Bronchodilator Effect of RPL554 Administered in Addition to Tiotropium/Olodaterol in Patients With COPD

NCT03673670 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RPL554-CO-204
• Study Type: interventional
• Target: 79
• Locations: 2 countries
• Sites: 4

Brief Summary

The study investigates the effect of 3 days of twice daily treatment of two different doses of RPL554 (a phosphodiesterase \[PDE\]3/4 inhibitor) or placebo, each administered in addition to once daily tiotropium/olodaterol (Respimat) in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Patients will receive each of the three treatment combinations in a randomized sequence using a crossover design

Conditions

COPD

Keywords

COPD; Bronchodilation; FEV1

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Peak FEV1 on Day 3

  Change from baseline FEV1 to peak FEV1 (measured as the greatest value in the 4 hours post-dose after the morning dose) on Day 3

  Change from pre-dose at 5, 15 and 30 minutes and 1, 1.5, 2 & 4 hours on Day 3

Secondary Outcomes (13)

• Change From Baseline to Trough FEV1 on Day 4

  Change from pre-dose on Day 1 to pre-dose on Day 4

• Change From Baseline in AUC0-4h FEV1 on Day 3

  Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4 hours on Day 3 (after the morning dose)

• Change From Baseline in AUC0-12h FEV1 on Day 3

  Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4, 6, 8, 12 hours on Day 3 (after the morning dose)

• Change From Baseline in Peak FEV1 on Day 1

  Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4 hours on Day 1 (after the morning dose), with the maximum change reported

• Change From Baseline in Peak FEV1 After Evening Dose on Day 3

  Change from pre-dose to each of the ollowing timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4 hours on Day 3 (after the evening dose), with the maximum change reported

Study Arms (3)

1.5 mg RPL554 and tiotropium/olodaterol

EXPERIMENTAL

1.5 mg RPL554 suspension administered using a nebulizer twice daily plus 5 mcg/5 mcg tiotropium/olodaterol (Respimat) administered once daily

Drug: RPL554 Suspension; Drug: Tiotropium/olodaterol (Respimat)

6 mg RPL554 and tiotropium/olodaterol

EXPERIMENTAL

6 mg RPL554 suspension administered using a nebulizer twice daily plus 5 mcg/5 mcg tiotropium/olodaterol (Respimat) administered once daily

Drug: RPL554 Suspension; Drug: Tiotropium/olodaterol (Respimat)

Placebo and tiotropium/olodaterol

EXPERIMENTAL

Placebo administered using a nebulizer twice daily plus 5 mcg/5 mcg tiotropium/olodaterol (Respimat) administered once daily

Drug: Placebo; Drug: Tiotropium/olodaterol (Respimat)

Interventions

RPL554 Suspension DRUG

A PDE3/4 inhibitor

1.5 mg RPL554 and tiotropium/olodaterol; 6 mg RPL554 and tiotropium/olodaterol

Placebo DRUG

A placebo solution

Placebo and tiotropium/olodaterol

Tiotropium/olodaterol (Respimat) DRUG

An anticholinergic/β-agonist combination medication

1.5 mg RPL554 and tiotropium/olodaterol; 6 mg RPL554 and tiotropium/olodaterol; Placebo and tiotropium/olodaterol

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Male or female aged 40 and 80 years
• 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
• 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
• Screening Holter report with a minimum of 18 hours recording that is able to be evaluated for rhythm analysis showing no abnormality which indicates a significant impairment of patient safety or which may significantly impair interpretation
• Capable of complying with all study restrictions and procedures including ability to use the study nebulizer and Respimat® correctly.
• Body mass index (BMI) between 18 and 36 kg/m2 and minimum weight of 45 kg.
• COPD diagnosis for at least 1 year and clinically stable COPD for 4 week
• Post-bronchodilator (two puffs of salbutamol/albuterol followed by two puffs of ipratropium) spirometry at Screening:
• Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70
• Post-bronchodilator FEV1 ≥30 % and ≤70% of predicted normal
• Demonstrates ≥150 mL increase from pre-bronchodilator FEV1
• 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.

You may not qualify if:

• A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
• COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, in the last 3 months
• A history of one or more hospitalizations for COPD in the last 12 months
• Intolerance or hypersensitivity to tiotropium, olodaterol, atropine, ipratropium, or RPL554.
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Other respiratory disorders
• Previous lung resection or lung reduction surgery.
• Use of oral COPD medications, except mucolytics, in the last 3 months
• Pulmonary rehabilitation, unless such treatment has been stable in the last 4 weeks
• History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.
• Inability to perform acceptable spirometry or whole body plethysmography
• Received an experimental drug within 30 days or five half lives, whichever is longer.
• Patients with uncontrolled disease that the Investigator believes are clinically significant. This includes any hepatic disease, or an alanine aminotransferase or aspartate aminotransferase\>2 x upper limit of normal (ULN).
• Documented cardiovascular disease: arrhythmias, angina, recent (\<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension in the last 3 months
• Use of non-selective oral β-blockers.

Sponsors & Collaborators

• Verona Pharma plc: lead

Study Sites (4)

Clinical Site Partners, LLC

Winter Park, Florida, 32789, United States

Location

Allied Biomedical Research Holdings, d/b/a Vitalink Research

Greenville, South Carolina, 29615, United States

Location

Respiratory Clinical Trials LTD,

London, W1G8HU, United Kingdom

Location

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide; olodaterol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Brian Maurer
• Organization: Verona Pharma plc

brian.maurer@veronapharma.com

+19147675037

Study Officials

• Dave Singh

  Medicines Evaluation Unit

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The nebulizer cup will be obscured so the contents are not visible to the subject and the blinded study staff.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 17, 2018
• Study Start: July 16, 2018
• Primary Completion: November 13, 2018
• Study Completion: November 13, 2018
• Last Updated: October 10, 2019
• Results First Posted: October 10, 2019

Record last verified: 2019-09

Locations

GB (2); US (2)