Prednisolone Pharmacokinetics in Severe Asthma

NCT00662298 | Completed Phase 4 Results

• 2 other identifiers: 2007-002084-27REC ref number 07/H0801/119
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate whether severe asthmatic subjects have abnormal prednisolone absorption, and how this might affect the anti-inflammatory effects of prednisolone. The aims of the study are

1. 1.to compare the effect of high dose prednisolone on clinical and physiological responses
2. 2.to determine the effect of long-term oral prednisolone therapy on corticosteroid responsiveness and prednisolone pharmacokinetics
3. 3.to measure the effect of high dose prednisolone for 14 days on p38 MAPK activity, GR translocation and activation of NF-kB
4. 4.to validate an easier method of measuring corticosteroid insensitivity using whole blood, and a spot prednisolone serum level as a measure of adherence to prednisolone therapy

Conditions

Asthma

Keywords

severe asthma; prednisolone pharmacokinetics; anti-inflammatory effects

Outcome Measures

Primary Outcomes (3)

• Serum Prednisolone Levels Over 24 Hours

  2h, 6h, 24h

• Change in FEV1 24 Hours Post Prednisolone

  14 days

• Changes in eNO, Sputum Eosinophils and Inflammatory Mediators Over 24 Hours

  14 days

Secondary Outcomes (4)

• Difference Between Baseline and Day 14 in Serum Prednisolone Levels

  Baseline, 14 days

• Difference in FEV1 Between Day 1 and Day 14

  14 days

• Difference in Inflammatory Markers Between Day 1 and Day 14

  14 days

• Changes in Asthma Control Symptoms Before and After Treatment

  14 days

Study Arms (1)

Severe Asthma

EXPERIMENTAL

Drug: prednisolone

Interventions

prednisolone DRUG

40mg of prednisolone once a day for 14 days

Severe Asthma

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• for severe asthmatics:
• Physician diagnosis of asthma
• Aged 18 - 70
• Non-smokers or ex-smokers with less than 5 pack/year history
• Major characteristics (at least one of the following criteria)
• Treatment with continuous or near continuous (\>50% of year) oral corticosteroids
• Requirement for treatment with high dose inhaled corticosteroids (ICS)
• Minor characteristics (at least 2 out of the following)
• Requirement for daily treatment with a controller medication in addition to ICS e.g. LABA, theophylline, leukotriene antagonist
• Asthma symptoms requiring SABA on a daily or near daily basis
• Persistent airways obstruction (FEV1 \<80% predicted, diurnal PEF variation \>20%)
• One or more emergency care visits for asthma per year
• or more steroid "bursts" per year
• Prompt deterioration with ≤ 25% reduction in oral or ICS
• Near fatal asthma event in the past

You may not qualify if:

• Current smokers, or less than 3 years since quitting smoking
• Less than 4 weeks from an exacerbation
• Diabetes
• Active peptic ulceration
• Previous history of psychiatric disturbances on high dose prednisolone
• On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin
• Concomitant anti-IgE therapy
• Pregnancy

Sponsors & Collaborators

• Imperial College London: lead
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (1)

Asthma Laboratory, Royal Brompton Hospital

London, SW3 6LY, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Professor Fan Chung
• Organization: Imperial College London

f.chung@imperial.ac.uk

00442075947954

Study Officials

• Kian F Chung

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2008
• First Posted: April 21, 2008
• Study Start: June 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: November 20, 2019
• Results First Posted: November 20, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)