Study Evaluating 5 Doses of RPL554 and Placebo in COPD Patients Via a Dry Powder Inhaler

NCT04027439 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RPL554-DP-201
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (4)

• Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC0-12)

  RPL554 Plasma pharmacokinetics AUC0-12 (Area under the Curve) after single dose

  Day 1

• Part A: RPL554 Plasma Pharmacokinetic Parameter (AUC 0-t)

  RPL554 Area under the curve at maximum concentration after a single dose

  Day 1

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

  RPL554 Plasma pharmacokinetics Half-life concentration after a single dose

  Day 1

• Part B: Change From Baseline in Peak FEV1 (Over 4 Hours)

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

  Day 7

Secondary Outcomes (29)

• Part A: Change From Baseline in Average FEV1 (Over 4 Hours)

  Day 1

• Part A: Change From Baseline in Average FEV1 (Over 12 Hours)

  Day 1

• Part A: Change From Baseline in Peak FEV1 (Over 4 Hours)

  Day 1

• Part A: Safety and Tolerability / Hematology Safety Assessments

  Day 1

• Part A: Safety and Tolerability / Blood Chemistry Safety Assessments

  Day 1

Study Arms (2)

Part A: RPL554

ACTIVE COMPARATOR

Placebo controlled, parallel group single dose. Five of the 6 treatment arms will be double-blind and one will be single-blind

Drug: Part A: RPL554; Drug: Placebos

Part B: RPL554

ACTIVE COMPARATOR

Double-blind, placebo-controlled, complete block cross-over

Drug: Part B: RPL554; Drug: Placebos

Interventions

Part A: RPL554 DRUG

1 dose of either 50mcg/100mcg/1500mcg/3000mcg/6000mcg or placebo via dry powder inhaler

Part A: RPL554

Part B: RPL554 DRUG

Patients will receive 4 or 5 repeat dose treatments in crossover fashion - doses will be confirmed after Part A

Part B: RPL554

Placebos DRUG

Part A: 1 dose of either 50ncg/100ncg/1500ncg/3000ncg/6000ncg or placebo via dry powder inhaler. Part B: Patients will receive 4 or 5 repeat dose treatments in crossover fashion - doses will be confirmed after Part A.

Part A: RPL554; Part B: RPL554

Eligibility Criteria

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

You may qualify if:

• Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
• 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
• Capable of complying with all study restrictions and procedures including ability to use the DPI correctly.
• Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
• COPD diagnosis for 1 year \[prior to screening
• Ability to perform acceptable and reproducible spirometry.
• Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating the following:
• FEV1/Forced Vital Capacity (FVC) ratio of ≤0.70
• FEV1 ≥40 % and ≤80% of predicted normal
• ≥150 mL increase from pre-bronchodilator FEV1
• Clinically stable COPD in the 4 weeks prior to Screening and during the period between Screening and Part A.
• 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, within 3 months of Screening or prior to Part A.
• A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to Part A.
• 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 immunosuppressive therapy, including oral corticosteroids
• Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.
• History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.
• Received an experimental drug within 30 days or five half lives, whichever is longer.
• Patients with uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant.
• Documented cardiovascular disease, including any history of arrhythmias, angina, recent (\<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months prior to Screening
• Use of non-selective oral β-blockers.
• Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.

Sponsors & Collaborators

• Verona Pharma plc: lead
• Iqvia Pty Ltd: collaborator

Study Sites (1)

VitaLink Research -- Union

Union, South Carolina, 29379, United States

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: Verona Pharma
• Organization: Verona Pharma

info@veronapharma.com

+44 (0)203 283 4200

Study Officials

• J Boscia, MD

  Vitalink Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 9, 2019
• First Posted: July 22, 2019
• Study Start: December 10, 2018
• Primary Completion: May 23, 2019
• Study Completion: May 23, 2019
• Last Updated: September 26, 2022
• Results First Posted: May 7, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)