Trial Outcomes & Findings for A Study of RPL554 in Patients With Cystic Fibrosis (NCT NCT02919995)

Results Overview

Area under the curve (AUC)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment

Results posted on

2024-05-21

Participant Flow

16 patients were screened; six patients failed screening. Patients had to discontinue long acting bronchodilators on the day prior to screening and short acting bronchodilators for 8 hours before all spirometry assessments

Participant milestones

Participant milestones
Measure	Higher Dose RPL554/Lower Dose RPL554/Placebo Single dose of inhaled 6 mg RPL554 in Period 1, Single inhaled dose of 1.5 mg RPL554 in Period 2, placebo in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Lower Dose RPL554/Placebo/Higher Dose RPL554 Single dose of inhaled 1.5 mg RPL554 in Period 1, single inhaled dose of placebo in Period 2, single inhaled dose of 6 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Higher Dose RPL554/Plaebo/Lower Dose RPL554 Single inhaled dose of 6 mg RPL554 in Period 1, single inhaled dose of placebo in Period 2, single inhaled dose of 1.5 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Lower Dose RPL554/Higher Dose RPL554/Placebo Single inhaled dose of 1.5 mg RPL554 in Period 1, single inhaled dose of 6 mg RPL554 in Period 2, single inhaled dose of placebo in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Placebo/Higher Dose RPL554/Lower Dose RPL554 Single inhaled dose of placebo in Period 1, single inhaled dose of 6 mg RPL554 in Period 2, single inhaled dose of 1.5 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Placebo/Lower Dose RPL554/Higher Dose RPL554 Single inhaled dose of placebo in Period 1, single inhaled dose of 1.5 mg RPL554 in Period 2, single inhaled dose of 6 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser
Overall Study STARTED	1	2	2	2	1	2
Overall Study COMPLETED	1	2	2	2	1	1
Overall Study NOT COMPLETED	0	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Higher Dose RPL554/Lower Dose RPL554/Placebo Single dose of inhaled 6 mg RPL554 in Period 1, Single inhaled dose of 1.5 mg RPL554 in Period 2, placebo in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Lower Dose RPL554/Placebo/Higher Dose RPL554 Single dose of inhaled 1.5 mg RPL554 in Period 1, single inhaled dose of placebo in Period 2, single inhaled dose of 6 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Higher Dose RPL554/Plaebo/Lower Dose RPL554 Single inhaled dose of 6 mg RPL554 in Period 1, single inhaled dose of placebo in Period 2, single inhaled dose of 1.5 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Lower Dose RPL554/Higher Dose RPL554/Placebo Single inhaled dose of 1.5 mg RPL554 in Period 1, single inhaled dose of 6 mg RPL554 in Period 2, single inhaled dose of placebo in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Placebo/Higher Dose RPL554/Lower Dose RPL554 Single inhaled dose of placebo in Period 1, single inhaled dose of 6 mg RPL554 in Period 2, single inhaled dose of 1.5 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Placebo/Lower Dose RPL554/Higher Dose RPL554 Single inhaled dose of placebo in Period 1, single inhaled dose of 1.5 mg RPL554 in Period 2, single inhaled dose of 6 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser
Overall Study Adverse Event	0	0	0	0	0	1

Baseline Characteristics

A Study of RPL554 in Patients With Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Higher Dose RPL554/Lower Dose RPL554/Placebo n=1 Participants Single dose of inhaled 6 mg RPL554 in Period 1, single dose of inhaled 1.5 mg RPL554 in Period 2, single inhaled dose of placebo in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Lower Dose RPL554/Placebo/Higher Dose RPL554 n=2 Participants Single dose of inhaled 1.5 mg RPL554 in Period 1, single dose of inhaled placebo RPL554 in Period 2, single dose of 6 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Higher Dose RPL554/Placebo/Lower Dose RPL554 n=2 Participants Single dose of inhaled 6 mg RPL554 in Period 1, single dose of inhaled placebo in Period 2, single dose of inhaled 1.5 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Lower Dose RPL554/Higher Dose RPL554/Placebo n=2 Participants Single dose of inhaled 1.5 mg RPL554 in Period 1, single dose of inhaled 6 mg RPL554 in Period 2, single inhaled dose of placebo in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Placebo/Higher Dose RPL554/Lower Dose RPL554 n=1 Participants Single dose of inhaled placebo in Period 1, single dose of inhaled 6 mg RPL554 in Period 2, single dose of inhaled 1.5 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Placebo/Lower Dose RPL554/Higher Dose RPL554 n=2 Participants Single dose of inhaled placebo in Period 1, single dose of inhaled 1.5 mg RPL554 in Period 2, single dose of inhaled 6 mg RPL554 in Period 3 RPL554: RPL554 suspension administered using a nebuliser Placebo: Placebo solution administered using a nebuliser	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	10 Participants n=8 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	4 Participants n=8 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	6 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	10 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment

Population: All randomised patients with blood sampling performed after at least one dose of RPL554 and with data sufficient to calculate pharmacokinetic parameters.

Area under the curve (AUC)

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=9 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
AUC by Dose	7699 pg*h/mL Standard Deviation 2965.7	2342 pg*h/mL Standard Deviation 1029.9	—

PRIMARY outcome

Timeframe: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose

Population: All randomised patients with blood sampling performed after at least one dose of RPL554 and with data sufficient to calculate pharmacokinetic parameters.

