Phase 2
N=733
A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease
COPD · Chronic Obstructive Pulmonary Disease
Bottom Line
View on ClinicalTrials.gov: NCT03084796 ↗Enrolled (actual)
733
Serious AEs
1.5%
Results posted
Jun 2021
Primary outcome: Primary: Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6 — 0.070; 0.118; 0.153; 0.147 Litres — p=0.037
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- CHF 5259 (Drug); Placebo (Drug); Tiotropium Bromide 18 µg Inhalation Capsule (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Chiesi Farmaceutici S.p.A.
- Primary completion
- May 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6 |
0.070; 0.118; 0.153; 0.147; 0.002; 0.213 | 0.037 sig |
| SECONDARY Change From Baseline in FEV1 AUC(0-12h) Normalized by Time on Day 1 |
0.067; 0.086; 0.135; 0.149; 0.009; 0.192 | 0.002 sig |
| SECONDARY Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6 |
0.101; 0.115; 0.173; 0.190; 0.030; 0.194 | <0.001 sig |
| SECONDARY Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6 |
0.197; 0.211; 0.260; 0.288; 0.136; 0.299 | 0.002 sig |
| SECONDARY Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6 |
0.086; 0.133; 0.195; 0.220; 0.011; 0.305 | 0.029 sig |
| SECONDARY Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6 |
0.133; 0.192; 0.244; 0.273; 0.036; 0.311 | 0.003 sig |
| SECONDARY Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6 |
0.293; 0.372; 0.414; 0.455; 0.213; 0.491 | 0.035 sig |
| SECONDARY Time to Onset of Action (Change From Baseline in Post-dose FEV1 ≥ 100 mL) on Day 1 |
45.1; 32.6; 29.5; 27.3; 240.1; 28.1 | 0.002 sig |
| SECONDARY Number of Patients Achieving Onset of Action - Change From Baseline in Post-dose FEV1 ≥100 mL on Day 1 |
90; 103; 103; 110; 74; 113 | — |
| SECONDARY Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6 |
0.059; 0.080; 0.122; 0.111; 0.000; 0.122 | 0.017 sig |
| SECONDARY Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6 |
0.156; 0.137; 0.106; 0.140; 0.047; 0.090 | 0.023 sig |
| SECONDARY Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6 |
70; 78; 75; 84; 67; 74 | 0.848 |
| SECONDARY Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6 |
1.29; 1.55; 1.54; 1.94; 1.14; 1.66 | 0.666 |
| SECONDARY Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period |
16.78; 15.67; 15.55; 18.19; 8.90; 13.51 | 0.022 sig |
| SECONDARY Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period |
-0.72; -0.58; -0.53; -0.71; -0.30; -0.52 | <0.001 sig |
| SECONDARY Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period |
-1.681; -1.539; -1.941; -1.663; -0.714; -1.280 | 0.016 sig |
| SECONDARY Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) |
-1.4; -0.4; -2.0; -1.9; -0.9; -1.2 | — |
| SECONDARY Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR) |
-8.85; -6.62; -7.78; -7.64; -4.84; -5.54 | — |
| SECONDARY Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval |
7.24; 6.53; 6.08; 6.71; 3.06; 4.90 | — |
| SECONDARY Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval |
1.18; 0.05; 1.50; 1.99; 0.45; 1.50 | — |
| SECONDARY Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF) |
3.62; 5.37; 6.81; 6.25; 3.59; 5.56 | — |
| SECONDARY 24-hour Holter ECG - Prolonged QTcF - Male Subjects |
1; 0; 0; 1; 2; 1 | — |
| SECONDARY 24-hour Holter ECG - Prolonged QTcF - Female Subjects |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY 24-hour Holter ECG - Prolonged QTcF - Change From Baseline |
19; 20; 21; 20; 16; 18 | — |
Summary
The purpose of this study is to evaluate the dose-response of different doses of CHF 5259 pMDI on lung function and other clinical outcomes, to identify the optimal dose(s) in terms of benefit/ risk ratio for further development in the target subject population.
Eligibility Criteria
Inclusion Criteria
- Male or female subjects aged ≥ 40 who have signed an Informed Consent Form prior to initiation of any study-related procedure.
- Subjects with a diagnosis of COPD (according to GOLD 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD Report) at least 12 months before the screening visit.
- Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
- A post-bronchodilator forced expiratory volume in the 1st second (FEV1) ≥50% and 450 ms for males or QTcF >470 ms for females at screening visit
- Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would prevent use of anticholinergic agents
- History of hypersensitivity to M3 receptor antagonists, β2-adrenergic receptor agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impact the efficacy of the study treatment according to the Investigator's judgement
- Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study treatment according to Investigator's judgement
- Subjects with serum potassium levels <3.5 mEq/L (or 3.5 mmol/L) at screening
- Use of potent cytochrome P450 2D6 and 3A4 inhibitors within 4 weeks prior to screening
- Unstable or uncontrolled concurrent disease; fever, endocrine disease, gastrointestinal disease; neurological disease; hematological disease; autoimmune disorders, or other which may impact the feasibility of the results of the study according to Investigator's judgment
- 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 (NCT03084796). 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.