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The study investigates the effect of 4 weeks of twice daily treatment of four different doses of RPL554 (a phosphodiesterase [PDE]3/4 inhibitor) or placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Patients will be equally allocated to one of the five treatment options.
RPL554 is a dual inhibitor of PDE3 and PDE4 which are known to have a role in modulating the inflammatory airway response in respiratory diseases, including COPD. PDE3 inhibitors act as bronchodilators whilst PDE4 inhibitors have anti-inflammatory properties and there is also evidence to suggest that combined inhibition of PDE3 and PDE4 can have additive or synergistic anti-inflammatory and bronchodilator effects. PDE4 inhibitors (administered orally) have, however been associated with unfavorable gastrointestinal side effects such as nausea, emesis, diarrhea, abdominal pain, loss of appetite and weight loss. Dual PDE3/PDE4 inhibitors (administered by inhalation) have exhibited both bronchodilator and anti-inflammatory actions, with a more favorable side effect profile. It is plausible that increased efficacy with reduced side effects may be achievable with administration of a dual PDE3/4 inhibitor by the inhaled route compared to orally administered PDE3 or PDE4 inhibitors.
The purpose of this study is to investigate the dose response of RPL554 in patients with COPD over 4 weeks. This length of time should allow for study of the bronchodilator response, measured predominantly by the peak forced expiratory volume in one second (FEV1), and the anti-inflammatory response, as measured predominantly by trough FEV1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.75 mg RPL554 | Experimental |
| |
| 1.5 mg RPL554 | Experimental |
| |
| 3 mg RPL554 | Experimental |
| |
| 6 mg RPL554 | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RPL554 suspension | Drug | A dual PDE3/PDE 4 inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Peak FEV1 (Over 3 Hours) at Week 4 | Spirometry assessments were used to assess pulmonary function including the forced expiratory volume in 1 second (FEV1). Peak FEV1 at Week 4 was defined as the maximum post-dose value among the 30 minutes, 1, 2 and 3 hour assessments collected at Visit 6. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. A mixed model for repeated measures (MMRM) was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The least squares (LS) mean change from baseline FEV1 to peak FEV1 (as measured over 3 hours) at Week 4 is presented. | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline FEV1 to Morning Trough FEV1 at Week 4 | Morning trough FEV1 was defined as the last pre-dose value at Visit 6. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. MMRM was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The LS mean change from baseline FEV1 to morning trough FEV1 at Week 4 is presented. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dr Singh | Medicines Evaluation Unit (MEU) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinic for pneumonology | Pleven | Bulgaria | ||||
| SHATPPD-Ruse EOOD |
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Patients with a clinical diagnosis of COPD as defined by the American Thoracic Society/European Respiratory Society guidelines with symptoms compatible with COPD for at least 1 year prior to screening, and with clinically stable symptoms in the 4 weeks prior to screening and randomization were screened for inclusion.
405 adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) were randomized into this double-blind, multicenter study, and 403 received study medication. Patients were recruited to 47 study centers in Bulgaria, Czech Republic, Germany, Poland, Romania and the United Kingdom.
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| ID | Title | Description |
|---|---|---|
| FG000 | RPL554 0.75 mg | Patients were randomized to receive 0.75 milligrams (mg) RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| FG001 | RPL554 1.5 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Mar 6, 2018 | Jan 23, 2019 |
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The nebuliser cup will be obscured to prevent the Investigator or outcomes assessor so the contents are not visible to the Investigator our outcomes assessor. The visual appearance of the study medication will not be discussed with the subject
| Placebo | Drug | Placebo solution |
|
| Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
| Mean Change From Baseline FEV1 to Average FEV1 (Over 12 Hours) at Day 1 and Week 4 | Average FEV1 over 12 hours was defined as the area under the curve from 0 to 12 hours post-dose (AUC[0-12]) of the FEV1 values collected during the visit under analysis (Day 1 or Week 4), divided by the length of the time interval of interest (in hours). The AUC was calculated using the trapezoidal rule. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. MMRM was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The LS mean change from baseline FEV1 to average FEV1 over 12 hours at Day 1 and at Week 4 is presented. | Baseline (pre-dose, Visit 2), up to 12 hours post-dose at Visit 2 (Day 1) and Visit 6 (Week 4). |
