E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Cohorts 1 and 2: To assess the safety, tolerability, and pharmacokinetics (PK) of multiple doses of inhaled QBW276 and its metabolites, over 1 or 2 weeks of treatment in patients with cystic fibrosis regardless of the underlying mutation
Cohort 3: To evaluate the pharmacodynamic (PD) response to multiple doses of inhaled QBW276 in lung function (percent of predicted FEV1) over 4 weeks of treatment compared with placebo in patients with cystic fibrosis that are homozygous for the F508del mutation |
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E.2.2 | Secondary objectives of the trial |
Cohorts 1 and 2: To evaluate the PD response to multiple doses of inhaled QBW276 on change in lung function over 1 or 2 weeks of treatment from baseline compared with placebo in patients with CF
Cohort 3: To assess the safety, tolerability, PK and PD of multiple doses of inhaled QBW276 and its metabolites over 4 weeks of treatment per period in patients with cystic fibrosis who are homozygous for the F508del mutation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Cohorts 1 and 2 = any genotype on any standard of care treatment
- Cohort 3 = F508del homozygotes on standard of care at that time
- FEV1 between 40 and 100%
- LCI2.5 ≥ 8 if FEV1 is more than 80%
Other protocol-defined inclusion/exclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
- Adrenal or electrolyte abnormalities
- Lung transplant
- Autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc.)
Other protocol-defined inclusion/exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cohorts 1 and 2:
All safety assessments during the cohort period:
- Physical examination
- Hematology
- Blood chemistry (central and local labs)
- Urinalysis
- ECG evaluation
- Vital Signs
- AEs and SAEs
- PK measurements
Cohort 3:
- % predicted FEV1 (assessed by spirometry) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cohort 1: 1 week;
Cohort 2: 2 weeks;
Cohort 3: 4 Weeks |
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E.5.2 | Secondary end point(s) |
Cohort 1 and 2:
- % predicted FEV1 (assessed by spirometry)
- LCI2.5 (assessed by Multiple Breath Nitrogen Washout [MBNW]) if
FEV1 at screening is > 80% of predicted
Cohort 3:
All safety assessments during the cohort period, including:
- Physical examination
- Hematology
- Blood chemistry
- Urinalysis
- ECG evaluation
- Vital Signs
- AEs and SAEs
- LCI2.5 (assessed by MBNW) if FEV1 at screening is > 80% of predicted
- PK measurements |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cohort 1: 7 days;
Cohort 2: 14 days;
Cohort 3: 12 Weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Study completion is defined as when the last patient completes their End of Study visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator, or in the event of an early study termination decision, the date of that decision. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |