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| Name | Class |
|---|---|
| IQVIA Pty Ltd | INDUSTRY |
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The purpose of this study is to investigate 5 doses of RPL554 and placebo, administered by dry powder inhaler (DPI), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
The study will consist of two parts. Part A is a parallel group, placebo-controlled single dose study to ascertain the Pharmacokinetics (PK) profile, safety and bronchodilator effect of RPL554 administered via dry powder inhaler (DPI). Five of the 6 treatment arms will be double-blind and one will be single-blind (due to the different number of capsules administered). Part B is a placebo-controlled, complete block cross-over, repeat dose study to assess the bronchodilator effect of repeat doses of RPL554 delivered via a DPI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: RPL554 | Active Comparator | Placebo controlled, parallel group single dose. Five of the 6 treatment arms will be double-blind and one will be single-blind |
|
| Part B: RPL554 | Active Comparator | Double-blind, placebo-controlled, complete block cross-over |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Part A: RPL554 | Drug | 1 dose of either 50mcg/100mcg/1500mcg/3000mcg/6000mcg or placebo via dry powder inhaler |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12) | RPL554 Plasma pharmacokinetics AUC0-12 (Area under the Curve) after single dose | Day 1 |
| Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC 0-t) | RPL554 Area under the curve at maximum concentration after a single dose | Day 1 |
| Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life) | RPL554 Plasma pharmacokinetics Half-life concentration after a single dose | Day 1 |
| Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) | Change from Baseline FEV1 to Peak FEV1 (over 4 hours) on Day 7 | Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Change From Baseline in Average FEV1 (Over 4 Hours) | Change from Baseline FEV1 to Average FEV1 (over 4 hours) After Single Dose | Day 1 |
| Part A: Change From Baseline in Average FEV1 (Over 12 Hours) |
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Inclusion Criteria:
Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
For males, not to donate sperm and either be sexually abstinent or use contraception as specified by the protocol. For females, be of non-childbearing potential or use a highly effective form of contraception
12-lead ECG with heart rate between 45 and 90 beats per minute, QTcF ≤450 msec for males, and ≤ 470 msec for females, QRS interval ≤120 msec and no clinically significant abnormality including morphology
Capable of complying with all study restrictions and procedures including ability to use the DPI correctly.
Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
COPD diagnosis for 1 year [prior to screening
Ability to perform acceptable and reproducible spirometry.
Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating the following:
Clinically stable COPD in the 4 weeks prior to Screening and during the period between Screening and Part A.
A chest X-ray showing no abnormalities, which are both clinically significant and unrelated to COPD.
Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
Current and former smokers with smoking history of ≥10 pack years. 14. Capable of withdrawing from long acting bronchodilators for the duration of the study, and short acting bronchodilators for 8 hours prior to dosing.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J Boscia, MD | Vitalink Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VitaLink Research -- Union | Union | South Carolina | 29379 | United States |
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Part A: 37 Patients randomized equally to receive a single dose of RPL554 (0.15, 0.5, 1.5, 3, or 6 mg) or matching placebo via dry powder inhaler (DPI). Patients were to continue to Part B after Part A is complete.
Part B: 35 Patients continued from Part A and randomly assigned to 1 of 10 treatment sequences in a crossover design (5 x 1-week treatment periods separated by 7-10 day washout). Each sequence included twice daily RPL554 (0.15, 0.5, 1.5, or 3 mg) or matching placebo via DPI.
37 subjects enrolled for Part A and anticipated to continue into Part B.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.15 mg/Part A | Part A: Single dose of RPL554 via DPI (double-blind). |
| FG001 | 0.50 mg/Part A | Part A: Single dose of RPL554 via DPI (double-blind). |
| FG002 | 1.5 mg/Part A | Part A: Single dose of RPL554 via DPI (double-blind). |
| FG003 | 3 mg/Part A | Part A: Single dose of RPL554 via DPI (double-blind). |
| FG004 | 6 mg/Part A | Part A: Single dose of RPL554 via DPI (single-blind). Part B: dose not used. |
| FG005 | Placebo/Part A | Part A: Single dose via DPI (double-blind). |
| FG006 | Seq. 1/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 1 = RPL554 .15 mg/1.5 mg/3.0 mg/.50 mg/Placebo. |
| FG007 | Seq. 2/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 2 = RPL554 .15 mg/3.0 mg/Placebo/.50 mg/1.5 mg. |
| FG008 | Seq. 3/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 3 = RPL554 .50 mg/3.0 mg/.15 mg/Placebo/1.5 mg. |
| FG009 | Seq. 4/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 4 = RPL554 .50 mg/.15 mg/1.5 mg/Placebo/3.0 mg. |
| FG010 | Seq. 5/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 5 = RPL554 1.5 mg/.50 mg/Placebo/3.0 mg/.15 mg. |
| FG011 | Seq. 6/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 6 = RPL554 1.5 mg/Placebo/.15 mg/3.0 mg/.50 mg. |
| FG012 | Seq. 7/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 7 = RPL554 3.0 mg/1.5 mg/.50 mg/.15 mg/Placebo. |
| FG013 | Seq. 8/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 8 = RPL554 3.0 mg/Placebo/1.5 mg/.15 mg/.50 mg. |
| FG014 | Seq. 9/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 9 = Placebo/.15 mg/.50 mg/1.5 mg/3.0 mg. |
| FG015 | Seq. 10/Part B | Part B: 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over. Seq 10 = Placebo/.50 mg/3.0 mg/1.5 mg/.15 mg. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A (R, PC, PG) Single Dose |
| |||||||||||||
| Part B (R, PC, CO) Twice Daily for 7 Day |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 0.15 mg | Single dose of RPL554 via DPI (double-blind) |
| BG001 | 0.50 mg | Single dose of RPL554 via DPI (double blind) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12) | RPL554 Plasma pharmacokinetics AUC0-12 (Area under the Curve) after single dose | Pharmacokinetic (PK) Analysis Set in Part A: all randomized patients who had blood sampling performed after the single dose of RPL554 and had evaluable PK parameter data. The PK Analysis Set included the 31 patients who received RPL554 in Part A but not the 6 patients in the placebo group. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 |
|
Part A: 24 hours. Part B: Approximately 70 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: 0.15 mg | Single dose of RPL554 via DPI (double-blind) | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block first degree | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Verona Pharma | Verona Pharma | +44 (0)203 283 4200 | info@veronapharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 12, 2019 | Aug 29, 2022 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 8, 2019 | Oct 12, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| Part B: RPL554 | Drug | Patients will receive 4 or 5 repeat dose treatments in crossover fashion - doses will be confirmed after Part A |
|
| Placebos | Drug | Part A: 1 dose of either 50ncg/100ncg/1500ncg/3000ncg/6000ncg or placebo via dry powder inhaler. Part B: Patients will receive 4 or 5 repeat dose treatments in crossover fashion - doses will be confirmed after Part A. |
|
Change from Baseline FEV1 to Average FEV1 (over 12 hours) After Single Dose
| Day 1 |
| Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) | Change from Baseline FEV1 to Peak FEV1 (over 4 hours) After Single Dose | Day 1 |
| Part A: Safety and Tolerability / Hematology Safety Assessments | number of patients with treatment-emergent hematology abnormal laboratory assessments | Day 1 |
| Part A: Safety and Tolerability / Blood Chemistry Safety Assessments | number of patients with treatment-emergent blood chemistry abnormal laboratory assessments | Day 1 |
| Part A: Safety and Tolerability / Urinalysis Safety Assessments | number of patients with treatment-emergent urinalysis abnormal laboratory assessments | Day 1 |
| Part A: Safety and Tolerability / Supine Vital Signs - Pulse Rate | Change from Baseline Pulse Rate to Peak Pulse Rate (over 4 hours) After Single Dose | Day 1 |
| Part A: Safety and Tolerability / Supine Vital Signs - Blood Pressure | number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg) (An increase from baseline of >=20 in systolic bp) | Day 1 |
