The Effects of RPL554 on Top of Standard COPD Reliever Medications

NCT02542254 | Completed Phase 2

• 2 other identifiers: RPL554-009-20152015-002536-41
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the addition of RPL554 to standard reliever medications for chronic obstructive pulmonary disorder (COPD). All patients will receive the same six treatments in a randomised sequence:

1. 1.salbutamol,
2. 2.ipratropium,
3. 3.salbutamol + RPL554,
4. 4.ipratropium + RPL554,
5. 5.RPL554
6. 6.Placebo

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• 8 hour spirometry

  Forced expired volume in one second (FEV1) over 8 hours post-dose

  8 hours

Secondary Outcomes (9)

• 12 hour spirometry

  12 hours

• Whole body plethysmography

  4 hours

• Area under the curve (AUC)

  12 hours

• Maximum plasma concentration (Cmax)

  12 hours

• Time to maximum plasma concentration (Tmax)

  12 hours

Study Arms (6)

Salbutamol alone

ACTIVE COMPARATOR

200 micrograms salbutamol, ipratropium matched placebo and RPL554 matched placebo

Drug: Salbutamol; Drug: Ipratropium matched placebo; Drug: RPL554 matched placebo

Salbutamol and RPL554

EXPERIMENTAL

200 micrograms salbutamol, ipratropium matched placebo and 6 mg RPL554

Drug: Salbutamol; Drug: RPL554; Drug: Ipratropium matched placebo

Ipratropium

ACTIVE COMPARATOR

Salbutamol matched placebo, 40 micrograms ipratropium and RPL554 matched placebo

Drug: Ipratropium; Drug: Salbutamol matched placebo; Drug: RPL554 matched placebo

Ipratropium and RPL554

EXPERIMENTAL

Salbutamol matched placebo, 40 micrograms ipratropium and 6 mg RPL554

Drug: Ipratropium; Drug: RPL554; Drug: Salbutamol matched placebo

RPL554

EXPERIMENTAL

Salbutamol matched placebo, ipratropium matched placebo and 6 mg RPL554

Drug: RPL554; Drug: Salbutamol matched placebo; Drug: Ipratropium matched placebo

Placebo

PLACEBO COMPARATOR

Salbutamol matched placebo, ipratropium matched placebo and RPL554 matched placebo

Drug: Salbutamol matched placebo; Drug: Ipratropium matched placebo; Drug: RPL554 matched placebo

Interventions

Salbutamol DRUG

200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)

Salbutamol alone; Salbutamol and RPL554

Ipratropium DRUG

40 micrograms ipratropium administered using a pMDI

Ipratropium; Ipratropium and RPL554

RPL554 DRUG

6 mg RPL554 administered using a nebuliser

Ipratropium and RPL554; RPL554; Salbutamol and RPL554

Salbutamol matched placebo DRUG

Placebo pMDI

Ipratropium; Ipratropium and RPL554; Placebo; RPL554

Ipratropium matched placebo DRUG

Placebo pMDI

Placebo; RPL554; Salbutamol alone; Salbutamol and RPL554

RPL554 matched placebo DRUG

Nebulised placebo

Ipratropium; Placebo; Salbutamol alone

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide informed consent
• Males not donating sperm and using adequate contraception or females who are surgically sterile or postmenopausal
• lead ECG showing:Heart rate 45 to 90 bpm, QTcF≤450 msec, QRS ≤120 msec, PR interval ≤220 msec, no clinically significant abnormality
• Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
• BMI 18 to 33 kg/m2 with a minimum weight of 45 kg.
• COPD diagnosis for at least 1 year and clinically stable COPD in previous 4 weeks
• Demonstrates reversibility to bronchodilator (two puffs of salbutamol followed by two puffs of ipratropium) via spirometry:
• Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70
• Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
• ≥150 mL increase from pre-bronchodilator FEV1
• Chest X-ray showing no abnormalities
• Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
• Smoking history of ≥10 pack years.
• Capable of withdrawing from long acting bronchodilators throughout the study and short acting bronchodilators for 8 hours prior to study treatment.

You may not qualify if:

• History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
• COPD exacerbation requiring oral steroids in the previous 3 months
• History of one or more hospitalisations for COPD in the previous 12 months
• Respiratory tract infection (both upper and lower) treated with antibiotics in previous 12 weeks
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Other respiratory disorders
• Previous lung resection or lung reduction surgery.
• Oral therapies for COPD in the previous 3 months and throughout the study.
• Drug or alcohol abuse in the past 3 years
• Received an experimental drug within 3 months or five half lives, whichever is longer.
• Prior exposure to RPL554
• Patients with a history of chronic uncontrolled disease that the Investigator believes are clinically significant.
• Documented cardiovascular disease in last 3 months
• Major surgery, (requiring general anaesthesia) in the previous 6 weeks, or will not have fully recovered from surgery, or planned surgery through the end of the study.
• History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell)

Sponsors & Collaborators

• Verona Pharma plc: lead

Study Sites (1)

Medicines Evaluation Unit

Manchester, United Kingdom

Location

Related Publications (1)

• Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018 Nov 1;52(5):1801074. doi: 10.1183/13993003.01074-2018. Print 2018 Nov.

  PMID: 30166326 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Albuterol; Ipratropium; ensifentrine

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)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Dave Singh

  Medicines Evaluation Unit

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 30, 2015
• First Posted: September 4, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 9, 2016

Record last verified: 2016-09

Locations

GB (1)