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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-002915-24 | EudraCT Number |
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This will be a randomized, double-blind, placebo-controlled study. The study will use a three-period, six-sequence, complete-block, cross-over study design to characterize two doses of inhaled TD-8236 compared to placebo in subjects with mild asthma and a known response to an allergen. Each of the three periods will be 14 days, followed by a washout period before the next period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TD-8236 Dose A (low dose) | Experimental | TD-8236 Dose A (QD x 14 days) |
|
| TD-8236 Dose B (high dose) | Experimental | TD-8236 Dose B (QD x 14 days) |
|
| Placebo | Placebo Comparator | Placebo (QD x 14 days) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TD-8236 | Drug | The study drug will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve of Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Values are reported as a weighted mean derived by calculating the AUC change from baseline over the relative time interval, divided by the time interval. | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve of Percentage Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Values are reported as a weighted mean derived by calculating the AUC percentage change from baseline over the relative time interval, divided by the time interval. | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Theravance Biopharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Theravance Biopharma Investigational Site | London | W1G 8HU | United Kingdom | |||
| Theravance Biopharma Investigational Site |
Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
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Participants were screened with an allergen challenge test within 35 days prior to first dosing. Participants received increasing concentrations of inhaled allergen until a decrease of ≥20% from preallergen forced expiratory volume (in 1 second) (FEV1) was observed during the 30 minutes following the most recent inhalation, and then monitored for a late asthmatic response (LAR).
A total of 24 participants were enrolled at 2 sites in the United Kingdom.
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| ID | Title | Description |
|---|---|---|
| FG000 | TD-8236 150 mcg/TD-8236 1500 mcg/Placebo | Participants received TD-8236 150 mcg first, then TD-8236 1500 mcg, and then Placebo. All treatment periods were 14 days with a 21 day washout period between treatments. |
| FG001 | TD-8236 150 mcg/Placebo/TD-8236 1500 mcg | Participants received TD-8236 150 mcg first, then Placebo, and then TD-8236 1500 mcg. All treatment periods were 14 days with a 21 day washout period between treatments. |
| FG002 | Placebo/TD-8236 1500 mcg/TD-8236 150 mcg | Participants received Placebo first, then TD-8236 1500 mcg, and then TD-8236 150 mcg. All treatment periods were 14 days with a 21 day washout period between treatments. |
| FG003 | Placebo/TD-8236 150 mcg/TD-8236 1500 mcg | Participants received Placebo first, then TD-8236 150 mcg, and then TD-8236 1500 mcg. All treatment periods were 14 days with a 21 day washout period between treatments. |
| FG004 | TD-8236 1500 mcg/Placebo/TD-8236 150 mcg | Participants received TD-8236 1500 mcg first, then Placebo, and then TD-8236 150 mcg. All treatment periods were 14 days with a 21 day washout period between treatments. |
| FG005 | TD-8236 1500 mcg/TD-8236 150 mcg/Placebo | Participants received TD-8236 1500 mcg first, then TD-8236 150 mcg, and then Placebo. All treatment periods were 14 days with a 21 day washout period between treatments. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants were randomized to 1 of 6 treatment sequences. Each treatment period was 14 days with a 21 day washout between treatments. All participants were randomized to receive all study drugs. |
| 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 | Area Under the Curve of Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Values are reported as a weighted mean derived by calculating the AUC change from baseline over the relative time interval, divided by the time interval. | Only participants with quantifiable measurements are included here. | Posted | Least Squares Mean | Standard Error | liters | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
|
Day 1 to end of follow-up (up to approximately 98 days)
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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 | Placebo | Participants were administered inhaled doses of placebo matching TD-8236 once per day (QD) by dry powder inhaler on Day 1 to Day 14 of the 14 day treatment period. An allergen challenge was performed 1 hour after dosing on Day 14 at the dose of allergen required to achieve a successful response at screening. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Exposure to SARS-CoV-2 | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nathan Pfeifer | Theravance Biopharma US, Inc | 001 (650) 808-3711 | npfeifer@theravance.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 5, 2019 | Feb 16, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 21, 2020 | Feb 16, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| Placebo | Drug | The placebo will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods. |
|
| Maximum Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
| Maximum Percentage Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
| Area Under the Concentration-time Curve Over One 24-hour Dosing Interval (AUC0-24) of TD-8236 in Plasma | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of TD-8236 in Plasma During Dosing Interval | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose |
| Time to Maximum Observed Concentration (Tmax) of TD-8236 in Plasma Over a Dosing Interval | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose |
