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CompletedNCT04091360Updated Sep 21, 2022Results posted

A Study of RPL554 Drug Administered by Metered Dose Inhaler to Treat Chronic Obstructive Pulmonary Disease

A Phase 2 interventional study of Part A: RPL554 and Placebos in COPD, sponsored by Verona Pharma plc. Completed at 2 sites in United Kingdom. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-09-21.

Sponsored by Verona Pharma plc · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
40 Years to 80 Years
Sex
All
01

Study summary

The purpose of this study is to investigate 5 doses of RPL554 and placebo, administered by pressurized metered dose inhaler (pMDI), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Read the detailed description

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 a single dose of RPL554 administered via pMDI. 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 7-day placebo-controlled, complete block cross-over, repeat dose study to assess the bronchodilator effect of repeat doses of RPL554 delivered via pMDI.

02

Conditions studied

  • COPD

Keywords

  • COPD
  • Adults
  • Phase II
  • RPL554
  • Ensifentrine
03

In context

Lead sponsor

Verona Pharma plc is the lead sponsor of 13 studies on the registry; none are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male and female patients with moderate to severe COPD, with a post bronchodilator FEV1 of 40 to 80% of predicted and FEV1/FVC ratio of ≤0.70.
  • They must have a baseline increase in FEV1 of >150 mL following four puffs of salbutamol.
  • They must have at least a 10 pack-year smoking history, and may be either a current or former smoker.

Exclusion criteria

Exclusion Criteria:

  • Patients must be clinically stable without recent COPD exacerbations or hospitalisations.
  • They must not have uncontrolled disease or chronic heart failure.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    RPL554 100 mcg

    Part A: Patients receive 1 dose of either RPL554 100mcg via metered dose inhaler. Part B: not applicable

    Drug: Part A: RPL554 · Drug: Placebos

  • Experimental
    RPL554 300 mcg

    Part A: Patients receive 1 dose of RPL554 300mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 300mcg via metered dose inhaler in crossover fashion.

    Drug: Part A: RPL554 · Drug: Placebos · Drug: Part B: RPL554

  • Experimental
    RPL554 1000 mcg

    Part A: Patients receive 1 dose of RPL554 1000mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 3000mcg via metered dose inhaler in crossover fashion.

    Drug: Part A: RPL554 · Drug: Placebos · Drug: Part B: RPL554

  • Experimental
    RPL554 3000 mcg

    Part A: Patients receive 1 dose of either RPL554 3000mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 3000mcg via metered dose inhaler in crossover fashion.

    Drug: Part A: RPL554 · Drug: Placebos · Drug: Part B: RPL554

  • Experimental
    RPL554 6000 mcg

    Part A: Patients receive 1 dose of either RPL554 6000mcg via metered dose inhaler. Part B: not applicable

    Drug: Part A: RPL554 · Drug: Placebos

  • Placebo comparator
    RPL554 Placebo

    Part A: Patients receive 1 dose of RPL554 placebo via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 placebo via metered dose inhaler in crossover fashion.

    Drug: Part A: RPL554 · Drug: Placebos

Interventions

  • DrugPart A: RPL554

    Single dose RPL554 via metered dose inhaler.

    Also known as: Part A

  • DrugPlacebos

    Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.

  • DrugPart B: RPL554

    Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days.

    Also known as: Part B

06

What researchers measure

Primary outcomes

  1. Part A: Pharmacokinetic Parameter AUC0-12

    Area under the curve from 0 to 12 hours after single dose drug administration.

    Time frame: Day 1

  2. Part A: Pharmacokinetic Parameter Cmax

    Pharmacokinetic Parameter Cmax after a Single Dose

    Time frame: Day 1

  3. Part A: Pharmacokinetic Parameter AUC0-t

    Area under the curve at maximum concentration 0-24 hrs after single dose drug administration

    Time frame: Day 1

  4. Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)

    RPL554 Plasma Pharmacokinetics concentration after single dose

    Time frame: Day 1

  5. Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7

    Change from Baseline FEV1 to Peak FEV1 (over 4 hours) after morning dosing on Day 7

