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

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

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).

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Drug: AZD9668; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada
    • Research Site
  • Montreal, Canada
    • Research Site
  • Ontario, Canada
    • Research Site
  • Vancouver, Canada
    • Research Site
  • Quebec
    • Chemin Sainte-Foy, Quebec, Canada
      • Research Site
• United Kingdom
  • Birmingham, United Kingdom
    • Research Site
  • Cambridge, United Kingdom
    • Research Site
  • London, United Kingdom
    • Research Site
  • New Castle, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD9668 active treatment	Drug: AZD9668; 2 x 30 mg, oral tablet, twice daily for 28 days
Placebo Comparator: AZD9668 placebo treatment	Drug: Placebo; 2 x Matched placebo, oral tablet, twice daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
24-hour Sputum Weight(g)	Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28	Baseline and day 28
Slow Vital Capacity (SVC)	Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28	Baseline and 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	Baseline and day 28
Forced Vital Capacity (FVC)	Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28	Baseline and 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	Baseline and 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	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	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.	Last 7 days on treatment
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.	Baseline and day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline	Ratio of day 28 to baseline	Baseline and day 28
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline	Ratio of day 28 to baseline	Baseline and day 28
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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Stockley, Prof, Queen Elizabeth Hospital, Birmingham, England; Study Director: Carin Jorup, AstraZeneca R&D Lund

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Estimate): August 20, 2012
• Last Update Submitted That Met QC Criteria: August 14, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Phase II; bronchiectasis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: D0520C00010