
Comments Fisher's exact test to assess if there is a difference in deterioration of hearing threshold between subjects that received 1 treatment cycle with AM-101 or others who received 2 treatment cycles.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 Cycle AM-101, 3 Cycles AM-101
Comments Fisher's exact test to assess if there is a difference in deterioration of hearing threshold between subjects that received 1 treatment cycle with AM-101 or others who received 3 treatment cycles.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2 Cycles AM-101, 3 Cycles AM-101
Comments Fisher's exact test to assess if there is a difference in deterioration of hearing threshold between subjects that received 2 treatment cycles with AM-101 or others who received 3 treatment cycles.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Frequency of Subjects With a Deterioration of Hearing Threshold at Day 119 (Air Conduction)
Hide Description

Valid for Safety Analysis Set was used.

Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound.

The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies.

Time Frame Day 84 (TV4) to Day 119 (FUV5) of cycle 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available.

Subjects from Cycle 1 did not participate in Cycle 2 and 3 and are therefore "zero".

Arm/Group Title 2 Cycles AM-101 3 Cycles AM-101
Hide Arm/Group Description:
Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV5.
Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV5.
Overall Number of Participants Analyzed 59 75
Measure Type: Number
Unit of Measure: Number subject affected
1 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2 Cycles AM-101, 3 Cycles AM-101
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4403
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Primary Outcome
Title Frequency of Subjects With a Deterioration of Hearing Threshold at Day 203 (Air Conduction)
Hide Description

Valid for Safety Analysis Set was used.

Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound.

The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies.

Time Frame Day 168 (TV7) up to Day 203 (FUV8) of cycle 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 3 Cycles AM-101
Hide Arm/Group Description:
Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV8.
Overall Number of Participants Analyzed 74
Measure Type: Number
Unit of Measure: Number subject affected
2
4.Secondary Outcome
Title Frequency of Subjects With a Deterioration of Hearing Threshold at Day 84 (Air Conduction)
Hide Description

Valid for Safety Analysis Set was used.

Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound.

The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies.

Time Frame Day 1 (TV1) to Day 84 (FUV3) of cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available.
Arm/Group Title 1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Hide Arm/Group Description:
Subjects that participated only in 1 treatment cycle. This endpoint counts existing deteriorations at FUV3.
Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV3.
Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV3.
Overall Number of Participants Analyzed 91 66 75
Measure Type: Number
Unit of Measure: Number subject affected
10 3 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Cycle AM-101, 2 Cycles AM-101
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2401
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 Cycle AM-101, 3 Cycles AM-101
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2 Cycles AM-101, 3 Cycles AM-101
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Frequency of Subjects With a Deterioration of Hearing Threshold at Day 168 (Air Conduction)
Hide Description

Valid for Safety Analysis Set was used.

Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound.

The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies.

Time Frame Day 84 (TV4) to Day 168 (FUV6) of cycle 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available.
Arm/Group Title 2 Cycles AM-101 3 Cycles AM-101
Hide Arm/Group Description:
Subjects that participated in 2 treatment cycles. This endpoint lists deteriorations at FUV6.
Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV6.
Overall Number of Participants Analyzed 55 76
Measure Type: Number
Unit of Measure: Number subject affected
0 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2 Cycles AM-101, 3 Cycles AM-101
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Frequency of Subjects With a Deterioration of Hearing Threshold at Day 252 (Air Conduction)
Hide Description

Valid for Safety Analysis Set was used.

Air conduction: The atmospheric transmission of sound to the inner ear through the external auditory canal and via structures of the middle ear. The ability of hearing is measured in decibel (dB). The hearing threshold, is the lowest sound pressure where the ear can perceive still a sound.

The endpoint deterioration of hearing threshold ≥15 dB in two contiguous test frequencies means that hearing worsens ≥15 dB in two neighboring sound frequencies.

Time Frame Day 168 (TV7) to Day 252 (FUV9) of cycle 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes all subjects that had at least one intratympanic injection. Subjects are only considered at a time point if the hearing threshold is available.
Arm/Group Title 3 Cycles AM-101
Hide Arm/Group Description:
Subjects that participated in 3 treatment cycles. This endpoint lists deteriorations at FUV9.
Overall Number of Participants Analyzed 74
Measure Type: Number
Unit of Measure: Number subject affected
2
Time Frame From baseline to end of study at all visits, up to Day 252.
Adverse Event Reporting Description Assessed by Investigator at all visits. In non-serious adverse events section, under occurrences (all), reported numbers are "subjects affected".
 