    Time frame: Day 7

Secondary outcomes

  1. Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose

    Change from Baseline FEV1 to Peak FEV1 (over 4 hours) After Single Dose

    Time frame: Day 1

  2. Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose

    Change from Baseline FEV1 to Average FEV1 (over 4 hours) After Single Dose

    Time frame: Day 1

  3. Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose

    Change from Baseline FEV1 to Average FEV1 (over 12 hours) After Single Dose

    Time frame: Day 1

  4. Part A: Safety and Tolerability / Hematology Safety Assessments

    Number of patients with treatment-emergent hematology abnormal laboratory assessments

    Time frame: 1 day

  5. Part A: Safety and Tolerability / Blood Chemistry Safety Assessments: Number of Patients With Treatment-emergent Blood Chemistry Abnormal Laboratory Assessments

    Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments

    Time frame: 1 day

  6. Part A: Safety and Tolerability / Urinalysis Safety Assessments: Number of Patients With Treatment-emergent Urinalysis Abnormal Laboratory Assessments

    Number of patients with treatment-emergent urinalysis abnormal laboratory assessments

    Time frame: 1 day

  7. Part A: Safety and Tolerability / Supine Vitals Signs - Pulse Rate

    Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm)

    Time frame: Start of treatment to day 1

  8. Part A: Safety and Tolerability / Supine Vitals Signs - Blood Pressure

    Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg)

    Time frame: Start of treatment to day 1

  9. Part A: Safety and Tolerability / ECG - QTcF

    Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec

    Time frame: Start of treatment to day 1

  10. Part A: Safety and Tolerability / ECG - Heart Rate

    Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm

    Time frame: Start of treatment to day 1

  11. Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days

    Change from baseline in average FEV1 (over 4 hours) on Day 7 after morning dose

    Time frame: Day 7

  12. Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days

    Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 7 after morning dose

    Time frame: Day 7

  13. Part B: Change From Baseline in Trough FEV1 After 7 Days

    Change from Baseline FEV1 to Morning Trough FEV1 on Day 7 after morning dose

    Time frame: Day 7

  14. Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose

    Change from baseline FEV1 in peak FEV1 (over 4 hours) after first dose

    Time frame: Day 1

  15. Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose

    Change from baseline FEV1 in average FEV1 (over 4 hours) on Day 1

    Time frame: Day 1

  16. Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose

    Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 1

    Time frame: Day 1

  17. 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

    Time frame: Day 1

  18. Part B: Safety and Tolerability / Hematology Safety Assessments

    Number of patients with treatment-emergent hematology abnormal laboratory assessments

    Time frame: 1 day

  19. Part B: Safety and Tolerability / Blood Chemistry Safety Assessments

    Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments

    Time frame: 1 day

  20. Part B: Safety and Tolerability / Urinalysis Safety Assessments

    Number of patients with treatment-emergent urinalysis abnormal laboratory assessments

    Time frame: 1 day

  21. Part B: Safety and Tolerability / Supine Vital Signs - Pulse Rate

    Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm)

    Time frame: Start of treatment to day 1

  22. Part B: Safety and Tolerability / Supine Vital Signs - Blood Pressure

    Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg)

    Time frame: Start of treatment to day 1

  23. Part B: Safety and Tolerability / ECG - QTcF

    Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec

    Time frame: Start of treatment to day 70

  24. Part B: Safety and Tolerability / ECG - Heart Rate

    Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm

    Time frame: Start of treatment to day 70

07

Results

Posted Jul 25, 2022

Participant flow

40 subjects enrolled for Part A and eligible to continue into Part B.

Part A (R, PC, PG) Single Dose
Participant flow — Part A (R, PC, PG) Single Dose
Milestone0.10 mg/Part A0.30 mg/Part A1 mg/Part A3 mg/Part A6 mg/Part APlacebo/Part ASeq 1/Part BSeq 2/Part BSeq 3/Part BSeq 4/Part B
Started6767770000
Completed6767770000
Not completed0000000000
Part B (R, PC, XO) Twice Daily for 7 Day
Participant flow — Part B (R, PC, XO) Twice Daily for 7 Day
Milestone0.10 mg/Part A0.30 mg/Part A1 mg/Part A3 mg/Part A6 mg/Part APlacebo/Part ASeq 1/Part BSeq 2/Part BSeq 3/Part BSeq 4/Part B
Started0000008776
Completed0000006664
Not completed0000002112
Withdrew: Adverse event0000000011
Withdrew: Physician decision0000001100
Withdrew: Withdrawal by subject0000001001

Outcome measures

PrimaryPart A: Pharmacokinetic Parameter AUC0-12

Area under the curve from 0 to 12 hours after single dose drug administration.

