Clinical Trial Results:
A Pilot Study of the Efficacy, Safety, and Tolerability of AX-8 for the Treatment of Refractory Chronic Cough
Summary
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EudraCT number |
2017-003108-27 |
Trial protocol |
GB |
Global end of trial date |
11 Jun 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Jun 2019
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First version publication date |
27 Jun 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AX8-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Axalbion SA
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Sponsor organisation address |
EPFL-Innovation Park, Bâtiment C, Lausanne, Switzerland, CH-1015
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Public contact |
Olivier Poirot, Axalbion SA, +41 76 341 81 38, opoirot@axalbion.com
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Scientific contact |
Olivier Poirot, Axalbion SA, +41 76 341 81 38, opoirot@axalbion.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Jun 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Jun 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the effectiveness of AX-8 for the treatment of refractory chronic cough (RCC) and associated upper airway symptoms after one dose of treatment in reducing awake cough frequency compared to baseline, for the purpose of planning a future randomised controlled trial.
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Protection of trial subjects |
The study was performed in accordance with the current version of the declaration of Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000). The study was conducted in agreement with the International Conference on Harmonisation (ICH) guidelines on Good Clinical Practice (GCP). All subjects provided written informed consent to participate in the study prior to being screened.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Dec 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
12 subjects were enrolled in the United Kingdom. | ||||||||||
Pre-assignment
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Screening details |
16 subjects were screened for the study and 12 received study drug. | ||||||||||
Period 1
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Period 1 title |
Screening (Visit 1)
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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AX-8 orally disintegrating tablet (ODT) 5 mg | ||||||||||
Arm description |
Subjects did not receive treatment during the screening period. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects did not receive treatment during the screening period.
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Period 2
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Period 2 title |
Baseline (Visit 2)
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Is this the baseline period? |
Yes [1] | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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AX-8 orally disintegrating tablet (ODT) 5 mg | ||||||||||
Arm description |
Subjects did not receive treatment during the baseline period. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects did not receive treatment during the baseline period.
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Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Period 1 was the screening period. |
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Period 3
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Period 3 title |
Treatment (Visits 3 and 4)
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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AX-8 orally disintegrating tablet (ODT) 5 mg | ||||||||||
Arm description |
Subjects received a single dose of AX-8 orally disintegrating tablet (ODT) 5 mg by mouth. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of AX-8 orally disintegrating tablet (ODT) 5 mg by mouth.
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Period 4
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Period 4 title |
Follow-up (Visit 5/Withdraw/Study End)
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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AX-8 orally disintegrating tablet (ODT) 5 mg | ||||||||||
Arm description |
Subjects did not receive treatment during the follow-up period. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects did not receive treatment during the follow-up period.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline (Visit 2)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Reporting group description |
Subjects did not receive treatment during the screening period. | ||
Reporting group title |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Reporting group description |
Subjects did not receive treatment during the baseline period. | ||
Reporting group title |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Reporting group description |
Subjects received a single dose of AX-8 orally disintegrating tablet (ODT) 5 mg by mouth. | ||
Reporting group title |
AX-8 orally disintegrating tablet (ODT) 5 mg
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Reporting group description |
Subjects did not receive treatment during the follow-up period. |
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End point title |
Change from Baseline in Objective Awake Cough Frequency Over 24 hours after 1 Dose of Treatment [1] | ||||||||||||
End point description |
The change in awake and asleep cough rates was estimated from audio recordings and calculated by taking the total number of cough events during the monitoring period while the subject was awake and dividing by the total duration (in hours) for the monitoring period the subject was awake. Any session with a recording duration < 4 hours was considered as missing. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Primary
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End point timeframe |
Baseline and 24 hours post-dose
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics are presented for this single-arm analysis. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Hourly Objective Cough Frequency Over 24 Hours After 1 Dose of Treatment | ||||||||||||||
End point description |
The change in hourly cough rates was estimated from audio recordings and calculated by taking the total number of cough events during the monitoring period (24 hours) and dividing by the total duration (in hours) for the monitoring period (24). Any session with a recording duration < 4 hours was considered as missing. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
Comparison of periods of 4, 8, and 24 hours after the installation of the cough monitor (baseline visit) with periods of 4, 8, and 24 hours after dosing (treatment visit)
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with ≥ 30% Reduction in Awake Cough Frequency per Hour | ||||||||
End point description |
The percentage of subjects with ≥ 30% of reduction from baseline in awake cough frequency is the number of subjects with ≤ -30% change in awake cough frequency divided by the total number of subjects with available data. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
24 hours post-dose
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with ≥ 30% Reduction in Cough Frequency per Hour | ||||||||||||||
End point description |
The percentage of subjects with ≥ 30% reduction from baseline in 24-cough frequency is the number of subjects with ≤ -30% change in cough frequency divided by the total number of subjects with available data. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
Periods of 4, 8, and 24 hours post-dose
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Cough Severity Visual Analogue Scale (VAS) | ||||||||||||||||||||||||||||||||||||||
