Advertisement

Topics

A Randomised, Placebo-Controlled, Dose-Finding Study Of AZD9668, An Oral Inhibitor of Neutrophil Elastase, in Patients with Chronic Obstructive Pulmonary Disease Treated with Tiotropium.

06:00 EDT 31st March 2012 | BioPortfolio

Summary of "A Randomised, Placebo-Controlled, Dose-Finding Study Of AZD9668, An Oral Inhibitor of Neutrophil Elastase, in Patients with Chronic Obstructive Pulmonary Disease Treated with Tiotropium."

Abstract AZD9668 is a fully reversible, selective, oral inhibitor of neutrophil elastase, a protease implicated in chronic obstructive pulmonary disease (COPD). Efficacy, safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb trial (NCT00949975: approved by an Investigational Review Board), in patients with symptomatic COPD receiving maintenance tiotropium. The primary endpoint was pre-bronchodilator forced expiratory volume in 1 second (FEV1). Secondary endpoints included forced vital capacity and inspiratory capacity, peak expiratory flow, Breathlessness, Cough and Sputum Scale score, exercise capacity, quality of life (QoL), exacerbation assessments, safety and pharmacokinetics. Exploratory endpoints included inflammatory and tissue degradation biomarkers. A total of 838 patients were randomised to AZD9668 5 mg bid (212 patients), 20 mg bid (206 patients), 60 mg bid (202 patients) or placebo (218 patients). AZD9668 showed no effect on lung function, respiratory signs and symptoms, QoL or biomarkers. At end of treatment, the change in mean pre-bronchodilator FEV1 for AZD9668 60 mg bid compared with placebo was 0.00L (95% confidence interval: -0.05, 0.04; p = 0.873). Overall, AZD9668 was well tolerated; the numbers of patients with adverse events (AEs), serious AEs and AEs leading to discontinuation were similar in each of the four study groups. AZD9668 60 mg bid showed no clinical benefit and no effect on biomarkers of inflammation or tissue degradation when added to tiotropium in patients with COPD. These results raise important questions for future investigation of anti-inflammatory and disease-modifying agents in patients with COPD.

Affiliation

1Universitätsklinikum Giessen und Marburg, Marburg, Germany.

Journal Details

This article was published in the following journal.

Name: COPD
ISSN: 1541-2563
Pages: 111-20

Links

DeepDyve research library

PubMed Articles [32727 Associated PubMed Articles listed on BioPortfolio]

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study as...

A randomised, placebo-controlled study of the CXCR2 antagonist AZD5069 in bronchiectasis.

This randomised double-blind placebo-controlled parallel-group multicentre phase IIa study evaluated the effect of the CXCR2 antagonist AZD5069 on sputum neutrophil counts in adults with bronchiectasi...

A Randomised, Double-blind, Placebo-controlled Study of Escitalopram in Patients with Social Anxiety Disorder in Japan.

This randomised, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20mg/day) in Japanese patients with social anxiety disorder (SAD).

Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study.

To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA).

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial.

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counterac...

Clinical Trials [14012 Associated Clinical Trials listed on BioPortfolio]

A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Cystic Fibrosis

The purpose of this study is to investigate if treatment with AZD9668 for 28 days is effective in treating Cystic Fibrosis (CF) and if so how it compares to placebo (a substance which does...

A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis

The purpose of this study is to investigate if treatment with AZD9668 for 28 days is effective in treating Bronchiectasis (Brx) and if so how it compares to placebo (a substance which does...

Study of a Single Oral Dose of AZD9668 and Intra-venous (IV) Microdose of [C14] AZD9668 in Healthy Subjects

The primary objective of this study is to assess the absolute bioavailability and to evaluate pharmacokinetic parameters of a single oral dose and a radiolabelled intravenous microdose of ...

Single Oral Dose of 60 mg [14C]AZD9668 in Healthy Male Volunteers

The purpose of the study is to characterise the absorption, distribution, metabolism and excretion (ADME) of a single oral dose of [14C]AZD9668.

AZD9668 Relative Bioavailability

This clinical study will aid future formulation development and optimisation of AZD9668 tablets by evaluating possible effects of minor changes to the formulation and process on the rate a...

Medical and Biotech [MESH] Definitions

Radiotherapy where there is improved dose homogeneity within the tumor and reduced dosage to uninvolved structures. The precise shaping of dose distribution is achieved via the use of computer-controlled multileaf collimators.

The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)

The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.

Work consisting of a controlled study executed by several cooperating institutions.

Administration of the total dose of radiation (RADIATION DOSAGE) in parts, at timed intervals.

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topics

COPD (chronic obstructive pulmonary disease)
COPD (chronic obstructive pulmonary disease) is used for a number of conditions including chronic bronchitis and emphysema, which all  lead to the airways in the lungs becoming damaged and thus narrower,  making inhalation and exhalation harder...

Pulmonary
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Respiratory
Asthma COPD Cystic Fibrosis Pneumonia Pulmonary Medicine Respiratory Respiratory tract infections (RTIs) are any infection of the sinuses, throat, airways or lungs.  They're usually caused by viruses, but they can also ...


Searches Linking to this Article