Time frame:
Day 1
Reported as:
Mean · h*pg/mL
Part A: Pharmacokinetic Parameter AUC0-12
h*pg/mL0.10 mg0.30 mg1 mg3 mg6 mg
Part A: Pharmacokinetic Parameter AUC0-12175 ± 96.7611 ± 1831550 ± 4435860 ± 31209360 ± 8100
PrimaryPart A: Pharmacokinetic Parameter Cmax

Pharmacokinetic Parameter Cmax after a Single Dose

Time frame:
Day 1
Reported as:
Mean · pg/mL
Part A: Pharmacokinetic Parameter Cmax
pg/mL0.10 mg0.30 mg1 mg3 mg6 mg
Part A: Pharmacokinetic Parameter Cmax39.4 ± 16.4138 ± 40.9467 ± 57.81520 ± 10502360 ± 1430
PrimaryPart A: Pharmacokinetic Parameter AUC0-t

Area under the curve at maximum concentration 0-24 hrs after single dose drug administration

Time frame:
Day 1
Reported as:
Mean · h*pg/mL
Part A: Pharmacokinetic Parameter AUC0-t
h*pg/mL0.10 mg0.30 mg1 mg3 mg6 mg
Part A: Pharmacokinetic Parameter AUC0-t208 ± 119692 ± 2291680 ± 5596800 ± 377010800 ± 10100
PrimaryPart A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)

RPL554 Plasma Pharmacokinetics concentration after single dose

Time frame:
Day 1
Reported as:
Mean · h
Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)
h0.10 mg0.30 mg1 mg3 mg6 mg
Part A: RPL554 Plasma Pharmacokinetic Parameter (Half-life)6.31 ± 5.185.32 ± 3.363.47 ± 1.445.62 ± 1.74.44 ± 2.03
PrimaryPart B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7

Change from Baseline FEV1 to Peak FEV1 (over 4 hours) after morning dosing on Day 7

Time frame:
Day 7
Reported as:
Mean · L
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 7
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) on Day 70.189 ± 0.16240.261 ± 0.15970.310 ± 0.1511-0.016 ± 0.1485
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.221 · 95% CI 1.163 to 1.281
  • 1 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.203 · 95% CI 1.146 to 1.263
  • 0.30 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.139 · 95% CI 1.085 to 1.195
SecondaryPart A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose

Change from Baseline FEV1 to Peak FEV1 (over 4 hours) After Single Dose

Time frame:
Day 1
Reported as:
Mean · L
Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose
L0.10 mg0.30 mg1 mg3 mg6 mgPlacebo
Part A: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1 Dose0.133 ± 0.11440.264 ± 0.10120.255 ± 0.09940.332 ± 0.20950.477 ± 0.14690.086 ± 0.0694
Statistical analysis
  • 6 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.253 · 95% CI 1.151 to 1.363
  • 3 mg vs Placebo · ANCOVA · p = 0.0022 · Geomean ratio: 1.146 · 95% CI 1.054 to 1.246
  • 1 mg vs Placebo · ANCOVA · p = 0.0295 · Geomean ratio: 1.102 · 95% CI 1.010 to 1.202
  • 0.30 mg vs Placebo · ANCOVA · p = 0.0098 · Geomean ratio: 1.129 · 95% CI 1.032 to 1.235
  • 0.10 mg vs Placebo · ANCOVA · p = 0.54 · Geomean ratio: 1.028 · 95% CI 0.939 to 1.125
SecondaryPart A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose

Change from Baseline FEV1 to Average FEV1 (over 4 hours) After Single Dose

Time frame:
Day 1
Reported as:
Mean · L
Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose
L0.10 mg0.30 mg1 mg3 mg6 mgPlacebo
Part A: Change From Baseline in Average FEV1 (Over 4 Hours) After 1 Dose0.058 ± 0.08890.161 ± 0.06500.153 ± 0.06530.240 ± 0.16770.334 ± 0.1147-0.011 ± 0.0805
Statistical analysis
  • 6 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.228 · 95% CI 1.142 to 1.319
  • 3 mg vs Placebo · ANCOVA · p = 0.0002 · Geomean ratio: 1.155 · 95% CI 1.075 to 1.240
  • 1 mg vs Placebo · ANCOVA · p = 0.0129 · Geomean ratio: 1.100 · 95% CI 1.022 to 1.184
  • 0.30 mg vs Placebo · ANCOVA · p = 0.0079 · Geomean ratio: 1.112 · 95% CI 1.030 to 1.201
  • 0.10 mg vs Placebo · ANCOVA · p = 0.39 · Geomean ratio: 1.033 · 95% CI 0.957 to 1.116
SecondaryPart A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose

Change from Baseline FEV1 to Average FEV1 (over 12 hours) After Single Dose

Time frame:
Day 1
Reported as:
Mean · L
Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose
L0.10 mg0.30 mg1 mg3 mg6 mgPlacebo
Part A: Change From Baseline in Average FEV1 (Over 12 Hours) After 1 Dose0.018 ± 0.06430.061 ± 0.04290.010 ± 0.04080.121 ± 0.13210.190 ± 0.1053-0.031 ± 0.0740
Statistical analysis
  • 6 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.137 · 95% CI 1.073 to 1.204
  • 3 mg vs Placebo · ANCOVA · p = 0.0041 · Geomean ratio: 1.091 · 95% CI 1.030 to 1.155
  • 1 mg vs Placebo · ANCOVA · p = 0.53 · Geomean ratio: 1.019 · 95% CI 0.960 to 1.081
SecondaryPart A: Safety and Tolerability / Hematology Safety Assessments

Number of patients with treatment-emergent hematology abnormal laboratory assessments

Time frame:
1 day

Results for this outcome have not been posted.

SecondaryPart A: Safety and Tolerability / Blood Chemistry Safety Assessments: Number of Patients With Treatment-emergent Blood Chemistry Abnormal Laboratory Assessments

Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments

Time frame:
1 day

Results for this outcome have not been posted.

SecondaryPart A: Safety and Tolerability / Urinalysis Safety Assessments: Number of Patients With Treatment-emergent Urinalysis Abnormal Laboratory Assessments

Number of patients with treatment-emergent urinalysis abnormal laboratory assessments

Time frame:
1 day

Results for this outcome have not been posted.

SecondaryPart A: Safety and Tolerability / Supine Vitals Signs - Pulse Rate

Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm)

Time frame:
Start of treatment to day 1

Results for this outcome have not been posted.

SecondaryPart A: Safety and Tolerability / Supine Vitals Signs - Blood Pressure

Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg)

Time frame:
Start of treatment to day 1

Results for this outcome have not been posted.

SecondaryPart A: Safety and Tolerability / ECG - QTcF

Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec

Time frame:
Start of treatment to day 1

Results for this outcome have not been posted.

SecondaryPart A: Safety and Tolerability / ECG - Heart Rate

Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm

Time frame:
Start of treatment to day 1

Results for this outcome have not been posted.

SecondaryPart B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days

Change from baseline in average FEV1 (over 4 hours) on Day 7 after morning dose

Time frame:
Day 7
Reported as:
Mean · L
Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Average FEV1 (Over 4 Hrs) After 7 Days0.083 ± 0.12230.161 ± 0.16860.206 ± 0.1470-0.095 ± 0.1702
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.210 · 95% CI 1.153 to 1.270
  • 1 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.193 · 95% CI 1.136 to 1.252
  • 0.30 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.124 · 95% CI 1.071 to 1.179
SecondaryPart B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days

Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 7 after morning dose

Time frame:
Day 7
Reported as:
Mean · L
Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 7 Days0.008 ± 0.14210.075 ± 0.14720.085 ± 0.1411-0.112 ± 0.1662
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.139 · 95% CI 1.087 to 1.194
  • 1 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.142 · 95% CI 1.089 to 1.197
  • 0.30 mg vs Placebo · ANCOVA · p = 0.0018 · Geomean ratio: 1.080 · 95% CI 1.031 to 1.132
SecondaryPart B: Change From Baseline in Trough FEV1 After 7 Days