Maximum plasma concentration (Cmax) after a single dose of RPL554

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=9 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
Maximum Plasma Concentration After Each Dose	828.3 pg/mL Standard Deviation 256.1	270.1 pg/mL Standard Deviation 91.9	—

PRIMARY outcome

Timeframe: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose

Population: All randomised patients with blood sampling performed after at least one dose of RPL554 and with data sufficient to calculate pharmacokinetic parameters.

Time to maximum concentration (Tmax) after a single dose of RPL554

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=9 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
Time to Maximum Plasma Concentration After Each Dose	1.53 hours Standard Deviation 0.66	1.33 hours Standard Deviation 0.62	—

PRIMARY outcome

Timeframe: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose

Population: All randomised patients with blood sampling performed after at least one dose of RPL554 and with data sufficient to calculate pharmacokinetic parameters.

Half life (t1/2) of RPL554

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=9 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
Half Life for Each Dose	10.14 Hours Standard Deviation 3.1	7.52 Hours Standard Deviation 3.3	—

SECONDARY outcome

Timeframe: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose after treatment

Population: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamic parameters on at least two study visits.

Maximum Forced expired volume in one second (FEV1) measured using spirometry

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=10 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo n=10 Participants Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
Peak FEV1 for Each Treatment	2.384 Liters Standard Deviation 0.73	2.247 Liters Standard Deviation 0.72	2.256 Liters Standard Deviation 0.71

SECONDARY outcome

Timeframe: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose

Population: All randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamic parameters on at least two study visits.

Area under the curve for FEV1 over 4 hours measured using spirometry

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=10 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo n=10 Participants Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
AUC FEV1(0-4h)	2.313 Liters Standard Deviation 0.73	2.194 Liters Standard Deviation 0.72	2.133 Liters Standard Deviation 0.73

SECONDARY outcome

Timeframe: Pre dose and 15 and 30 minutes and 1, 2, 4 and 6 hours post dose

Population: all randomized patients with sufficient data collected after intake of study treatment to compute the pharmacodynamic parameters on at least two study visits.

Area under the curve FEV1 over 6 hours measured using spirometry

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=10 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo n=10 Participants Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
AUC FEV1(0-6h)	2.304 Liters Standard Deviation 0.74	2.188 Liters Standard Deviation 0.73	2.133 Liters Standard Deviation 0.73

SECONDARY outcome

Timeframe: pre dose and 15 and 30 minutes and 1, 2, 4, 6 and 8 hours post dose

Population: All randomised patients with sufficient data collected after intake of study treatment to compute the pharmacodynamic parameters on at least two study visits.

Area under the curve for FEV1 over 8 hours measured using spirometry

Outcome measures

Outcome measures
Measure	Higher Dose RPL554 n=9 Participants Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=10 Participants Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo n=10 Participants Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
AUC FEV1(0-8h)	2.287 Liters Standard Deviation 0.75	2.185 Liters Standard Deviation 0.74	2.130 Liters Standard Deviation 0.74

Adverse Events

Higher Dose RPL554

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Lower Dose RPL554

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Higher Dose RPL554 n=9 participants at risk Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=10 participants at risk Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo n=10 participants at risk Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
Infections and infestations exacerbation of cystic fibrosis	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days

Other adverse events

Additional Information

Brian Maurer

Verona Pharma plc

Phone: +19147675037

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator shall not be permitted to present at symposia, national or regional professional meetings, nor publish in journals, theses or dissertations, or otherwise of their own choosing, methods and results of the Clinical Trial without the prior written approval of the Sponsor. Any such approved presentation or publication shall acknowledge the Sponsor as the sponsor of the Clinical Trial and owner of the results of the Clinical Trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Higher Dose RPL554 n=9 participants at risk Single dose of inhaled 6 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Lower Dose RPL554 n=10 participants at risk Single dose of inhaled 1.5 mg RPL554 RPL554: RPL554 suspension administered using a nebuliser	Placebo n=10 participants at risk Inhaled placebo dose Placebo: Placebo solution administered using a nebuliser
Investigations Forced expiratory volume decreased	11.1% 1/9 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Investigations Pulmonary function test decreased	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days
Cardiac disorders Tachycardia	22.2% 2/9 • Number of events 2 • From informed consent through study completion, up to 52 days	20.0% 2/10 • Number of events 2 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days
Immune system disorders Drug hypersensitivity	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Respiratory, thoracic and mediastinal disorders Cough	22.2% 2/9 • Number of events 2 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 2 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/9 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	11.1% 1/9 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Nervous system disorders Headache	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Nervous system disorders Syncope	0.00% 0/9 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days
General disorders Chest discomfort	11.1% 1/9 • Number of events 1 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Gastrointestinal disorders Abdominal pain lower	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Gastrointestinal disorders Dry mouth	0.00% 0/9 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Infections and infestations Infective exacerbation of cystic fibrosis	0.00% 0/9 • From informed consent through study completion, up to 52 days	10.0% 1/10 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days
Infections and infestations Oral candidiasis	11.1% 1/9 • Number of events 1 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days	0.00% 0/10 • From informed consent through study completion, up to 52 days