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | A TEAE was defined as any adverse event (AE) that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus the number of days in the follow-up period. The severity of TEAEs were also assessed and were classified as mild, moderate or severe per the definitions below: Mild - The AE is noticeable to the participant and/or the investigator, but does not interfere with routine activity. Moderate - The AE interferes with routine activity, but responds to symptomatic therapy or rest. Severe - The AE significantly limits the participant's ability to perform routine activities despite symptomatic therapy. | Day 1 to end of follow-up (up to approximately 98 days) |
| Manchester |
| M23 9QZ |
| United Kingdom |
| Adverse Event |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| 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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| OG001 | TD-8236 150 mcg | Participants were administered 150 microgram (mcg) inhaled doses of TD-8236 once per day (QD) by dry powder inhaler on Day 1 to Day 14 of the 14 day treatment period. An allergen challenge was performed 1 hour after dosing on Day 14 at the dose of allergen required to achieve a successful response at screening. |
| OG002 | TD-8236 1500 mcg | Participants were administered 1500 microgram (mcg) inhaled doses of TD-8236 once per day (QD) by dry powder inhaler on Day 1 to Day 14 of the 14 day treatment period. An allergen challenge was performed 1 hour after dosing on Day 14 at the dose of allergen required to achieve a successful response at screening. |
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|
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| Secondary | Area Under the Curve of Percentage Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Values are reported as a weighted mean derived by calculating the AUC percentage change from baseline over the relative time interval, divided by the time interval. | Only participants with quantifiable measurements are included here. | Posted | Least Squares Mean | Standard Error | percentage change | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
|
|
|
| Secondary | Maximum Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Only participants with available data are included. | Posted | Least Squares Mean | Standard Error | liters | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
|
|
|
| Secondary | Maximum Percentage Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Only participants with available data are included. | Posted | Least Squares Mean | Standard Error | percentage change | Day 14 of treatment period: 3 to 8 hours after allergen challenge |
|
|
|
| Secondary | Area Under the Concentration-time Curve Over One 24-hour Dosing Interval (AUC0-24) of TD-8236 in Plasma | Only participants with quantifiable measurements are included here. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose |
|
|
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of TD-8236 in Plasma During Dosing Interval | Only participants with quantifiable measurements are included here. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose |
|
|
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| Secondary | Time to Maximum Observed Concentration (Tmax) of TD-8236 in Plasma Over a Dosing Interval | Only participants with quantifiable measurements are included here. | Posted | Median | Full Range | hours | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose |
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| Secondary | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | A TEAE was defined as any adverse event (AE) that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus the number of days in the follow-up period. The severity of TEAEs were also assessed and were classified as mild, moderate or severe per the definitions below: Mild - The AE is noticeable to the participant and/or the investigator, but does not interfere with routine activity. Moderate - The AE interferes with routine activity, but responds to symptomatic therapy or rest. Severe - The AE significantly limits the participant's ability to perform routine activities despite symptomatic therapy. | Only participants with available data are included. | Posted | Count of Participants | Participants | Day 1 to end of follow-up (up to approximately 98 days) |
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|
| 0 |
| 24 |
| 0 |
| 24 |
| 10 |
| 24 |
| EG001 | TD-8236 150 mcg | Participants were administered 150 microgram (mcg) inhaled doses of TD-8236 once per day (QD) by dry powder inhaler on Day 1 to Day 14 of the 14 day treatment period. An allergen challenge was performed 1 hour after dosing on Day 14 at the dose of allergen required to achieve a successful response at screening. | 0 | 23 | 0 | 23 | 9 | 23 |
| EG002 | TD-8236 1500 mcg | Participants were administered 1500 microgram (mcg) inhaled doses of TD-8236 once per day (QD) by dry powder inhaler on Day 1 to Day 14 of the 14 day treatment period. An allergen challenge was performed 1 hour after dosing on Day 14 at the dose of allergen required to achieve a successful response at screening. | 0 | 24 | 0 | 24 | 9 | 24 |
| Injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
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| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
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| Joint injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
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| Liver function test abnormal | Investigations | MedDRA (23.0) | Systematic Assessment |
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| Forced expiratory volume decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA (23.0) | Systematic Assessment |
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| Seasonal allergy | Immune system disorders | MedDRA (23.0) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
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| Episcleritis | Eye disorders | MedDRA (23.0) | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA (23.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (23.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (23.0) | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
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| Suspected COVID-19 | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
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