Effect of Symbicort on GR Localisation in Asthma

NCT00159263 | Completed Results

• 1 other identifier: BU-039-0005
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate a possible interaction between formoterol and budesonide on GR-translocation and to compare the effect of different doses of Symbicort (80/4.5 and 2x80/4.5 mcg) with the effect of budesonide (200 mcg and 800 mcg) on GR translocation, and to investigate the effect of the study drugs on exhaled NO (bronchial and alveolar fraction.

Conditions

Asthma

Keywords

Asthma; Glucocorticoid; Long-acting beta2-adrenoceptor; Inhaled corticosteroids

Outcome Measures

Primary Outcomes (3)

• Changes in GR-GRE Binding

  The GR-GRE binding is the glucocorticoid receptor (GR) DNA binding affinity. GR-GRE activity as assed by enzyme-immunosorbent assay

  1-2h

• Changes in MKP-1 mRNA

  Changes in MKP-1 mRNA measured by PCR

  1-2h

• IL8 mRNA

  Measured by PCR

  1-2h

Study Arms (6)

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebos

Formoterol

EXPERIMENTAL

Oxis(®) 12 μg

Drug: Formoterol Inhalant Powder

Budesonide low dose

EXPERIMENTAL

Pulmicort(®) 200 μg

Drug: Budesonide Powder

Budesonide high dose

EXPERIMENTAL

Pulmicort(®) 800 μg

Drug: Budesonide Powder

Budesonide/formoterol combination single

EXPERIMENTAL

single 100/6 μg SYM100

Drug: Budesonide and Formoterol Product

Budesonide/formoterol combination double

EXPERIMENTAL

double 200/12 μg SYM200

Drug: Budesonide and Formoterol Product

Interventions

Placebos DRUG

Dry powder inhaler

Placebo

Formoterol Inhalant Powder DRUG

12ug

Also known as: Oxis

Formoterol

Budesonide Powder DRUG

Inhaler

Also known as: Pulmicort

Budesonide high dose; Budesonide low dose

Budesonide and Formoterol Product DRUG

Combination Inhaler, Symbicort

Also known as: Combination Inhaler, Symbicort

Budesonide/formoterol combination double; Budesonide/formoterol combination single

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with mild steroid-naïve asthma (ATS criteria) of either sex with FEV1 \>70 % pred
• Able to produce sputum after sputum induction
• Exhaled NO (flow 50 ml/s) ≥ 20 ppb
• Written informed consent

You may not qualify if:

• Current upper respiratory tract infections
• Use of inhaled and/or oral GCS within 4 weeks prior to visit 1
• Treatment with antileukotrienes, theophylline, tiotropium and ipratropium within 2 weeks prior to screening visit
• Hypersensitivity to any of the investigational drugs or lactose
• Use of any beta blocking agent (including eye-drops)
• Women who are pregnant, breast-feeding or planning a pregnancy during the study. Women must be postmenopausal (at least one year must have passed after the last menstruation), surgically sterile or using acceptable contraceptives, as judged by the investigator
• Any significant disease or disorder (e.g. cardiovascular, pulmonary (other than asthma), gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subjects ability to participate in the study
• Inability to tolerate temporary withdrawal of bronchodilatory therapy
• Subjects not considered capable, as judged by the investigator, of following instructions of the study, e.g. because of a history of alcohol or drug abuse or any other reason
• Previous randomization in this study

Sponsors & Collaborators

• Imperial College London: lead
• AstraZeneca: collaborator

Study Sites (1)

Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital

London, United Kingdom

Location

Related Publications (1)

• Essilfie-Quaye S, Ito K, Ito M, Kharitonov SA, Barnes PJ. Comparison of Symbicort(R) versus Pulmicort(R) on steroid pharmacodynamic markers in asthma patients. Respir Med. 2011 Dec;105(12):1784-9. doi: 10.1016/j.rmed.2011.08.020. Epub 2011 Sep 7.

  PMID: 21903370 RESULT

MeSH Terms

Conditions

Asthma

Interventions

Formoterol Fumarate; Budesonide; Budesonide, Formoterol Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Peter Barnes
• Organization: Imperial College London

p.j.barnes@imperial.ac.uk

+44 (0)20 7594 7959

Study Officials

• Sergei A Kharitonov, MD PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: November 1, 2004
• Primary Completion: November 1, 2006
• Study Completion: November 1, 2006
• Last Updated: September 27, 2019
• Results First Posted: September 27, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)