Arm/Group Title 1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Hide Arm/Group Description Subjects participated in 1 treatment cycle and received one round of 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0-D4) Subjects that participated in 2 treatment cycles of the AMPACT1 study, received 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D0 - D4) in cycle 1 and after final follow-up (D84) of cycle 1, they rolled-over to treatment cycle 2 receiving once more 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days (D84 - D88). Subjects that participated in all 3 treatment cycles of the AMPACT1 study, received 3 x 3 repeated doses of AM-101 gel (0.87 mg/mL) within 5 days. The subjects could only roll-over if they completed the final follow-up of the previous cycle and were still eligible. In cycle 1 treatment was within D0 - D4. Cycle 2 treatment within D84 - D88. And treatment for cycle 3 within D168-D172. Final follow-up after 3 treatment cycles was FUV9 (D252).
All-Cause Mortality
1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/114 (1.75%)   1/67 (1.49%)   1/76 (1.32%) 
Investigations       
Liver function test increased  1  1/114 (0.88%)  0/67 (0.00%)  0/76 (0.00%) 
Musculoskeletal and connective tissue disorders       
Osteonecrosis  1  0/114 (0.00%)  0/67 (0.00%)  1/76 (1.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lip and/or oral cavity cancer  1  1/114 (0.88%)  0/67 (0.00%)  0/76 (0.00%) 
Reproductive system and breast disorders       
Adnexa uteri cyst  1  0/114 (0.00%)  1/67 (1.49%)  0/76 (0.00%) 
Adnexa uteri mass  1  0/114 (0.00%)  1/67 (1.49%)  0/76 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
1 Cycle AM-101 2 Cycles AM-101 3 Cycles AM-101
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/114 (21.93%)   25/67 (37.31%)   37/76 (48.68%) 
Ear and labyrinth disorders       
Ear discomfort  1  3/114 (2.63%)  9/67 (13.43%)  7/76 (9.21%) 
Ear pain  1  10/114 (8.77%)  13/67 (19.40%)  8/76 (10.53%) 
Hypoacusis  1  5/114 (4.39%)  4/67 (5.97%)  4/76 (5.26%) 
Otorrhoea  1  1/114 (0.88%)  4/67 (5.97%)  3/76 (3.95%) 
Tinnitus  1  0/114 (0.00%)  2/67 (2.99%)  5/76 (6.58%) 
Tympanic membrane perforation  1  0/114 (0.00%)  0/67 (0.00%)  3/76 (3.95%) 
Vertigo  1  0/114 (0.00%)  2/67 (2.99%)  1/76 (1.32%) 
Eustachian tube dysfunction  1  1/114 (0.88%)  0/67 (0.00%)  2/76 (2.63%) 
Hyperacusis  1  0/114 (0.00%)  0/67 (0.00%)  2/76 (2.63%) 
Infections and infestations       
Influenza  1  0/114 (0.00%)  2/67 (2.99%)  0/76 (0.00%) 
Nasopharyngitis  1  4/114 (3.51%)  2/67 (2.99%)  6/76 (7.89%) 
Bronchitis  1  0/114 (0.00%)  0/67 (0.00%)  2/76 (2.63%) 
Sinusitis  1  0/114 (0.00%)  0/67 (0.00%)  2/76 (2.63%) 
Upper respiratory tract infection  1  0/114 (0.00%)  1/67 (1.49%)  2/76 (2.63%) 
Nervous system disorders       
Headache  1  5/114 (4.39%)  7/67 (10.45%)  9/76 (11.84%) 
Dizziness  1  0/114 (0.00%)  1/67 (1.49%)  2/76 (2.63%) 
Psychiatric disorders       
Anxiety  1  1/114 (0.88%)  1/67 (1.49%)  2/76 (2.63%) 
Surgical and medical procedures       
Artificial crown procedure  1  0/114 (0.00%)  0/67 (0.00%)  2/76 (2.63%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Investigator agrees to submit a copy of any intended communication, presentation or publication (abstract, poster, article, etc.) (all together “Communication”) at least 2 month in advance of the submission of proposed Communication. The Sponsor shall have 60 days, after receipt of said copies, to object to such proposed Communication. In case of such objection, the Investigator shall refrain from making such Communication for 6 months from date of receipt of such objection.
Results Point of Contact
Name/Title: Thomas Meyer, CEO
Organization: Auris Medical Inc.
Phone: +1 312 396 4150
Responsible Party: Auris Medical, Inc.
ClinicalTrials.gov Identifier: NCT01934010     History of Changes
Other Study ID Numbers: AM-101-CL-12-03
First Submitted: August 15, 2013
First Posted: September 4, 2013
Results First Submitted: February 8, 2018
Results First Posted: March 9, 2018
Last Update Posted: May 16, 2018