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

Primary Purpose

Bronchiectasis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD9668
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Bronchiectasis focused on measuring bronchiectasis, Phase II

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Female of non child bearing potential
  • Clinical diagnosis of bronchiectasis
  • Be sputum producers, with history of chronic expectoration on most days

Exclusion Criteria:

  • Concomitant diagnosis of pulmonary disease other than bronchiectasis or COPD
  • FEV1 of <30% of predicted normal

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AZD9668 active treatment

AZD9668 placebo treatment

Arm Description

Outcomes

Primary Outcome Measures

Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
24-hour Sputum Weight(g)
Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28
Slow Vital Capacity (SVC)
Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Forced Expiratory Volume in 1 Second (FEV1)
Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28
Forced Vital Capacity (FVC)
Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
FEF25-75% as a measure of lung function.Change from baseline to day 28
Morning Peak Expiratory Flow (PEF)
Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment
Evening Peak Expiratory Flow (PEF)
Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment
Bronkotest Diary Card Signs and Symptoms
The Bronkotest diary card includes 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). ANOVA models were fitted to compare the change from baseline between AZD9668 and placebo for each question separately, with a p-value of 0.1 considered statistically significant. The number of number of these 8 measures with significant differences is reported.
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). Change from baseline to day 28.

Secondary Outcome Measures

Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline

Full Information

First Posted
October 6, 2008
Last Updated
August 14, 2012
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00769119
Brief Title
A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis
Acronym
NEPAL
Official Title
A Phase II, Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy of 28 Day Oral Administration of AZD9668 in Patients With Bronchiectasis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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 not have any action).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiectasis
Keywords
bronchiectasis, Phase II

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD9668 active treatment
Arm Type
Experimental
Arm Title
AZD9668 placebo treatment
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
AZD9668
Intervention Description
2 x 30 mg, oral tablet, twice daily for 28 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
2 x Matched placebo, oral tablet, twice daily for 28 days
Primary Outcome Measure Information:
Title
Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
24-hour Sputum Weight(g)
Description
Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28
Time Frame
Baseline and day 28
Title
Slow Vital Capacity (SVC)
Description
Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Time Frame
Baseline and day 28
Title
Forced Expiratory Volume in 1 Second (FEV1)
Description
Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28
Time Frame
Baseline and day 28
Title
Forced Vital Capacity (FVC)
Description
Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Time Frame
Baseline and day 28
Title
Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
Description
FEF25-75% as a measure of lung function.Change from baseline to day 28
Time Frame
Baseline and day 28
Title
Morning Peak Expiratory Flow (PEF)
Description
Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment
Time Frame
Last 7 days on treatment
Title
Evening Peak Expiratory Flow (PEF)
Description
Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment
Time Frame
Last 7 days on treatment
Title
Bronkotest Diary Card Signs and Symptoms
Description
The Bronkotest diary card includes 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). ANOVA models were fitted to compare the change from baseline between AZD9668 and placebo for each question separately, with a p-value of 0.1 considered statistically significant. The number of number of these 8 measures with significant differences is reported.
Time Frame
Last 7 days on treatment
Title
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
Description
SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). Change from baseline to day 28.
Time Frame
Baseline and day 28
Secondary Outcome Measure Information:
Title
Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Description
Ratio of day 28 to baseline
Time Frame
Baseline and day 28
Title
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Description
Ratio of day 28 to baseline
Time Frame
Baseline and day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female of non child bearing potential Clinical diagnosis of bronchiectasis Be sputum producers, with history of chronic expectoration on most days Exclusion Criteria: Concomitant diagnosis of pulmonary disease other than bronchiectasis or COPD FEV1 of <30% of predicted normal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stockley, Prof
Organizational Affiliation
Queen Elizabeth Hospital, Birmingham, England
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carin Jorup
Organizational Affiliation
AstraZeneca R&D Lund
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Chemin Sainte-Foy
State/Province
Quebec
Country
Canada
Facility Name
Research Site
City
Calgary
Country
Canada
Facility Name
Research Site
City
Montreal
Country
Canada
Facility Name
Research Site
City
Ontario
Country
Canada
Facility Name
Research Site
City
Vancouver
Country
Canada
Facility Name
Research Site
City
Birmingham
Country
United Kingdom
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
New Castle
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23433769
Citation
Stockley R, De Soyza A, Gunawardena K, Perrett J, Forsman-Semb K, Entwistle N, Snell N. Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis. Respir Med. 2013 Apr;107(4):524-33. doi: 10.1016/j.rmed.2012.12.009. Epub 2013 Feb 20.
Results Reference
derived

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

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