End point description |
Subjects rated cough severity 30 mins before cough monitor installation or dosing, on baseline and treatment days, respectively, and then hourly for 6 hours using a 100-mm visual analogue scale (VAS). The VAS for the first 4 hours were recorded in the clinic and the last 2 hours were recorded at home using a patient diary. The subject's impression at a time point during the baseline visit was compared to the overall impression during more than a 24-hour period. Therefore, the value >24h is an overall impression at a specific time point. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) and up to ≥24 hours post-dose (Day 1)
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Urge-to-Cough VAS | ||||||||||||||||||||||||||||||||||||||
End point description |
Subjects rated urge-to-cough 30 mins before cough monitor installation or dosing, on baseline and treatment days, respectively, and then hourly for 6 hours using a 100-mm visual analogue scale (VAS). The VAS for the first 4 hours were recorded in the clinic and the last 2 hours were recorded at home using a patient diary. The subject's impression at a time point during the baseline visit was compared to the overall impression during more than a 24-hour period. Therefore, the value >24h is an overall impression at a specific time point. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) and up to ≥24 hours post-dose (Day 1)
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Throat Irritation VAS | ||||||||||||||||||||||||||||||||||||||
End point description |
Subjects rated cough severity 30 mins before cough monitor installation or dosing, on baseline and treatment days, respectively, and then hourly for 6 hours using a 100-mm visual analogue scale (VAS). The VAS for the first 4 hours were recorded in the clinic and the last 2 hours were recorded at home using a patient diary. The subject's impression at a time point during the baseline visit was compared to the overall impression during more than a 24-hour period. Therefore, the value >24h is an overall impression at a specific time point. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) and up to ≥24 hours post-dose (Day 1)
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No statistical analyses for this end point |
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End point title |
Throat Cooling VAS | ||||||||||||||||||||||||||||||
End point description |
Subjects rated cough severity 30 mins before cough monitor installation or dosing, on baseline and treatment days, respectively, and then hourly for 6 hours using a 100-mm visual analogue scale (VAS). The VAS for the first 4 hours were recorded in the clinic and the last 2 hours were recorded at home using a patient diary. The subject's impression at a time point during the baseline visit was compared to the overall impression during more than a 24-hour period. Therefore, the value >24h is an overall impression at a specific time point. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period.
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End point type |
Secondary
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End point timeframe |
Up to ≥24 hours post-dose (Day 1)
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No statistical analyses for this end point |
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End point title |
Global Rating of Change Scale (GRCS) - Cough Frequency | ||||||||||||||||||
End point description |
Subjects assessed overall status of cough frequency since dosing using the GRCS instrument, with 3 categories and a 14-point scale range: better (1-7), about the same, and worse (8-14). GRCS were measured 4h post-dose on Treatment Day 1 and 24h post-dose on Treatment Day 2. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period. pd=post-dose.
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End point type |
Secondary
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End point timeframe |
4h post-dose on Treatment Day 1 and 24h post-dose on Treatment Day 2
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No statistical analyses for this end point |
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End point title |
Global Rating of Change Scale (GRCS) - Cough Severity | ||||||||||||||||||
End point description |
Subjects assessed overall status of cough severity since dosing using the GRCS instrument, with 3 categories and a 14-point scale range: better (1-7), about the same, and worse (8-14). GRCS were measured 4h post-dose on Treatment Day 1 and 24h post-dose on Treatment Day 2. The full analysis set included all enrolled subjects who took at least one dose of study medication and provided at least one baseline and at least one post-baseline primary endpoint observation during the treatment period. pd=post-dose.
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End point type |
Secondary
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End point timeframe |
4h post-dose on Treatment Day 1 and 24h post-dose on Treatment Day 2
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) | ||||||||
End point description |
TEAEs were defined as AEs with a date of onset on or after first study medication intake. The incidence of TEAEs was classified by system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA). For incidence reporting, if a subject reported more than one AE that was coded to the same system organ class or preferred term, the subject was counted only once for that specific system organ class or preferred term. The safety analysis set consisted of all enrolled subjects who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Approximately 30 days
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Serious Adverse Events (SAEs) | ||||||||
End point description |
SAEs were defined as AEs that resulted in death, threat to life, hospitalization, persistent or significant incapacity, congenital anomaly/birth defect, or important medical event that was considered serious by the investigator or Sponsor or would require medical/surgical intervention to prevent any of the prior outcomes. The safety analysis set consisted of all enrolled subjects who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Approximately 30 days
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Approximately 30 days
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Adverse event reporting additional description |
The safety analysis set consisted of all enrolled subjects who received at least one dose of study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
AX-8
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Reporting group description |
Subjects received a single dose of AX-8 orally disintegrating tablet (ODT) 5 mg by mouth. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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26 Jan 2018 |
The following substantial changes have been made to the protocol:
Blood sampling for pharmacokinetic (PK) analysis was added (+15, +30 mins, +1, +1.25, +1.5, +1.75, +2, +2.5, +3, +3.5 hours).
PK sample will be taken anytime pre-dose on Day 1, post-dose + 15, +30, +45 minutes, +1, +1.25, +1.5, +1.75, +2, +2.5, +3, +3.5, +4 hours (i.e., 1hr, 1hr15 mins, 1hr30mins, 1hr45mins, 2hr, 2hr30mins, 3hr, 3hr30mins, 4hr).
PK analysis changed from being a secondary endpoint to being an exploratory endpoint. Synopsys updated: Study Objectives completed and section “Exploratory Endpoint” added. Section 2 – Study Objectives. New paragraph “Exploratory Objectives” added.
New section 3.3.4 – Exploratory Endpoint. The patient information sheet (PIS) has been updated in line with these protocol changes. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |