Phase 2
Completed N=67
A Dose Ranging Study With CHF 1531 in Subjects With Asthma (FLASH)
Source: ClinicalTrials.gov NCT03086460 ↗Enrolled (actual)
67
Serious AEs
0.0%
Results posted
Aug 2021
Primary outcomePrimary: FEV1 Area Under the Curve Between 0 and 12 h [AUC(0-12h)], Normalized by Time -- Change From Baseline to Post Dose Day 14 — 0.174; 0.221; 0.197; 0.231 Litres — p=<0.001
Summary
To evaluate the dose-response of different doses of CHF 1531 pressurized metered dose inhaler (pMDI) containing formoterol fumarate, on lung function and other clinical outcomes and to identify the optimal dose(s) with regard to benefit/ risk ratio for further development in the target subject population.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY FEV1 Area Under the Curve Between 0 and 12 h [AUC(0-12h)], Normalized by Time -- Change From Baseline to Post Dose Day 14 |
0.174; 0.221; 0.197; 0.231; 0.064; 0.208 | <0.001 sig |
| PRIMARY Sensitivity Analysis 1: FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 14 |
0.169; 0.224; 0.196; 0.232; 0.058; 0.206 | <0.001 sig |
| PRIMARY Sensitivity Analysis 2: FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 14 |
0.129; 0.180; 0.159; 0.179; -0.006; 0.170 | <0.001 sig |
| PRIMARY Sensitivity Analysis 3: FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 14 |
0.144; 0.194; 0.170; 0.198; 0.037; 0.184 | <0.001 sig |
| SECONDARY FEV1 AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 1 |
0.181; 0.221; 0.260; 0.282; 0.067; 0.239 | <0.001 sig |
| SECONDARY FEV1 AUC(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14 |
0.220; 0.250; 0.270; 0.317; 0.047; 0.288 | <0.001 sig |
| SECONDARY FEV1 Peak(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14 |
0.359; 0.370; 0.393; 0.430; 0.178; 0.416 | <0.001 sig |
| SECONDARY FVC AUC(0-12h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14 |
0.111; 0.156; 0.160; 0.182; 0.059; 0.172 | 0.098 |
| SECONDARY FVC AUC(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14 |
0.158; 0.186; 0.159; 0.215; 0.036; 0.213 | <0.001 sig |
| SECONDARY FVC Peak(0-4h), Normalized by Time -- Change From Baseline to Post Dose Day 1 and Day 14 |
0.331; 0.347; 0.354; 0.367; 0.216; 0.385 | 0.003 sig |
| SECONDARY Pre-dose Morning FEV1 (L) -- Change From Baseline to Post Dose Day 14 |
0.071; 0.102; 0.073; 0.149; 0.037; 0.126 | 0.361 |
| SECONDARY Pre-dose Morning FVC -- Change From Baseline to Post Dose Day 14 |
0.048; 0.044; 0.048; 0.114; 0.053; 0.114 | 0.896 |
| SECONDARY Time to Onset of Action -- Change From Baseline in Post-dose FEV1 ≥12% and ≥200 mL to Post Dose Day 1 |
358.8; 60.3; 33.6; 44.3; NA; 45.5 | <0.001 sig |
| SECONDARY Patients Achieving Onset of Action -- Change From Baseline in Post-dose FEV1 ≥12% and ≥200 mL to Post Dose Day 1 |
23; 22; 30; 29; 11; 31 | — |
| SECONDARY Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) -- Change From Baseline for Post-dose on Day 1 and on Day 14 |
-1.2; 0.2; -0.8; -1.2; -0.5; -0.8 | — |
| SECONDARY 12-lead ECG Parameter -- Heart Rate (HR) -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
0.3; 1.2; 1.7; 2.5; -2.4; -0.3 | — |
| SECONDARY Heart Rate (HR) AUC(0-4h), Normalized by Time -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
0.2; 0.8; 2.7; 3.0; -1.0; 0.3 | — |
| SECONDARY Heart Rate (HR) Peak(0-4h), Normalized by Time -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
4.7; 4.4; 6.5; 7.5; 2.9; 5.1 | — |
| SECONDARY Heart Rate (HR) AUC(0-4h) and Peak(0-4h), Normalized by Time -- Change From Pre-dose to Post Dose Day 14 |
-0.4; 0.5; 0.4; 1.3; -0.2; 0.9 | — |
| SECONDARY 12-lead Electrocardiogram (ECG) Parameter (QTcF Interval) -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
3.9; 3.8; 2.7; 4.9; -0.2; 1.4 | — |
| SECONDARY 12-lead Electrocardiogram (ECG) Parameter (PR Interval) -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
-0.1; 1.6; -1.3; -3.6; 1.0; 3.2 | — |
| SECONDARY 12-lead Electrocardiogram (ECG) Parameter (QRS Interval) -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
1.2; 1.2; 1.7; 1.1; 0.8; 1.3 | — |
| SECONDARY Serum Potassium -- Change From Baseline Post-dose to Post Dose Day 1 and Day 14 |
-0.01; -0.05; -0.08; -0.17; -0.06; -0.18 | — |
| SECONDARY Serum Glucose -- Change From Baseline to Post-dose Day 1 and Day 14 |
0.49; 0.34; 0.57; 1.19; 0.47; -0.06 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female subjects aged ≥18 and ≤75 years who have signed an Informed Consent Form prior to initiation of any study-related procedure.
- A diagnosis of asthma as defined in the Global Initiative for Asthma (GINA) Report, 2016, documented for at least 1 year prior to screening.
- Poorly controlled or uncontrolled asthma evidenced by a score ≥1.5 on the Asthma Control Questionnaire 7 © (ACQ-7)
- A pre-bronchodilator Forced Expiratory Volume in the 1st Second ( FEV1) ≥60% and 10 pack-years or having stopped smoking one year or less prior to screening visit.
- History of life-threatening asthma, clinically significant uncontrolled disease or respiratory infection.
- An asthma exacerbation requiring oral/intravenous corticosteroids ≤ 30 days, intramuscular depot corticosteroid ≤3 months or hospitalization within 6 months prior to screening.
- Subjects with unresolved bacterial or viral respiratory tract, sinus, or middle ear infection affecting asthma status within 2 weeks prior to screening.
- Subjects who received a vaccination within 2 weeks prior to screening or during the run-in.
- Subjects with oral candidiasis at screening and at randomization.
- Subjects with any clinically significant, uncontrolled condition.
- Subjects with serum potassium levels 450 ms for males or QTcF >470 ms for females at screening or randomization visits.
- Subjects with known intolerance/hypersensitivity or contra-indication to treatment with inhaled β2-adrenergic receptor agonists, corticosteroids or propellant gases/excipients.
- Subjects with concomitant immunosuppressive therapy, use of oral or injected corticosteroids, anti- Immunoglobulin E (IgE), anti-Interleukin 5 (IL5) or other monoclonal or polyclonal antibodies within 12 weeks prior to screening.
- Use of potent cytochrome P450 3A4 inhibitors and inducers within 4 weeks prior to screening.
- History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening.
- Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial.
- Subjects who are mentally or legally incapacitated or subjects accommodated in an establishment as a result of an official or judicial order.
- Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.
Data sourced from ClinicalTrials.gov (NCT03086460). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.