Change from Baseline FEV1 to Morning Trough FEV1 on Day 7 after morning dose

Time frame:
Day 7
Reported as:
Mean · L
Part B: Change From Baseline in Trough FEV1 After 7 Days
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Trough FEV1 After 7 Days-0.051 ± 0.1254-0.017 ± 0.17830.013 ± 0.1631-0.097 ± 0.1389
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = 0.0066 · Geomean ratio: 1.080 · 95% CI 1.022 to 1.140
  • 1 mg vs Placebo · ANCOVA · p = 0.0115 · Geomean ratio: 1.074 · 95% CI 1.017 to 1.134
  • 0.30 mg vs Placebo · ANCOVA · p = 0.18 · Geomean ratio: 1.037 · 95% CI 0.982 to 1.096
SecondaryPart B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose

Change from baseline FEV1 in peak FEV1 (over 4 hours) after first dose

Time frame:
Day 1
Reported as:
Mean · L
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Peak FEV1 (Over 4 Hours) After 1st Dose0.253 ± 0.07720.311 ± 0.15320.337 ± 0.11080.079 ± 0.0914
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.162 · 95% CI 1.122 to 1.203
  • 1 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.150 · 95% CI 1.111 to 1.190
  • 0.30 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.112 · 95% CI 1.074 to 1.152
SecondaryPart B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose

Change from baseline FEV1 in average FEV1 (over 4 hours) on Day 1

Time frame:
Day 1
Reported as:
Mean · L
Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Average FEV1 (Over 4 Hours) After 1st Dose0.144 ± 0.07620.204 ± 0.11620.224 ± 0.0905-0.017 ± 0.1284
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.157 · 95% CI 1.119 to 1.196
  • 1 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.147 · 95% CI 1.110 to 1.186
  • 0.30 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.105 · 95% CI 1.068 to 1.142
SecondaryPart B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose

Change from baseline FEV1 in average FEV1 (over 12 hours) on Day 1

Time frame:
Day 1
Reported as:
Mean · L
Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose
L0.30 mg1 mg3 mgPlacebo
Part B: Change From Baseline in Average FEV1 (Over 12 Hours) After 1st Dose0.047 ± 0.09140.102 ± 0.13060.085 ± 0.0659-0.058 ± 0.1444
Statistical analysis
  • 3 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.098 · 95% CI 1.059 to 1.137
  • 1 mg vs Placebo · ANCOVA · p = <0.0001 · Geomean ratio: 1.111 · 95% CI 1.072 to 1.150
  • 0.30 mg vs Placebo · ANCOVA · p = 0.0003 · Geomean ratio: 1.070 · 5% CI 1.033 to 1.109
SecondaryPart 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

Time frame:
Day 1
Reported as:
Median · mins
Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action)
mins0.30 mg1 mg3 mg
Part B: RPL554 Plasma Pharmacokinetic Parameter (Onset of Action)37.0 (3 to 120)27.5 (5 to 120)19.0 (5 to 91)
Statistical analysis
  • 1 mg vs 3 mg · Hodges-Lehmann · p = 0.47 · Median difference (final values): 8.5
  • 0.30 mg vs 3 mg · Hodges-Lehmann · p = 0.0059 · Mean difference (final values): 18.0
SecondaryPart B: Safety and Tolerability / Hematology Safety Assessments

Number of patients with treatment-emergent hematology abnormal laboratory assessments

Time frame:
1 day

Results for this outcome have not been posted.

SecondaryPart B: Safety and Tolerability / Blood Chemistry Safety Assessments

Number of patients with treatment-emergent blood chemistry abnormal laboratory assessments

Time frame:
1 day

Results for this outcome have not been posted.

SecondaryPart B: Safety and Tolerability / Urinalysis Safety Assessments

Number of patients with treatment-emergent urinalysis abnormal laboratory assessments

Time frame:
1 day

Results for this outcome have not been posted.

SecondaryPart B: Safety and Tolerability / Supine Vital Signs - Pulse Rate

Number of patients with treatment-emergent abnormal vital signs (pulse rate in bpm)

Time frame:
Start of treatment to day 1

Results for this outcome have not been posted.

SecondaryPart B: Safety and Tolerability / Supine Vital Signs - Blood Pressure

Number of patients with treatment-emergent abnormal vital signs (blood pressure in mm Hg)

Time frame:
Start of treatment to day 1

Results for this outcome have not been posted.

SecondaryPart B: Safety and Tolerability / ECG - QTcF

Number of patients with treatment-emergent abnormal ECG parameters, QTcF in msec

Time frame:
Start of treatment to day 70

Results for this outcome have not been posted.