| Part A: Safety and Tolerability / ECG - QTcF | number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec | Day 1 |
| Part A: Safety and Tolerability / ECG - Heart Rate | number of patients with treatment-emergent clinically significant abnormal ECG parameters, heart rate in bpm | Day 1 |
| Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) | Change from baseline in average FEV1 (over 4 hours) on Day 7 | Day 7 |
| Part B: Change From Baseline in Average FEV1 (Over 12 Hours) | Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 7 | Day 7 |
| Part B: Change From Baseline in Trough FEV1 | Change from Baseline FEV1 to Morning Trough FEV1 on Day 7 | Day 7 |
| Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) | Change from baseline FEV1 in peak FEV1 (over 4 hours) after first dose | Day 1 |
| Part B: Change From Baseline in Average FEV1 (Over 4 Hours) | Change from baseline FEV1 in average FEV1 (over 4 hours) on Day 1 | Day 1 |
| Part B: Change From Baseline in Average FEV1 (Over 12 Hours) | Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 1 | Day 1 |
| Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action) | Determination of onset of action (>10% increase in FEV1 from pre- to post-first dose, censored at 120 minutes) on Day 1 | Day 1 |
| Part B: Safety and Tolerability / Hematology Safety Assessments | number of patients with treatment-emergent hematology abnormal laboratory assessments (changes from normal at baseline to low or high on Day 7 or at the end of study in >3 patients in each treatment group). | Day 7 |
| Part B: Safety and Tolerability / Blood Chemistry Safety Assessments | number of patients with treatment-emergent blood chemistry abnormal laboratory assessments (changes from normal at baseline to low or high on Day 7 in each treatment group). | Day 7 |
| Part B: Safety and Tolerability / Urinalysis Safety Assessments | number of patients with treatment-emergent urinalysis abnormal laboratory assessments | Day 7 |
| Part B: Safety and Tolerability / ECG - QTcF | number of patients with treatment-emergent clinically significant abnormal ECG parameters, QTcF in msec | Day 7 |
| Part B: Safety and Tolerability / ECG - Heart Rate | number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm | Day 7 |
| Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate | number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm) An increase from baseline of >=20 | Day 7 |
| Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure | number of patients with treatment-emergent abnormal vital signs (systolic blood pressure in mm Hg) (An increase from baseline of >=20) | Day 7 |
| Part B: Change From Baseline in Peak Pulse Rate (Day 1) | Change from baseline in peak pulse after first dose on Day 1 | Day 1 |
| Part B: Change From Baseline in Peak Pulse Rate (Day 7) | Change from baseline in peak pulse after morning dosing on Day 7 | Day 7 |
| Part B: RPL554 Plasma Pharmacokinetic Parameter (Tmax) | RPL554 steady-state PK (tmax) after morning dose on Day 7 | Day 7 |
| Part B: RPL554 Plasma Pharmacokinetic Parameter (Cmax) | RPL554 steady-state PK (Cmax and accumulation ratio) after morning dose on Day 7 | Day 7 |
| Part B: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12h) | RPL554 steady-state PK (AUC0-12h and accumulation ratio) after morning dose on Day 7 | Day 7 |
| COMPLETED |
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| NOT COMPLETED |
|
| BG002 | 1.5 mg | Single dose of RPL554 via DPI (double blind) |
| BG003 | 3 mg | Single dose of RPL554 via DPI (double blind) |
| BG004 | 6 mg | Single dose of RPL554 via DPI (single blind) |
| BG005 | Placebo | Single dose via DPI (double blind) |
| BG006 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG002 | 1.5 mg | Single dose of RPL554 via DPI (double blind) |
| OG003 | 3 mg | Single dose of RPL554 via DPI (double blind) |
| OG004 | 6 mg | Single dose of RPL554 via DPI (single blind) |
|
|
| Primary | Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC 0-t) | RPL554 Area under the curve at maximum concentration after a single dose | Pharmacokinetic (PK) Analysis Set in Part A: all randomized patients who had blood sampling performed after the single dose of RPL554 and had evaluable PK parameter data. The PK Analysis Set included the 31 patients who received RPL554 in Part A but not the 6 patients in the placebo group. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 |
|
|