| Mean Change From Baseline in COPD Symptoms Using the Exacerbations of Chronic Pulmonary Disease Tool Patient-Reported Outcome (EXACT-PRO) Scoring at Week 4 | Patients completed an electronic diary (e-diary) once daily which used the 14-item EXACT-PRO instrument to assess COPD symptoms. The EXACT-PRO instrument contains 11 respiratory symptom questions that comprise the derivative Evaluating Respiratory Symptoms (E-RS) instrument that was used to measure the effect of treatment with RPL554 on the severity of COPD symptoms overall. The E-RS tool contains 3 subscales to assess breathlessness, cough/sputum and chest symptoms. In addition to the subscale scores, a total score for the E-RS part was obtained. The raw totals for the E-RS score and for each of the subscales were converted to a scale range of 0 to 100 (least symptomatic to most symptomatic). MMRM was used to model the change from baseline using baseline as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. Baseline was the last non-missing assessment taken prior to investigational product start date. | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
| Mean Change From Baseline in Breathlessness as Assessed Using the St George's Respiratory Questionnaire (SGRQ) at Week 4 | Patients completed the COPD specific SGRQ (SGRQ-C) consisting of 14 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicate a worse outcome. Baseline assessment was pre-dose at Visit 2. MMRM was used to model the change from baseline using baseline as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, patient as random effect. The LS mean change from baseline in the total, symptoms, activity and impact SGRQ-C scores are presented. | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
| Number of Patients With Treatment Emergent Adverse Events (TEAEs) | The number of patients with TEAEs for each the following categories are presented: any TEAE, any drug-related TEAE, any severe TEAE, any serious TEAE, serious drug-related TEAE, any TEAE leading to drug interruption, any TEAE leading to drug discontinuation, and any TEAE leading to death. All AEs which started after the first dose of investigational product.or started prior to first dose and worsened, based on the Investigator assessment of severity, on or after first dose were considered to be treatment-emergent. | Up to end of study (approximately 6 weeks) |
| Rousse |
| Bulgaria |
| Fifth MHAT - Sofia EAD | Sofia | Bulgaria |
| MHAT 'Lyulin', EAD | Sofia | Bulgaria |
| NMTH Tsar Boris III | Sofia | Bulgaria |
| UMHAT 'Alexandrovska' EAD | Sofia | Bulgaria |
| UMHAT 'Sveta Anna' AD | Sofia | Bulgaria |
| Medical Center Nov | Stara Zagora | Bulgaria |
| MediTrial s.r.o. | Jindřichův Hradec | Czechia |
| Plicni stredisko Teplice | Teplice | Czechia |
| Aerzte fuer Lungen- und | Berlin | Germany |
| Charite Campus Mitte | Berlin | Germany |
| emovis GmbH | Berlin | Germany |
| Studienpraxis Berlin | Berlin | Germany |
| IKF Pneumologie GmbH & Co. KG | Frankfurt | Germany |
| Praxis Dr. Keller | Frankfurt | Germany |
| Inamed GmbH | Gauting | Germany |
| PRI Pulmonary Research | Großhansdorf | Germany |
| Hamburger Institut fuer | Hamburg | Germany |
| Gemeinschaftspraxis Dres | Koblenz | Germany |
| POIS Leipzig GbR | Leipzig | Germany |
| SALVUS UG Centre for Clinial Trials | Leipzig | Germany |
| KLB Gesundheitsforschung | Lübeck | Germany |
| Pneumologie Odeonsplatz | Munich | Germany |
| Pneumologische Praxis Pasing | München | Germany |
| Ballenberger Freytag Wenisch | Neu-Isenburg | Germany |
| Dr. Christian Schlenska | Peine | Germany |
| CERMED | Bialystok | Poland |
| Indywidualna Specjalistyczna | Bialystok | Poland |
| KLIMED Marek Klimkiewicz | Bychawa | Poland |
| Silmedic sp. z o.o. | Katowice | Poland |
| Grazyna Pulka Specjalistyczny | Krakow | Poland |
| Malopolskie Centrum Alergologii | Krakow | Poland |
| Centrum Terapii Wspólczesnej | Lodz | Poland |
| Uniwersytecki Szpital Klin | Lodz | Poland |
| NZOZ Alergo-MEDSpecjalistyczna | Poznan | Poland |
| ETG Network Sp z o o | Skierniewice | Poland |
| Centrum Medyczne Pratia | Warsaw | Poland |
| Mazowieckie Centrum Medyczne | Warsaw | Poland |
| Centrum Badan Klinicznych | Wroclaw | Poland |
| Specjalistyczna Opieka | Wroclaw | Poland |
| S.C Angisan S.R.L | Bragadiru | Romania |
| S.C Clinica Pneumomedica S.R.L | Brasov | Romania |
| Fundatia Dr. Victor Babes | Bucharest | Romania |
| Spitalul Clinic de Urgenta | Bucharest | Romania |
| Spitalul Cl. Pneumoftiziologie | Cluj-Napoca | Romania |
| Spitalul CldePneumoftiziologie | Constanța | Romania |
| Spitalul CldePneumoftiziologie | Iași | Romania |
| Medicines Evaluation Unit | Manchester | United Kingdom |
Patients were randomized to receive 1.5 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks.
| FG002 | RPL554 3.0 mg | Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| FG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| FG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| Received Treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The baseline population consists of all randomized patients.
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| ID | Title | Description |
|---|---|---|
| BG000 | RPL554 0.75 mg | Patients were randomized to receive 0.75 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| BG001 | RPL554 1.5 mg | Patients were randomized to receive 1.5 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| BG002 | RPL554 3.0 mg | Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| BG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| BG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| BG005 | Total Title |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | Mean Change From Baseline in Peak FEV1 (Over 3 Hours) at Week 4 | Spirometry assessments were used to assess pulmonary function including the forced expiratory volume in 1 second (FEV1). Peak FEV1 at Week 4 was defined as the maximum post-dose value among the 30 minutes, 1, 2 and 3 hour assessments collected at Visit 6. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. A mixed model for repeated measures (MMRM) was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The least squares (LS) mean change from baseline FEV1 to peak FEV1 (as measured over 3 hours) at Week 4 is presented. | The full analysis set (FAS) consisted of all randomized patients, who received at least 1 dose of investigational product during the study and with at least 1 post-treatment efficacy data assessment. Data is presented for the number of patients with at least 1 on-treatment value who contributed to the model estimate. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline FEV1 to Morning Trough FEV1 at Week 4 | Morning trough FEV1 was defined as the last pre-dose value at Visit 6. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. MMRM was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The LS mean change from baseline FEV1 to morning trough FEV1 at Week 4 is presented. | The FAS consisted of all randomized patients, who received at least 1 dose of investigational product during the study and with at least 1 post-treatment efficacy data assessment. Data is presented for the number of patients with at least 1 on-treatment value who contributed to the model estimate. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline FEV1 to Average FEV1 (Over 12 Hours) at Day 1 and Week 4 | Average FEV1 over 12 hours was defined as the area under the curve from 0 to 12 hours post-dose (AUC[0-12]) of the FEV1 values collected during the visit under analysis (Day 1 or Week 4), divided by the length of the time interval of interest (in hours). The AUC was calculated using the trapezoidal rule. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. MMRM was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The LS mean change from baseline FEV1 to average FEV1 over 12 hours at Day 1 and at Week 4 is presented. | The FAS consisted of all randomized patients, who received at least 1 dose of investigational product during the study and with at least 1 post-treatment efficacy data assessment. Data is presented for the number of patients with at least 1 on-treatment value who contributed to the model estimate. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Baseline (pre-dose, Visit 2), up to 12 hours post-dose at Visit 2 (Day 1) and Visit 6 (Week 4). |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in COPD Symptoms Using the Exacerbations of Chronic Pulmonary Disease Tool Patient-Reported Outcome (EXACT-PRO) Scoring at Week 4 | Patients completed an electronic diary (e-diary) once daily which used the 14-item EXACT-PRO instrument to assess COPD symptoms. The EXACT-PRO instrument contains 11 respiratory symptom questions that comprise the derivative Evaluating Respiratory Symptoms (E-RS) instrument that was used to measure the effect of treatment with RPL554 on the severity of COPD symptoms overall. The E-RS tool contains 3 subscales to assess breathlessness, cough/sputum and chest symptoms. In addition to the subscale scores, a total score for the E-RS part was obtained. The raw totals for the E-RS score and for each of the subscales were converted to a scale range of 0 to 100 (least symptomatic to most symptomatic). MMRM was used to model the change from baseline using baseline as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. Baseline was the last non-missing assessment taken prior to investigational product start date. | The FAS consisted of all randomized patients, who received at least 1 dose of investigational product during the study and with at least 1 post-treatment efficacy data assessment. Data is presented for the number of patients with at least 1 on-treatment value who contributed to the model estimate. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
