SAD/MAD Study of a New Formulation of Nebulised RPL554 in Healthy Subjects and COPD Subjects

NCT02307162 | Completed Phase 1 DMC

• 1 other identifier: RPL554-007-2014
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the safety of single doses and multiple doses of a new formulation of RPL554 in healthy subjects and subjects with chronic obstructive pulmonary disorder.

Conditions

Inflammatory Disorder of the Respiratory Tract; Chronic Obstructive Pulmonary Disorder

Keywords

COPD

Outcome Measures

Primary Outcomes (6)

• Adverse events

  Adverse events

  From screening until last visit (up to 10 days after last dose)

• Vital signs

  Blood pressure and pulse rate

  Pre-dose, up to 24 hours post last dose and last visit

• Laboratory safety assessments

  Biochemistry, haematology and urinalysis

  Pre-dose, up to 24 hours post last dose and last visit

• ECG

  ECG

  Pre-dose, up to 24 hours post last dose and last visit

• Physical Examination

  Pre-dose, 24 hours post last dose and last visit

• Holter Monitoring

  Continuous heart monitoring

  24 hours post dose

Secondary Outcomes (1)

• Pharmacokinetics (trough measurement Blood sampling for RPL554 concentration)

  24 hour profile after first and last dose, trough measurement on Days 2-5 for Parts B and C

Study Arms (2)

Dummy solution

PLACEBO COMPARATOR

Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C)

Drug: Placebo

RPL554 suspension

EXPERIMENTAL

Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C). Starting dose in Part A to be 1.5mg/mL with planned up to 2 fold increments. Doses in Part B will be selected from Part A. Doses in Part C to be selected from Part B

Drug: RPL554

Interventions

RPL554 DRUG

Phosphodiesterase 3 and 4 Inhibitor

RPL554 suspension

Placebo DRUG

Dummy solution

Dummy solution

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Males following contraception requirements, and agree not to donate sperm during study
• lead ECG within normal range and no clinically significant abnormality
• Screening Holter report (minimum 18 hours) recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of subject safety or which may significantly impair interpretation
• Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
• Body weight ≥50 kg.
• Negative for HIV, HBV and HCV
• Negative cotinine tests prior to randomisation.
• Males aged 18 and 50 years
• Considered to be healthy
• Vital sign assessments within ranges:
• Systolic blood pressure 90 to 140 mmHg
• Diastolic blood pressure 50 to 90 mmHg
• Heart rate 45 to 90 bpm
• BMI 18 and 33 kg/m2 .

You may not qualify if:

• Respiratory tract infection (both upper and lower) treated with antibiotics in last 12 weeks
• Clinically significant abnormal values for safety laboratory tests or physical examination
• History or suspected history of drug or alcohol abuse within the past 5 years.
• Known allergy to the study drug or any of the excipients of the formulation.
• Donated blood or blood products or had substantial loss of blood (more than 500 mL) in last 4 weeks or intention to donate blood or blood products during the study.
• Received an experimental drug or used an experimental medical device within 3 months or within a period less than 5 times the drug's half-life, whichever is longer
• Pre-planned surgery or procedures that would interfere with the conduct of the study.
• Employee of the Investigator or study site or family members of the employees or the Investigator.
• History of regular alcohol consumption within last 6 months
• Unable or unwilling to comply fully with the study protocol.
• Mentally or legally incapacitated.
• Unable or unwilling to undergo multiple venepuncture procedures or having poor access to veins suitable for cannulation.
• History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin.
• Any other reason that the Investigator considers makes the subject unsuitable to participate.
• Positive test for alcohol or drugs of abuse

Sponsors & Collaborators

• Verona Pharma plc: lead

Study Sites (1)

Medicines Evaluation Unit

Manchester, M23 9QP, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

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

Study Officials

• Dave Singh

  Medicines Evaluation Unit, Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2014
• First Posted: December 4, 2014
• Study Start: December 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: October 28, 2015

Record last verified: 2015-10

Locations

GB (1)