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| Primary | Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life) | RPL554 Plasma pharmacokinetics Half-life concentration after a single dose | Pharmacokinetic (PK) Analysis Set in Part A: all randomized patients who had blood sampling performed after the single dose of RPL554 and had evaluable PK parameter data. The PK Analysis Set included the 31 patients who received RPL554 in Part A but not the 6 patients in the placebo group. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Day 1 |
|
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| Primary | Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) | Change from Baseline FEV1 to Peak FEV1 (over 4 hours) on Day 7 | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 7 |
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| Secondary | Part A: Change From Baseline in Average FEV1 (Over 4 Hours) | Change from Baseline FEV1 to Average FEV1 (over 4 hours) After Single Dose | Full Analysis Set (FAS) in Part A: all randomized patients with sufficient data collected after intake of study medication to compute the PD parameters (FEV1 measurements pre dose and at least 1 post-baseline). All 37 patients randomized into Part A were included in the FAS. | Posted | Mean | Standard Deviation | L | Day 1 |
|
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| Secondary | Part A: Change From Baseline in Average FEV1 (Over 12 Hours) | Change from Baseline FEV1 to Average FEV1 (over 12 hours) After Single Dose | Full Analysis Set (FAS) in Part A: all randomized patients with sufficient data collected after intake of study medication to compute the PD parameters (FEV1 measurements pre dose and at least 1 post-baseline). All 37 patients randomized into Part A were included in the FAS. | Posted | Mean | Standard Deviation | L | Day 1 |
|
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| Secondary | Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) | Change from Baseline FEV1 to Peak FEV1 (over 4 hours) After Single Dose | Full Analysis Set (FAS) in Part A: all randomized patients with sufficient data collected after intake of study medication to compute the PD parameters (FEV1 measurements pre dose and at least 1 post-baseline). All 37 patients randomized into Part A were included in the FAS. | Posted | Mean | Standard Deviation | L | Day 1 |
|
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| Secondary | Part A: Safety and Tolerability / Hematology Safety Assessments | number of patients with treatment-emergent hematology abnormal laboratory assessments | Not Posted | Day 1 | Participants |
| Secondary | Part A: Safety and Tolerability / Blood Chemistry Safety Assessments | number of patients with treatment-emergent blood chemistry abnormal laboratory assessments | Not Posted | Day 1 | Participants |
| Secondary | Part A: Safety and Tolerability / Urinalysis Safety Assessments | number of patients with treatment-emergent urinalysis abnormal laboratory assessments | Not Posted | Day 1 | Participants |
| Secondary | Part A: Safety and Tolerability / Supine Vital Signs - Pulse Rate | Change from Baseline Pulse Rate to Peak Pulse Rate (over 4 hours) After Single Dose | Not Posted | Day 1 | Participants |
| Secondary | Part A: Safety and Tolerability / Supine Vital Signs - Blood Pressure | number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg) (An increase from baseline of >=20 in systolic bp) | Not Posted | Day 1 | Participants |
| Secondary | Part A: Safety and Tolerability / ECG - QTcF | number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec | Not Posted | Day 1 | Participants |
| Secondary | Part A: Safety and Tolerability / ECG - Heart Rate | number of patients with treatment-emergent clinically significant abnormal ECG parameters, heart rate in bpm | Not Posted | Day 1 | Participants |
| Secondary | Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) | Change from baseline in average FEV1 (over 4 hours) on Day 7 | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 7 |
|
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|
|
| Secondary | Part B: Change From Baseline in Average FEV1 (Over 12 Hours) | Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 7 | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 7 |
|
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| Secondary | Part B: Change From Baseline in Trough FEV1 | Change from Baseline FEV1 to Morning Trough FEV1 on Day 7 | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 7 |
|