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| Secondary | Mean Change From Baseline in Breathlessness as Assessed Using the St George's Respiratory Questionnaire (SGRQ) at Week 4 | Patients completed the COPD specific SGRQ (SGRQ-C) consisting of 14 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicate a worse outcome. Baseline assessment was pre-dose at Visit 2. MMRM was used to model the change from baseline using baseline as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, patient as random effect. The LS mean change from baseline in the total, symptoms, activity and impact SGRQ-C scores are presented. | The FAS consisted of all randomized patients, who received at least 1 dose of investigational product during the study and with at least 1 post-treatment efficacy data assessment. Data is presented for the numbers of patients with at least 1 on-treatment value who contributed to the model estimate. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline (pre-dose, Visit 2) and Week 4 (Visit 6). |
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| Secondary | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | The number of patients with TEAEs for each the following categories are presented: any TEAE, any drug-related TEAE, any severe TEAE, any serious TEAE, serious drug-related TEAE, any TEAE leading to drug interruption, any TEAE leading to drug discontinuation, and any TEAE leading to death. All AEs which started after the first dose of investigational product.or started prior to first dose and worsened, based on the Investigator assessment of severity, on or after first dose were considered to be treatment-emergent. | The safety analysis set consisted of all patients who received at least 1 dose of investigational product during the study. | Posted | Number | Patients | Up to end of study (approximately 6 weeks) |
|
TEAEs were collected from the first dose of investigational product up to 2 weeks after the end of the study (Visit 6) (approximately 6 weeks).
The safety analysis set consisted of all patients who received at least 1 dose of investigational product during the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | RPL554 0.75 mg | Patients were randomized to receive 0.75 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. | 0 | 81 | 2 | 81 | 20 | 81 |
| EG001 | RPL554 1.5 mg | Patients were randomized to receive 1.5 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. | 1 | 81 | 2 | 81 | 25 | 81 |
| EG002 | RPL554 3.0 mg | Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. | 0 | 82 | 1 | 82 | 24 | 82 |
| EG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. | 1 | 80 | 1 | 80 | 19 | 80 |
| EG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. | 0 | 79 | 1 | 79 | 25 | 79 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Mitral valve incompetence | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Obstructive pancreatitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hepatic cirrhosis | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hepatic encephalopathy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Ventricular extrasystoles | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
The Principal Investigator and Institution may only publish their center study activities and/or study data with prior written approval of the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brian Maurer, Senior Clinical Operations Director | Verona Pharma | (914) 767-5037 | brian.maurer@veronapharma.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Apr 18, 2017 | Jan 28, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Placebo-corrected treatment effect: LS mean difference (RPL554 3.0 mg - Placebo). |
| MMRM |
| <0.001 |
| LS mean difference |
| 0.200 |
| 2-Sided |
| 95 |
| 0.131 |
| 0.270 |
| Other |
A fixed-sequence testing approach was used, starting with the highest dose versus placebo. If a statistically significant difference was found at the 2-sided alpha level of 5%, the testing proceeded to the next highest dose. |
| Placebo-corrected treatment effect: LS mean difference (RPL554 1.5 mg - Placebo). | MMRM | <0.001 | LS mean difference | 0.153 | 2-Sided | 95 | 0.083 | 0.222 | Other | A fixed-sequence testing approach was used, starting with the highest dose versus placebo. If a statistically significant difference was found at the 2-sided alpha level of 5%, the testing proceeded to the next highest dose. |
| Placebo-corrected treatment effect: LS mean difference (RPL554 0.75 mg - Placebo). | MMRM | <0.001 | LS mean difference | 0.146 | 2-Sided | 95 | 0.075 | 0.216 | Other | A fixed-sequence testing approach was used, starting with the highest dose versus placebo. If a statistically significant difference was found at the 2-sided alpha level of 5%, the testing proceeded to the next highest dose. |
Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
|
|
|
| OG002 | RPL554 3.0 mg | Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
|
|
|
| OG001 | RPL554 1.5 mg | Patients were randomized to receive 1.5 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG002 | RPL554 3.0 mg | Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
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| OG001 | RPL554 1.5 mg | Patients were randomized to receive 1.5 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG002 | RPL554 3.0 mg | Patients were randomized to receive 3.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
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| OG003 | RPL554 6.0 mg | Patients were randomized to receive 6.0 mg RPL554 administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
| OG004 | Placebo | Patients were randomized to receive placebo administered by jet nebulizer twice daily (morning and evening) for 4 weeks. |
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