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

NCT ID: NCT04027439

Last Updated: 2022-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-10
• Study Completion Date: 2019-05-23

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).

Detailed Description

The study will consist of two parts. Part A is a parallel group, placebo-controlled single dose study to ascertain the Pharmacokinetics (PK) profile, safety and bronchodilator effect of RPL554 administered via dry powder inhaler (DPI). Five of the 6 treatment arms will be double-blind and one will be single-blind (due to the different number of capsules administered). Part B is a placebo-controlled, complete block cross-over, repeat dose study to assess the bronchodilator effect of repeat doses of RPL554 delivered via a DPI.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A: RPL554

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

Group Type: ACTIVE_COMPARATOR

Part A: RPL554

Intervention Type: DRUG

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

Placebos

Intervention Type: 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 B: RPL554

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

Group Type: ACTIVE_COMPARATOR

Part B: RPL554

Intervention Type: DRUG

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

Placebos

Intervention Type: 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.

Interventions

Part A: RPL554

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

Intervention Type: DRUG

Part B: RPL554

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

Intervention Type: DRUG

Placebos

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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

3. 12-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

4. Capable of complying with all study restrictions and procedures including ability to use the DPI correctly.

5. Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.

6. COPD diagnosis for 1 year [prior to screening

7. Ability to perform acceptable and reproducible spirometry.

8. 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

9. Clinically stable COPD in the 4 weeks prior to Screening and during the period between Screening and Part A.

10. A chest X-ray showing no abnormalities, which are both clinically significant and unrelated to COPD.

11. Meet the concomitant medication restrictions and be expected to do so for the rest of the study.

12. 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.

Exclusion Criteria

1. A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.

2. COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, within 3 months of Screening or prior to Part A.

3. A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to Part A.

4. Intolerance or hypersensitivity to tiotropium, olodaterol, atropine, ipratropium, or RPL554.

5. Evidence of cor pulmonale or clinically significant pulmonary hypertension.

6. Other respiratory disorders

7. Previous lung resection or lung reduction surgery.

8. Use of immunosuppressive therapy, including oral corticosteroids

9. Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.

10. History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.

11. Received an experimental drug within 30 days or five half lives, whichever is longer.

12. 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.

13. 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

14. Use of non-selective oral β-blockers.

15. 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.

16. A disclosed history or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.

17. Required use of oxygen therapy, even on an occasional basis.

18. History of malignancy of any organ system within 5 years, with the exception of localized skin cancers (basal or squamous cell).

19. Clinically significant abnormal values for safety laboratory tests (hematology, biochemistry, viral serology or urinalysis) at Screening, as determined by the Investigator. In particular, alanine aminotransferase or aspartate aminotransferase cannot be more than twice the upper limit of normal.

20. Any other reason that the Investigator considers makes the patient unsuitable to participate.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iqvia Pty Ltd

INDUSTRY

Sponsor Role: collaborator

Verona Pharma plc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J Boscia, MD

Role: PRINCIPAL_INVESTIGATOR

Vitalink Research

Locations

VitaLink Research -- Union

Union, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RPL554-DP-201

Identifier Type: -

Identifier Source: org_study_id