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| Secondary | Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) | Change from baseline FEV1 in peak FEV1 (over 4 hours) after first dose | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 1 |
|
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|
|
| Secondary | Part B: Change From Baseline in Average FEV1 (Over 4 Hours) | Change from baseline FEV1 in average FEV1 (over 4 hours) on Day 1 | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 1 |
|
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|
|
| Secondary | Part B: Change From Baseline in Average FEV1 (Over 12 Hours) | Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 1 | All efficacy analyses were carried out using the Full Analysis Set (FAS) in Part B: all randomized patients with sufficient data (pre-dose and at least 1 post-dose assessment of spirometry) collected after intake of study medication to compute the PD parameters (FEV1, FRC measurements) on at least 2 treatment periods in Part B. The FAS comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Mean | Standard Deviation | L | Day 1 |
|
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|
|
| Secondary | Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action) | Determination of onset of action (>10% increase in FEV1 from pre- to post-first dose, censored at 120 minutes) on Day 1 | Pharmacokinetic (PK) Analysis Set in Part B: all randomized patients who had blood sampling performed after at least 1 dose of RPL554 in Part B and with data sufficient to calculate PK parameters. The PK analysis set comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Median | Full Range | mins | Day 1 |
|
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| Secondary | Part B: Safety and Tolerability / Hematology Safety Assessments | number of patients with treatment-emergent hematology abnormal laboratory assessments (changes from normal at baseline to low or high on Day 7 or at the end of study in >3 patients in each treatment group). | Not Posted | Day 7 | Participants |
| Secondary | Part B: Safety and Tolerability / Blood Chemistry Safety Assessments | number of patients with treatment-emergent blood chemistry abnormal laboratory assessments (changes from normal at baseline to low or high on Day 7 in each treatment group). | Not Posted | Day 7 | Participants |
| Secondary | Part B: Safety and Tolerability / Urinalysis Safety Assessments | number of patients with treatment-emergent urinalysis abnormal laboratory assessments | Not Posted | Day 7 | Participants |
| Secondary | Part B: Safety and Tolerability / ECG - QTcF | number of patients with treatment-emergent clinically significant abnormal ECG parameters, QTcF in msec | Not Posted | Day 7 | Participants |
| Secondary | Part B: Safety and Tolerability / ECG - Heart Rate | number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm | Not Posted | Day 7 | Participants |
| Secondary | Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate | number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm) An increase from baseline of >=20 | Not Posted | Day 7 | Participants |
| Secondary | Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure | number of patients with treatment-emergent abnormal vital signs (systolic blood pressure in mm Hg) (An increase from baseline of >=20) | Not Posted | Day 7 | Participants |
| Secondary | Part B: Change From Baseline in Peak Pulse Rate (Day 1) | Change from baseline in peak pulse after first dose on Day 1 | Not Posted | Day 1 | Participants |
| Secondary | Part B: Change From Baseline in Peak Pulse Rate (Day 7) | Change from baseline in peak pulse after morning dosing on Day 7 | Not Posted | Day 7 | Participants |
| Secondary | Part B: RPL554 Plasma Pharmacokinetic Parameter (Tmax) | RPL554 steady-state PK (tmax) after morning dose on Day 7 | Pharmacokinetic (PK) Analysis Set in Part B: all randomized patients who had blood sampling performed after at least 1 dose of RPL554 in Part B and with data sufficient to calculate PK parameters. The PK analysis set comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Median | Full Range | h | Day 7 |
|
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| Secondary | Part B: RPL554 Plasma Pharmacokinetic Parameter (Cmax) | RPL554 steady-state PK (Cmax and accumulation ratio) after morning dose on Day 7 | Pharmacokinetic (PK) Analysis Set in Part B: all randomized patients who had blood sampling performed after at least 1 dose of RPL554 in Part B and with data sufficient to calculate PK parameters. The PK analysis set comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Day 7 |
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|
|
| Secondary | Part B: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12h) | RPL554 steady-state PK (AUC0-12h and accumulation ratio) after morning dose on Day 7 | Pharmacokinetic (PK) Analysis Set in Part B: all randomized patients who had blood sampling performed after at least 1 dose of RPL554 in Part B and with data sufficient to calculate PK parameters. The PK analysis set comprised: RPL554 0.15 mg (N=34); RPL554 0.5 mg (N=33); RPL554 1.5 mg (N=32); RPL554 3 mg (N=33); Placebo (N=32). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 7 |
|
|
|
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Part A: 0.50 mg | Single dose of RPL554 via DPI (double blind) | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Part A: 1.5 mg | Single dose of RPL554 via DPI (double blind) | 0 | 7 | 0 | 7 | 1 | 7 |
| EG003 | Part A: 3 mg | Single dose of RPL554 via DPI (double blind) | 0 | 6 | 0 | 6 | 0 | 6 |
| EG004 | Part A: 6 mg | Single dose of RPL554 via DPI (single blind) | 0 | 6 | 0 | 6 | 0 | 6 |
| EG005 | Part A: Placebo | Single dose of placebo via DPI (double blind) | 0 | 6 | 0 | 6 | 0 | 6 |
| EG006 | Part B: 0.15 mg | 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over | 0 | 35 | 0 | 35 | 3 | 35 |
| EG007 | Part B: 0.50 mg | 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over | 0 | 33 | 0 | 33 | 9 | 33 |
| EG008 | Part B: 1.5 mg | 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over | 0 | 32 | 0 | 32 | 4 | 32 |
| EG009 | Part B: 3 mg | 7 day, twice daily dose of RPL554 via DPI (double-blind) complete block, cross-over | 0 | 33 | 0 | 33 | 4 | 33 |
| EG010 | Part B: Placebo | 7 day, twice daily dose of placebo via DPI (double-blind) complete block, cross-over | 0 | 32 | 0 | 32 | 5 | 32 |
| Hypertension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 21.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Eye contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
|
Not provided
Not provided
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Contrast Ratio |
| 1.134 |
| 2-Sided |
| 95 |
| 1.088 |
| 1.181 |
| Other |
| ANCOVA | <0.0001 | Contrast Ratio | 1.134 | 2-Sided | 95 | 1.089 | 1.181 | Other |
| ANCOVA | 0.0001 | Contrast Ratio | 1.084 | 2-Sided | 95 | 1.041 | 1.128 | Other |
| Contrast Ratio |
| 1.228 |
| 2-Sided |
| 95 |
| 1.104 |
| 1.365 |
| Other |
| ANCOVA | 0.0012 | Contrast Ratio | 1.196 | 2-Sided | 95 | 1.080 | 1.326 | Other |
| ANCOVA | 0.0348 | Contrast Ratio | 1.121 | 2-Sided | 95 | 1.009 | 1.246 | Other |
| ANCOVA | 0.3106 | Contrast Ratio | 1.055 | 2-Sided | 95 | 0.949 | 1.172 | Other |
| Contrast Ratio |
| 1.200 |
| 2-Sided |
| 95 |
| 1.064 |
| 1.353 |
| Other |
| ANCOVA | 0.0108 | Contrast Ratio | 1.167 | 2-Sided | 95 | 1.039 | 1.311 | Other |
| ANCOVA | 0.1641 | Contrast Ratio | 1.087 | 2-Sided | 95 | 0.965 | 1.225 | Other |
| Contrast Ratio |
| 1.231 |
| 2-Sided |
| 95 |
| 1.104 |
| 1.372 |
| Other |
| ANCOVA | 0.0022 | Contrast Ratio | 1.188 | 2-Sided | 95 | 1.070 | 1.320 | Other |
| ANCOVA | 0.0658 | Contrast Ratio | 1.106 | 2-Sided | 95 | 0.993 | 1.233 | Other |
| Contrast Ratio |
| 1.140 |
| 2-Sided |
| 95 |
| 1.092 |
| 1.190 |
| Other |
| ANCOVA | <0.0001 | Contrast Ratio | 1.131 | 2-Sided | 95 | 1.084 | 1.180 | Other |
| ANCOVA | 0.0004 | Contrast Ratio | 1.080 | 2-Sided | 95 | 1.036 | 1.126 | Other |
| Contrast Ratio |
| 1.078 |
| 2-Sided |
| 95 |
| 1.035 |
| 1.122 |
| Other |
| ANCOVA | 0.0002 | Contrast Ratio | 1.081 | 2-Sided | 95 | 1.039 | 1.125 | Other |
| ANCOVA | 0.0437 | Contrast Ratio | 1.041 | 2-Sided | 95 | 1.001 | 1.083 | Other |
| Contrast Ratio |
| 1.083 |
| 2-Sided |
| 95 |
| 1.034 |
| 1.135 |
| Other |
| ANCOVA | 0.0002 | Contrast Ratio | 1.096 | 2-Sided | 95 | 1.047 | 1.149 | Other |
| ANCOVA | 0.0971 | Contrast Ratio | 1.039 | 2-Sided | 95 | 0.993 | 1.088 | Other |
| Contrast Ratio |
| 1.148 |
| 2-Sided |
| 95 |
| 1.109 |
| 1.189 |
| Other |
| ANCOVA | <0.0001 | Contrast Ratio | 1.099 | 2-Sided | 95 | 1.062 | 1.137 | Other |
| ANCOVA | <0.0001 | Contrast Ratio | 1.088 | 2-Sided | 95 | 1.052 | 1.126 | Other |
| Contrast Ratio |
| 1.146 |
| 2-Sided |
| 95 |
| 1.109 |
| 1.185 |
| Other |
| ANCOVA | <0.0001 | Contrast Ratio | 1.107 | 2-Sided | 95 | 1.071 | 1.144 | Other |
| ANCOVA | <0.0001 | Contrast Ratio | 1.094 | 2-Sided | 95 | 1.059 | 1.130 | Other |
| Contrast Ratio |
| 1.078 |
| 2-Sided |
| 95 |
| 1.042 |
| 1.116 |
| Other |
| ANCOVA | 0.0002 | Contrast Ratio | 1.067 | 2-Sided | 95 | 1.032 | 1.104 | Other |
| ANCOVA | 0.0066 | Contrast Ratio | 1.048 | 2-Sided | 95 | 1.013 | 1.084 | Other |