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.
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.
1Universitätsklinikum Giessen und Marburg, Marburg, Germany.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22458939
- DOI: http://dx.doi.org/10.3109/15412555.2011.641803
This double-blind, placebo-controlled, dose-finding phase IIb study evaluated the efficacy and safety of ponesimod, an oral selective S1P1 receptor modulator, for the treatment of patients with relaps...
The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery ...
Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid dependent subjects. The objectives of this Phase I ...
Effects of low-dose versus placebo or conventional dose postmenopausal hormone therapy on variables related to cardiovascular risk: a systematic review and meta-analyses of randomized clinical trials.
Context: Hormone therapy (HT), the most efficient treatment for menopausal symptoms, might have deleterious cardiovascular (CV) effects. Objective: To evaluate the effects of low-dose estrogen HT on C...
Homozygous familial hypercholesterolaemia is a rare, serious disorder caused by very low or absent plasma clearance of LDL, substantially raised LDL cholesterol, and accelerated development of cardiov...
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...
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...
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 ...
The purpose of the study is to characterise the absorption, distribution, metabolism and excretion (ADME) of a single oral dose of [14C]AZD9668.
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.