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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-000375-16 | EudraCT Number |
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Trial was terminated due to the impact of the COVID-19 on trial activities. 68 patients with refractory chronic cough were enrolled with 52 completing treatment
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This is a multi-center, randomized, double-blind, placebo-controlled, crossover, dose escalation study of BLU-5937 in subjects with unexplained or refractory chronic cough
This study will have two 16-day treatment periods (four escalating doses or matching placebo at four days interval) separated by a 10 to 14-day washout period. There will be a 14-day follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BLU-5937 oral tablet BID | Experimental | Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID |
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| Placebo oral tablet BID | Placebo Comparator | Randomized crossover design of matching placebo tablets to be administered orally BID |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BLU-5937 | Drug | Four escalating doses of BLU-5937 administered BID over the course of the study |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Awake Objective Cough Frequency on Log-transformed Scale | Change in awake cough frequency (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected | Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = 20 Coughs/Hour at Baseline | Change in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency > or = 20 coughs/hour at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jacky Smith, MD, Ph.D. | University of Manchester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Allergy Associates Medical Group Inc. | San Diego | California | 92108 | United States | ||
| Allergy & Asthma Associates of Santa Clara Valley |
A total of 68 participants were randomized to receive the study drug (BLU-5937) followed by placebo (33 participants) or placebo followed by the study drug (35 participants).
Participants were recruited at 16 clinical trial sites in the United-Kingdom and in United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | BLU-5937 > Placebo | Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID BLU-5937: Four escalating doses of BLU-5937 administered BID over the course of the study followed by matching Placebo |
| FG001 | Placebo > BLU-5937 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 26, 2019 |
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Two-arm, Two-Period, crossover assignment
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| Placebo | Drug | Matching placebo for BLU-5937 |
|
| Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses |
| Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = Median (32.4 Coughs/Hour) at Baseline | Change in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency > or = median (32.4 coughs/hour) at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected | Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12,16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses |
| San Jose |
| California |
| 95117 |
| United States |
| Centre for Cough | Largo | Florida | 33778 | United States |
| Clinical Research Institute | Minneapolis | Minnesota | 55402 | United States |
| Clinical Research of Gastonia | Gastonia | North Carolina | 20854 | United States |
| National Allergy & Asthma Research | Charleston | South Carolina | 29420 | United States |
| Diagnostics Research Group | San Antonio | Texas | 78229 | United States |
| Allergy Asthma & Sinus Center | Greenfield | Wisconsin | 53228 | United States |
| Belfast City Hospital | Belfast | BT9 7BL | United Kingdom |
| Castle Hill Hospital | Cottingham | HU16 5JQ | United Kingdom |
| University Hospitals of Leicester | Leicester | LE3 9QP | United Kingdom |
| Prince Phillip Hospital | Llanelli | SA14 8QF | United Kingdom |
| King's College Hospital | London | SE5 9RS | United Kingdom |
| Royal Brompton Hospital | London | SW3 6HP | United Kingdom |
| Manchester Clinical Research Facility | Manchester | M23 9LT | United Kingdom |
| North Tyneside General Hospital | North Shields | NE29 8NH | United Kingdom |
Randomized crossover design of matching placebo tablets to be administered orally BID Placebo: Matching placebo for BLU-5937 follow by four escalating doses of BLU-5937 |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 |
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The baseline analysis population consisted of all randomized participants who have received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | BLU-5937 > Placebo | Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID BLU-5937: Four escalating doses of BLU-5937 administered BID over the course of the study followed by matching Placebo |
| BG001 | Placebo > BLU-5937 | Randomized crossover design of matching placebo tablets to be administered orally BID Placebo: Matching placebo for BLU-5937 followed by four escalating doses of BLU-5937 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Change in Awake Objective Cough Frequency on Log-transformed Scale | Change in awake cough frequency (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected | Analysis population consisted of all randomized subjects who took at least one dose of study drug and provided at least one baseline and at least one post-baseline cough frequency measurement | Posted | Least Squares Mean | 95% Confidence Interval | Log coughs/hour | Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses |
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| Other Pre-specified | Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = 20 Coughs/Hour at Baseline | Change in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency > or = 20 coughs/hour at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected | Posted | Least Squares Mean | 95% Confidence Interval | Log coughs/hour | Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses |
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| Other Pre-specified | Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = Median (32.4 Coughs/Hour) at Baseline | Change in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency > or = median (32.4 coughs/hour) at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected | Posted | Least Squares Mean | 95% Confidence Interval | Log coughs/hour | Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12,16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses |
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All-cause mortality and Adverse Event data collection is up to 11 weeks
Analysis population consisted of all randomized participants who received at least 1 dose of study drug
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BLU-5937 - 25 mg | BLU-5937 25 mg tablet administered orally BID for 4 days | 0 | 61 | 0 | 61 | 10 | 61 |
| EG001 | BLU-5937 - 50 mg | BLU-5937 50 mg tablet administered orally BID for 4 days | 0 | 61 | 0 | 61 | 14 | 61 |
| EG002 | BLU-5937 - 100 mg | BLU-5937 100 mg tablet administered orally BID for 4 days | 0 | 60 | 0 | 60 | 15 | 60 |
| EG003 | BLU-5937 - 200 mg | BLU-5937 200 mg tablet administered orally BID for 4 days | 0 | 58 | 0 | 58 | 10 | 58 |
| EG004 | Placebo | Matching Placebo for BLU-5937 administered orally BID for 4 days | 0 | 61 | 1 | 61 | 19 | 61 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| colorectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.0 | Non-systematic Assessment | colorectal cancer considered as not related to study drug was reported approximately 6 months after the last dose of study medication. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA v23.0 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA v23.0 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v23.0 | Non-systematic Assessment |
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No data collected as part of this study will be utilized in any written work, including publications, without the written consent of sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director Clinical Development | Bellus Health Inc | 833-703-0708 | lharvey@bellushealth.com |
| Jul 5, 2021 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000096822 | Chronic Cough |
| ID | Term |
|---|---|
| D003371 | Cough |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000657411 | BLU-5937 |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Mixed Models Analysis | Intention To Treat (ITT), statistical analysis follows a Mixed Model which uses log-transformation | 0.4602 | Estimated percent change | -6.1 | 2-Sided | 95 | -20.8 | 11.2 | Percent change difference between BLU-5937 and placebo was estimated by 100 x [e^diff - 1] where 'e' = exponent of difference; and 'diff' = the treatment mean difference from mixed model of change from baseline based on log-transformed data. | Superiority |
| Mixed Models Analysis | Intention To Treat (ITT), statistical analysis follows a Mixed Model which uses log-transformation | 0.4181 | Estimated percent change | -7.8 | 2-Sided | 95 | -24.4 | 12.5 | Percent change difference between BLU-5937 and placebo was estimated by 100 x [e^diff - 1] where 'e' = exponent of difference; and 'diff' = the treatment mean difference from mixed model of change from baseline based on log-transformed data. | Superiority |
| Mixed Models Analysis | Intention To Treat (ITT), statistical analysis follows a Mixed Model which uses log-transformation | 0.0855 | Estimated percent change | -16.7 | 2-Sided | 95 | -32.3 | 2.6 | Percent change difference between BLU-5937 and placebo was estimated by 100 x [e^diff - 1] where 'e' = exponent of difference; and 'diff' = the treatment mean difference from mixed model of change from baseline based on log-transformed data. | Superiority |
| OG004 | BLU-5937 - 100 mg | BLU-5937 100 mg tablet administered orally BID for 4 days |
| OG005 | Placebo Comparator - 100 mg | Matching Placebo for BLU-5937 administered orally BID for 4 days |
| OG006 | BLU-5937 - 200 mg | BLU-5937 200 mg tablet administered orally BID for 4 days |
| OG007 | Placebo Comparator - 200 mg | Matching Placebo for BLU-5937 administered orally BID for 4 days |
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Matching Placebo for BLU-5937 administered orally BID for 4 days
| OG004 | BLU-5937 - 100 mg | BLU-5937 100 mg tablet administered orally BID for 4 days |
| OG005 | Placebo Comparator - 100 mg | Matching Placebo for BLU-5937 administered orally BID for 4 days |
| OG006 | BLU-5937 - 200 mg | BLU-5937 200 mg tablet administered orally BID for 4 days |
| OG007 | Placebo Comparator - 200 mg | Matching Placebo for BLU-5937 administered orally BID for 4 days |
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