BronchiectasisPhase 2NEPALNCT00769119

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

A Phase 2 study testing AZD9668 in people with Bronchiectasis, run by AstraZeneca at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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). Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Bronchiectasis
What is being tested?: AZD9668
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: 9 sitesin 2 countries
Study dates: Sep 2008to Apr 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

Canada5 sites

Research Site
Calgary
Research Site
Chemin Sainte-Foy, Quebec
Research Site
Montreal
Research Site
Ontario
Research Site
Vancouver

Other trials in Canada

United Kingdom4 sites

Research Site
Birmingham
Research Site
Cambridge
Research Site
London
Research Site
Newcastle

Other trials in United Kingdom

About this study

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

Conditions: Bronchiectasis
Being tested: AZD9668, Placebo
Keywords: bronchiectasis, Phase II
Medical subject headings: Bronchiectasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD9668Drug
2 x 30 mg, oral tablet, twice daily for 28 days
PlaceboDrug
2 x Matched placebo, oral tablet, twice daily for 28 days

Study groups in NCT00769119
Study group	Role	What they receive
AZD9668 active treatment	Experimental	Not described Receives: Drug: AZD9668
AZD9668 placebo treatment	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: Baseline and day 28
Slow Vital Capacity (SVC)
Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Measured: 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
Measured: Baseline and day 28
Forced Vital Capacity (FVC)
Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: Baseline and day 28

Secondary outcomes (9)

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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Measured: 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
Measured: Baseline and day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2008Apr 2009

First posted8 Oct 2008 (estimated)
Study startSep 2008
Primary completionApr 2009
Study completionApr 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for BronchiectasisStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00769119
Sponsor's protocol ID: D0520C00010
Acronym: NEPAL
Status last verified: Aug 2012
First submitted: 6 Oct 2008
Last updated: 20 Aug 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 23433769

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bronchiectasis trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00769119
Acronym / sponsor ID: NEPAL / D0520C00010
Conditions: Bronchiectasis
Keywords: bronchiectasis, Phase II
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Sep 2008
Primary completion: Apr 2009 (actual)
Study completion: Apr 2009 (actual)
First posted: 8 Oct 2008 (estimated)
Results: Posted 25 Jul 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
AZD9668 active treatment	Experimental	Drug: AZD9668
AZD9668 placebo treatment	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (2 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD96682 x 30 mg, oral tablet, twice daily for 28 days	Drug	AZD9668 active treatment
Placebo2 x Matched placebo, oral tablet, twice daily for 28 days	Drug	AZD9668 placebo treatment

Primary outcome

Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
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
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
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)
Time frame: Baseline and day 28
Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28
Slow Vital Capacity (SVC)
Time frame: Baseline and day 28
Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28
Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline and day 28
Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28
Forced Vital Capacity (FVC)
Time frame: Baseline and day 28
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%)
Time frame: Baseline and day 28
FEF25-75% as a measure of lung function.Change from baseline to day 28
Morning Peak Expiratory Flow (PEF)
Time frame: Last 7 days on treatment
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)
Time frame: Last 7 days on treatment
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
Time frame: Last 7 days on treatment
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)
Time frame: Baseline and day 28
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.

9 secondary outcomes

Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Time frame: Baseline and day 28
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Time frame: Baseline and day 28

Results and safety

Results posted to the registry on 25 Jul 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD9668	22	20
Placebo	16	13

Primary outcome: Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline

Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.. Least squares mean (95% Confidence Interval). Unit: ratio

Measure	AZD9668 n = 18	Placebo n = 10
Value	1.08 (0.60 to 1.72)	1.01 (0.73 to 1.60)

Population analysed: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

Primary outcome: Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline

Time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.. Least squares mean (95% Confidence Interval). Unit: ratio

Measure	AZD9668 n = 18	Placebo n = 10
Value	1.12 (1.02 to 1.21)	1.04 (0.92 to 1.16)

Primary outcome: 24-hour Sputum Weight(g)

Time frame: Baseline and day 28. Least squares mean (Standard Error). Unit: g

Measure	AZD9668 n = 20	Placebo n = 13
Value	-0.15 (4.376)	-5.37 (3.455)

Primary outcome: Slow Vital Capacity (SVC)

Time frame: Baseline and day 28. Least squares mean (Standard Error). Unit: L

Measure	AZD9668 n = 20	Placebo n = 13
Value	0.07 (0.045)	-0.07 (0.057)

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD9668	0 of 22 (0%)	13 of 22 (59.1%)	Not reported
Placebo	0 of 16 (0%)	15 of 16 (93.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23433769Stockley 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.

Related trials for Bronchiectasis

RecruitingPhase 1
Investigation of Pharmacokinetics, Safety of HSK31858 in Subjects With Renal Impairment
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RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stockley, Prof principal investigator

Queen Elizabeth Hospital, Birmingham, England

Carin Jorup study director

AstraZeneca R&D Lund

9 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD9668 in people with Bronchiectasis, run by AstraZeneca at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline (time frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00769119, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2012; AzTrials last refreshed its copy on 5 Nov 2026.