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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-004915-35 | EudraCT Number |
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This is a study of multiple doses of inhaled QBW276 in patients with cystic fibrosis on top of standard of care. The study was divided into 3 Cohorts. Cohorts 1 and 2 are designed to be a randomized, double-blind, placebo-controlled, parallel arm, multiple dose study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of inhaled QBW276 over 1 week (cohort 1) or 2 weeks (cohort 2) in patients with cystic fibrosis regardless of their genotype.
The study was terminated after Cohort 2 due to the resource issues.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CQBW276 | Experimental | Cohorts 1 and 2 will enroll 8 patients each (6:2 QBW276 and placebo, respectively). Cohort 1: dose is 3 mg bid (6 mg daily) QBW276 or placebo for 7 days. Cohort 2: dose and frequency will be confirmed after cohort 1 is complete. The duration is 14 days. Cohort 3: dose and frequency will be confirmed after cohort 2 is complete. The duration is approximately 4 months. Patients will be randomized to one of two treatment sequences: QBW276 in Period 1 and Placebo in Period 2 or Placebo in Period 1 and QBW276 in Period 2. Twenty four patients are required to complete cohort 3. |
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| Placebo | Placebo Comparator | Cohorts 1 and 2 will enroll 8 patients each (6:2 QBW276 and placebo, respectively). Cohort 1: dose is 3 mg bid (6 mg daily) QBW276 or placebo for 7 days. Cohort 2: dose and frequency will be confirmed after cohort 1 is complete. The duration is 14 days. Cohort 3: dose and frequency will be confirmed after cohort 2 is complete. The duration is approximately 4 months. Patients will be randomized to one of two treatment sequences: QBW276 in Period 1 and Placebo in Period 2 or Placebo in Period 1 and QBW276 in Period 2. Twenty four patients are required to complete cohort 3. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Other | Placebo |
| |
| QBW276 |
| Measure | Description | Time Frame |
|---|---|---|
| Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated | Cohort 1: day 1-7; Cohort 2: day 1-14 |
| Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Blood collection will be used to observe the maximum plasma concentration (Cmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Cmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Cmax on Days 7 or 14 correspond to Cmax,ss | Cohort 1: day 1, 7; Cohort 2: day 1, 14 |
| Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Blood collection will be used to observe the maximum plasma concentration (Tmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Tmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Tmax on Days 7 or 14 correspond to Tmax,ss | Day 1, 7 and 14 |
| Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Blood collection will be used to observe the maximum plasma concentration (AUCtau) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The AUCtau, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, AUCtau on Days 7 or 14 correspond to AUClast,ss |
| Measure | Description | Time Frame |
|---|---|---|
| Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1) | To evaluate the response to multiple doses of inhaled QBW276 in percent predicted forced expiratory volume in the first second by spirometry according to international standards over 1 or 2 weeks of treatment compared with placebo in patients with cystic fibrosis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | New York | New York | 10032 | United States | ||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
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The study was terminated after completion of all randomized patients in Cohort 2 due to strategic issues. All patients completed the study prior to termination.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 QBW276 | QBW276 3mg bid |
| FG001 | Cohort 2 QBW276 | QBW276 6mg bid |
| FG002 | Placebo | Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 QBW276 | QBW276 3mg bid |
| BG001 | Cohort 2 QBW276 | QBW276 6mg bid |
| BG002 |
| 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 |
| 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 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated | Safety set: The safety analysis set included all patients that received any study drug | Posted | Number | Participants | Cohort 1: day 1-7; Cohort 2: day 1-14 |
|
Up to 18 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 | Cohort 1 QBW276 | QBW276 3 mg bid | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceutical | 862-778-8300 | novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 20, 2017 | Apr 15, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jun 28, 2018 | Apr 15, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| Drug |
0.3 mg and 1.5 mg strengths |
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| Day 1, 7 and 14 |
| Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | The accumulation ratio (Racc) will be reported using blood samples taken on days 1 -7 in cohort 1 and days 1-14 in cohort 2. Accumulation ratio (Racc) for QBW276 and metabolites was not calculated by PK software for patients where BLOQ values were observed for all blood samples in their PK profile. | Cohort 1: 7 days; Cohort 2: 14 days |
| Baseline to End of study (EOS) |
| Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2. | Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards | Baseline to EOS |
| Dallas |
| Texas |
| 75390-9034 |
| United States |
| Novartis Investigative Site | Cologne | 50924 | Germany |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Placebo |
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2. |
| BG003 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Placebo |
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2. |
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| Primary | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Blood collection will be used to observe the maximum plasma concentration (Cmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Cmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Cmax on Days 7 or 14 correspond to Cmax,ss | Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | ng/mL | Cohort 1: day 1, 7; Cohort 2: day 1, 14 |
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| Primary | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Blood collection will be used to observe the maximum plasma concentration (Tmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Tmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Tmax on Days 7 or 14 correspond to Tmax,ss | Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data. | Posted | Median | Full Range | hr | Day 1, 7 and 14 |
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| Primary | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Blood collection will be used to observe the maximum plasma concentration (AUCtau) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The AUCtau, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, AUCtau on Days 7 or 14 correspond to AUClast,ss | Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | hr*ng/mL | Day 1, 7 and 14 |
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| Primary | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | The accumulation ratio (Racc) will be reported using blood samples taken on days 1 -7 in cohort 1 and days 1-14 in cohort 2. Accumulation ratio (Racc) for QBW276 and metabolites was not calculated by PK software for patients where BLOQ values were observed for all blood samples in their PK profile. | Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Error | Ratio | Cohort 1: 7 days; Cohort 2: 14 days |
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| Secondary | Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1) | To evaluate the response to multiple doses of inhaled QBW276 in percent predicted forced expiratory volume in the first second by spirometry according to international standards over 1 or 2 weeks of treatment compared with placebo in patients with cystic fibrosis. | Pharmacodynamics analysis set: The PD analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data. | Posted | Mean | Standard Deviation | Percent predicted FEV1 | Baseline to End of study (EOS) |
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| Secondary | Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2. | Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards | Pharmacodynamics analysis set: The PD analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data. | Posted | Mean | Standard Deviation | Ratio | Baseline to EOS |
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|
|
| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | Cohort 2 QBW276 | QBW276 6 mg bid | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Placebo | Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2. | 0 | 4 | 0 | 4 | 0 | 4 |
| Abdominal distension | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Feeling cold | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Mucosal dryness | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Seasonal allergy | Immune system disorders | MedDRA (21.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Blood uric acid increased | Investigations | MedDRA (21.0) | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA (21.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
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The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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