SecondaryPart B: Safety and Tolerability / ECG - Heart Rate

Number of patients with treatment-emergent abnormal ECG parameters, heart rate in bpm

Time frame:
Start of treatment to day 70

Results for this outcome have not been posted.

Adverse events

Collected over Part A: 24 hours. Part B: Approximately 70 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
0.10 mg/Part A0/6 (0%)0/6 (0%)2/6 (33.3%)
0.30 mg/Part A0/7 (0%)0/7 (0%)1/7 (14.3%)
1 mg/Part A0/6 (0%)0/6 (0%)1/6 (16.7%)
3 mg/Part A0/7 (0%)0/7 (0%)2/7 (28.6%)
6 mg/Part A0/7 (0%)0/7 (0%)4/7 (57.1%)
Placebo/Part A0/7 (0%)0/7 (0%)2/7 (28.6%)
Part B/0.30 mg0/24 (0%)0/24 (0%)3/24 (12.5%)
Part B/1 mg0/23 (0%)0/23 (0%)4/23 (17.4%)
Part B/3 mg0/23 (0%)0/23 (0%)2/23 (8.7%)
Part B/Placebo0/25 (0%)0/25 (0%)3/25 (12%)
Most frequent other events
Showing 10 of 21
Most frequent other events
Event0.10 mg/Part A0.30 mg/Part A1 mg/Part A3 mg/Part A6 mg/Part APlacebo/Part APart B/0.30 mgPart B/1 mgPart B/3 mgPart B/Placebo
HeadacheNervous system disorders0/60/71/61/72/71/71/241/230/230/25
SyncopeNervous system disorders1/60/70/60/70/70/70/240/230/230/25
COPDRespiratory, thoracic and mediastinal disorders1/60/70/60/70/70/70/240/230/231/25
Dry throatRespiratory, thoracic and mediastinal disorders1/60/70/60/70/70/70/240/230/230/25
NasopharyngitisInfections and infestations0/61/70/60/71/71/70/240/230/230/25
RhinitisInfections and infestations0/60/70/60/71/70/70/240/230/230/25
Upper respiratory tract infectionInfections and infestations0/60/70/60/70/71/70/240/230/230/25
ContusionInjury, poisoning and procedural complications0/60/70/60/71/70/70/240/230/230/25
Productive coughRespiratory, thoracic and mediastinal disorders0/60/70/60/70/71/70/240/230/230/25
Dermatitis contactSkin and subcutaneous tissue disorders0/60/70/61/70/70/70/240/230/230/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)0.10 mg0.30 mg1 mg3 mg6 mgPlaceboTotal
Mean66.8 ± 4.9271.4 ± 1.2764.3 ± 7.8767.1 ± 6.7263.1 ± 8.7164.4 ± 6.6066.3 ± 6.67
Sex: Female, Male
Sex: Female, Male(Participants)0.10 mg0.30 mg1 mg3 mg6 mgPlaceboTotal
Female24232316
Male43445424
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)0.10 mg0.30 mg1 mg3 mg6 mgPlaceboTotal
Hispanic or Latino0000000
Not Hispanic or Latino67677740
Unknown or Not Reported0000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)0.10 mg0.30 mg1 mg3 mg6 mgPlaceboTotal
American Indian or Alaska Native0000000
Asian0000000
Native Hawaiian or Other Pacific Islander0000000
Black or African American0000000
White67677740
More than one race0000000
Unknown or Not Reported0000000
Region of Enrollment
Region of Enrollment(participants)0.10 mg0.30 mg1 mg3 mg6 mgPlaceboTotal
United Kingdom67677740
08

Study locations

2 sites
  • Respiratory Clinical Trials Ltd
    London, W1G 8HU, United Kingdom
  • Medicines Evaluation Unit Limited
    Wythenshawe, M23 9QZ, United Kingdom
09

References and documents

Study documents

  • Study protocol · Dec 24, 2019
  • Statistical analysis plan · Jan 19, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 21, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04091360
Lead sponsor
Verona Pharma plc
Collaborators
Iqvia Pty Ltd
Responsible party
Sponsor
First posted
Sep 16, 2019
Start date
Apr 29, 2019
Primary completion
Dec 10, 2020
Completion
Jan 21, 2021
Results posted
Jul 25, 2022
Last update
Sep 21, 2022

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2022. You cannot join it, but the record below documents what was studied.

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