A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Repeat Doses of RV1729 for 28 Days in Patients With COPD

NCT02140346 | Completed Phase 1

• 2 other identifiers: STN0022014-000089-23
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

RV1729 is a new medicine being developed for the potential treatment of asthma and smoking related lung disease (also known as chronic obstructive pulmonary disease - COPD). The objective of this study is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics repeat doses of RV1729 in patients with COPD for 28 days.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (7)

• Incidence of treatment emergent adverse events

  Assessment of the number of adverse events reported by subjects following dosing

  56 days

• ECG assessment (12 lead ECG)

  Change from pre-dose values

  56 days

• Vital sign assessment (blood pressure and heart rate)

  Change from pre-dose values

  56 days

• Clinical laboratory assessments (blood and urine samples)

  Change from pre-dose values

  56 days

• Spirometry assessment (FEV1 & FVC)

  Change from pre-dose values

  56 days

• Use of rescue medication

  Assessment of the number of occasions subjects are required to administer rescue medication

  29 days

• Peak expiratory flow (PEF)

  Change from pre-dose values

  56 days

Secondary Outcomes (1)

• Plasma RV1729 levels

  Days 1, 14 & 28 - 9 samples per day; Days 7, 21, 26 and 27 - 1 sample per day; Days 31 to 56 - 5 samples

Other Outcomes (4)

• Serum biomarkers (measuring markers of inflammation in the blood)

  Days 1, 14 & 28 - 3 samples per day; Days 7 & 21 - 1 sample per day; Day 56 - 1 sample

• Exhaled breath condensate (measuring markers of oxidative stress)

  Days 1, 14 & 28 - 2 samples per day

• Sputum cell counts (measuring markers of inflammation in sputum)

  Days 14, 21 & 26 - 1 sample per day

Study Arms (2)

28 day repeat dose (low dose)

EXPERIMENTAL

Drug: RV1729 28 day repeat dose; Drug: RV1729 matching placebo 28 day repeat dose

28 day repeat dose (high dose)

EXPERIMENTAL

Drug: RV1729 28 day repeat dose; Drug: RV1729 matching placebo 28 day repeat dose

Interventions

RV1729 28 day repeat dose DRUG

Safety and tolerability of repeat doses

28 day repeat dose (high dose); 28 day repeat dose (low dose)

RV1729 matching placebo 28 day repeat dose DRUG

Safety and tolerability of repeat doses

28 day repeat dose (high dose); 28 day repeat dose (low dose)

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Be a man or a woman of non-child-bearing potential aged 40 to 75 years
• Women of non-childbearing potential must be either amenorrhoeic \>1 year with an appropriate clinical profile or permanently sterilised
• Women must agree not to donate eggs (ova, oocytes) from Screening until at least 6 months after the final dose of study medication
• Men must be willing to use one form of contraception (with documented failure rate less than 1%) and agree not to donate sperm from Screening to 90 days post last dose of study agent
• Chronic obstructive pulmonary disease diagnosis with symptoms compatible with COPD for at least 1 year before Screening.
• Severity of disease: subjects who conform to the current severity classification for Global Initiative for Chronic Obstructive Lung Disease (GOLD, 2014) Grade II/III
• On a background therapy of inhaled steroid with or without the addition of long-acting bronchodilators (either long-acting beta agonists \[LABAs\] or long-acting muscarinic antagonists \[LAMAs\]).
• Be able to produce an acceptable induced sputum sample at the Screening visit.
• Capable of complying with all study restrictions and procedures including ability to use the study inhaler correctly.
• A current or previous smoker with a smoking history of ≥10 pack years.
• Have a 12 lead ECG recording consistent with normal cardiac function at the Screening visit and pre-dose Day 1

You may not qualify if:

• A history of life-threatening COPD including respiratory arrest, intensive care unit admission and/or requiring intubation.
• A history of more than one hospitalisation for COPD in the 2 years before Screening.
• Evidence of cor pulmonale, clinically significant pulmonary hypertension or chronic use of oxygen.
• Upper or lower respiratory tract infection, including exacerbation of COPD, requiring augmentation of therapy within 6 weeks of Screening.
• Other respiratory disorders: subjects with a history of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis or other chronic pulmonary diseases.
• A chest X-ray at Screening (or within 6 months prior to the Screening visit) showing abnormalities, which in the opinion of the Investigator are clinically significant and unrelated to COPD.
• A history of chronic disease including, but not limited to, unstable or uncontrolled hypertension (or been diagnosed with hypertension in the 6 months before Screening), sleep apnoea, cardiovascular, endocrine, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological or ophthalmic diseases that the Investigator believes are clinically significant e.g., unstable and could impact subject safety by participation in the study.
• Previous lung resection or lung reduction surgery.
• Have a clinical abnormality or laboratory parameters outside the reference range at Screening or Day -1.
• Liver function test results (ALT, aspartate amino transferase and gamma glutamyl transferase) \>2 x ULN (upper limit of normal) at Screening or on Day -1.
• Chronic liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B virus (HBV) infection or hepatitis C antibodies.
• Unable or unwilling to undergo multiple venepuncture procedures or the subject has poor access to veins suitable for cannulation.
• If a woman, has a positive serum pregnancy test at Screening.
• Definite or suspected history of drug or alcohol abuse within the previous 5 years.

Sponsors & Collaborators

• Respivert Ltd: lead

Study Sites (2)

Unknown Facility

Belfast, BT9 6AD, United Kingdom

Location

Unknown Facility

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

6-(2-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)methyl)-3-(2-chlorobenzyl)-4-oxo-3,4-dihydroquinazolin-5-yl)-N,N-bis(2-methoxyethyl)hex-5-ynamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Liza O'Dowd, MD

  Sponsor GmbH

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 14, 2014
• First Posted: May 16, 2014
• Study Start: August 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 2, 2015

Record last verified: 2015-07

Locations

GB (2)