Dose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients

NCT03443414 | Completed Phase 2 Results

• 1 other identifier: RPL554-CO-203
• Study Type: interventional
• Target: 405
• Locations: 6 countries
• Sites: 49

Brief Summary

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.

Conditions

COPD

Keywords

COPD, bronchodilation, FEV1

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (5)

• Mean Change From Baseline FEV1 to Morning Trough FEV1 at Week 4

  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

  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

  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

  Baseline (pre-dose, Visit 2) and Week 4 (Visit 6).

• Number of Patients With Treatment Emergent Adverse Events (TEAEs)

  Up to end of study (approximately 6 weeks)

Study Arms (5)

0.75 mg RPL554

EXPERIMENTAL

Drug: RPL554 suspension

1.5 mg RPL554

EXPERIMENTAL

Drug: RPL554 suspension

3 mg RPL554

EXPERIMENTAL

Drug: RPL554 suspension

6 mg RPL554

EXPERIMENTAL

Drug: RPL554 suspension

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

RPL554 suspension DRUG

A dual PDE3/PDE 4 inhibitor

0.75 mg RPL554; 1.5 mg RPL554; 3 mg RPL554; 6 mg RPL554

Placebo DRUG

Placebo solution

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide informed consent
• Male or female aged 40 to 75 years
• Meeting specified contraception requirements
• lead electrocardiogram with heart rate 50-90 beats per minute, QT interval corrected using Fridericia's formula (QTcF) ≤450 msec (males) or ≤470 msec (females), QRS interval ≤120 msec, PR interval ≤200 msec and no clinically significant abnormalities
• Capable of complying with all study restrictions and procedures, including ability to use the study nebulizer correctly.
• Body mass index (BMI) 18 to 35 kg/m2 and minimum weight 45 kg.
• COPD diagnosis with symptoms compatible with COPD for at least 1 year
• Clinically stable COPD in the previous 4 weeks
• Ability to perform acceptable and reproducible spirometry.
• Post-bronchodilator spirometry at screening must demonstrate FEV1/forced vital capacity (FVC) ratio of ≤0.70 and FEV1 must be ≥40 % to ≤80% of predicted normal
• Chest X-ray (posterior-anterior) at screening, or chest X-ray, magnetic resonance imaging (MRI) or computed tomography (CT) scan in the last 12 months, 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 a smoking history of ≥10 pack years.
• Capable of withdrawing long acting bronchodilators until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study medication.

You may not qualify if:

• A history of life-threatening COPD including Intensive Care Unit admission and requiring intubation.
• COPD exacerbation requiring oral steroids in the previous 3 months
• A history of one or more hospitalizations for COPD in the previous 6 months
• Lower respiratory tract infection treated with antibiotics in the previous 3 months
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
• Previous lung resection or lung reduction surgery.
• Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) in the previous 3 months and throughout the study.
• Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Visit 1) and remains stable during the trial.
• A history of, or reason to believe a subject has, drug or alcohol abuse in the previous 3 years.
• Received an experimental drug within 30 days or five half-lives of the first dose
• Prior exposure to RPL554.
• Women who are pregnant or breast-feeding.
• Patients with a history of current uncontrolled disease that the Investigator believes are clinically significant.
• myocardial infarction in the previous 6 month; congestive heart failure, a history of unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.

Sponsors & Collaborators

• Verona Pharma plc: lead

Study Sites (49)

Clinic for pneumonology

Pleven, Bulgaria

Location

SHATPPD-Ruse EOOD

Rousse, Bulgaria

Location

Fifth MHAT - Sofia EAD

Sofia, Bulgaria

Location

MHAT 'Lyulin', EAD

Sofia, Bulgaria

Location

NMTH Tsar Boris III

Sofia, Bulgaria

Location

UMHAT 'Alexandrovska' EAD

Sofia, Bulgaria

Location

UMHAT 'Sveta Anna' AD

Sofia, Bulgaria

Location

Medical Center Nov

Stara Zagora, Bulgaria

Location

MediTrial s.r.o.

Jindřichův Hradec, Czechia

Location

Plicni stredisko Teplice

Teplice, Czechia

Location

Aerzte fuer Lungen- und

Berlin, Germany

Location

Charite Campus Mitte

Berlin, Germany

Location

emovis GmbH

Berlin, Germany

Location

Studienpraxis Berlin

Berlin, Germany

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt, Germany

Location

Praxis Dr. Keller

Frankfurt, Germany

Location

Inamed GmbH

Gauting, Germany

Location

PRI Pulmonary Research

Großhansdorf, Germany

Location

Hamburger Institut fuer

Hamburg, Germany

Location

Gemeinschaftspraxis Dres

Koblenz, Germany

Location

POIS Leipzig GbR

Leipzig, Germany

Location

SALVUS UG Centre for Clinial Trials

Leipzig, Germany

Location

KLB Gesundheitsforschung

Lübeck, Germany

Location

Pneumologie Odeonsplatz

Munich, Germany

Location

Pneumologische Praxis Pasing

München, Germany

Location

Ballenberger Freytag Wenisch

Neu-Isenburg, Germany

Location

Dr. Christian Schlenska

Peine, Germany

Location

CERMED

Bialystok, Poland

Location

Indywidualna Specjalistyczna

Bialystok, Poland

Location

KLIMED Marek Klimkiewicz

Bychawa, Poland

Location

Silmedic sp. z o.o.

Katowice, Poland

Location

Grazyna Pulka Specjalistyczny

Krakow, Poland

Location

Malopolskie Centrum Alergologii

Krakow, Poland

Location

Centrum Terapii Wspólczesnej

Lodz, Poland

Location

Uniwersytecki Szpital Klin

Lodz, Poland

Location

NZOZ Alergo-MEDSpecjalistyczna

Poznan, Poland

Location

ETG Network Sp z o o

Skierniewice, Poland

Location

Centrum Medyczne Pratia

Warsaw, Poland

Location

Mazowieckie Centrum Medyczne

Warsaw, Poland

Location

Centrum Badan Klinicznych

Wroclaw, Poland

Location

Specjalistyczna Opieka

Wroclaw, Poland

Location

S.C Angisan S.R.L

Bragadiru, Romania

Location

S.C Clinica Pneumomedica S.R.L

Brasov, Romania

Location

Fundatia Dr. Victor Babes

Bucharest, Romania

Location

Spitalul Clinic de Urgenta

Bucharest, Romania

Location

Spitalul Cl. Pneumoftiziologie

Cluj-Napoca, Romania

Location

Spitalul CldePneumoftiziologie

Constanța, Romania

Location

Spitalul CldePneumoftiziologie

Iași, Romania

Location

Medicines Evaluation Unit

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Brian Maurer, Senior Clinical Operations Director
• Organization: Verona Pharma

brian.maurer@veronapharma.com

(914) 767-5037

Study Officials

• Dr Singh

  Medicines Evaluation Unit (MEU)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: February 23, 2018
• Study Start: June 1, 2017
• Primary Completion: January 23, 2018
• Study Completion: February 7, 2018
• Last Updated: June 4, 2019
• Results First Posted: June 4, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (17); RO (7); BU (8); PL (14); GB (1); CZ (2)