moderate to severe Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 20.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: RPL554
Product Code: RPL554
Pharmaceutical Form: Nebuliser suspension
CAS Number: 298680-25-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration nu
Sponsors
Verona Pharma plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female aged between 40 and 75 years inclusive - Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg. - COPD diagnosis: Patients with a clinical diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year prior to screening. - Ability to perform acceptable and reproducible spirometry. Post-bronchodilator (albuterol/salbutamol four puffs) spirometry at screening must demonstrate a: • Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of =0.70 • Post-bronchodilator FEV1 =40 % and =80% of predicted normal - Clinically stable COPD in the 4 weeks prior to screening and randomization - For patients taking long acting bronchodilators, capable of withdrawing from these medications until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study medication Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: - A history of life-threatening COPD including Intensive Care Unit admission and requiring intubation. - COPD exacerbation requiring oral steroids in the 3 months prior to screening or prior to randomization; hospitalizations for COPD in the 6 months prior to screening. - Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases. - Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) in the 3 months prior to screening and throughout the study, use of beta blockers, requirement for oxygen therapy. - Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant. - Documented cardiovascular disease: arrhythmias, unstable angina, recent or suspected myocardial infarction within 6 months prior to screening, congestive heart failure, a history of unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months. - Abnormal clinically significant 12 lead Holter findings, including but not limited to: • Premature ventricular contractions (PVCs) >1000 in 24 hour period • Sustained ventricular tachycardia >6 beats • Atrial fibrillation with rapid ventricular response (>100 bpm) • Atrial flutter • Sinus pause >2 seconds - Other protocol defined criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of RPL554 or placebo on change from baseline in peak forced expiratory volume in 1 second (FEV1) when administered to patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD);Secondary Objective: • To investigate the effect of RPL554 or placebo on change from baseline in morning trough FEV1 when administered to patients with moderate to severe COPD. • To investigate the bronchodilator effect of RPL554 or placebo on peak and average FEV1 at first dose; over 3 hours at Weeks 1 to 4. • To investigate the the effects of RPL554 or placebo on COPD symptoms, as measured by daily diary, patient scales and questionnaires • To investigate the safety of RPL554 when administered for 4 weeks in patients with COPD, as measured by adverse events, electrocardiograms (ECGs), Holter monitoring and vital signs • To compare the amount of rescue albuterol/salbutamol use required;Primary end point(s): Change from baseline in peak FEV1 (maximum value during 3 hours following dose) after 4 weeks of treatment.;Timepoint(s) of evaluation of this end point: 4 weeks on treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in morning trough FEV1 after 4 weeks of treatment • Change from baseline in average FEV1 over 12 hours at Visits 2 and 6 • Change from baseline in peak and average FEV1 over 3 hours at Visits 2 to 6 • Change from baseline in COPD symptoms, as measured by daily diary • Change from baseline in the protocol defined breathlessness scales. • Change from baseline in rescue medication use • Safety and tolerability parameters as defined in protocol section 9.2.1.2 ;Timepoint(s) of evaluation of this end point: 4 weeks on treatment, visits 3 to 6 | — |
Countries
Bulgaria, Czech Republic, Germany, Poland, Romania, United Kingdom, United States
Contacts
Public ContactProject Management
Verona Pharma plc
Outcome results
None listed