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

A Phase 2 study testing AZD9668 in people with Cystic Fibrosis, run by AstraZeneca at 14 sites in 6 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 Cystic Fibrosis (CF) 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 16 years and older
Conditions the study is for: Cystic Fibrosis
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: 56 participants
Where: 14 sitesin 6 countries
Study dates: Oct 2008to Aug 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 16 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Male or post-menopausal or surgically sterile female patients
Have a clinical diagnosis of Cystic Fibrosis with lung function tests greater or equal to 40% of normal
Have normal renal function

Who cannot join

Lung transplant patients
Significant liver disease
Any other non-CF-related lung disease that may interfere with study assessments

Trial locations and contacts

14 sites in 6 countries.

Country

City, postcode or hospital

14 sites in 6 countries

Germany4 sites

Research Site
Hamburg
Research Site
Kiel
Research Site
Leipzig
Research Site
München

Other trials in Germany

Sweden4 sites

Research Site
Gothenburg
Research Site
Lund
Research Site
Stockholm
Research Site
Uppsala

Other trials in Sweden

Poland2 sites

Research Site
Rabka-Zdrój
Research Site
Warsaw

Other trials in Poland

United Kingdom2 sites

Research Site
Belfast, Northern Ireland
Research Site
Liverpool

Other trials in United Kingdom

Denmark1 site

Research Site
Copenhagen

Other trials in Denmark

Russia1 site

Research Site
Moscow

Other trials in Russia

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 Cystic Fibrosis

Conditions: Cystic Fibrosis
Being tested: AZD9668, AZD9668 Placebo equivalent
Keywords: cystic fibrosis
Medical subject headings: Cystic Fibrosis

What participants receive

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

AZD9668Drug
60 mg, oral tablet, twice daily for 28 days
AZD9668 Placebo equivalentDrug
Match placebo to 60 mg, oral tablet, twice daily for 28 days

Study groups in NCT00757848
Study group	Role	What they receive
AZD9668	Experimental	Not described Receives: Drug: AZD9668
Placebo	Placebo comparator	Not described Receives: Drug: AZD9668 Placebo equivalent

What is being measured

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

Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: Baseline and Values from day 21 to 28
Sputum Percentage Neutrophil Count
Percentage of neutrophils in white blood cell count.Change from Baseline (mean of 2 baseline visits) to the end of the treatment period (mean of 2 visits at the end of the treatment)
Measured: Baseline and Values from day 21 to 28
24-hour Sputum Weight
Sputum weight (g) collected during 24 hour periods. 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
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 Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
FEF25-75% (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
Morning Peak Expiratory Flow (PEF)
Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from 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 baseline value to mean of the last 7 days on treatment
Measured: 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.
Measured: The last 7 days on treatment
Cystic Fibrosis Questionnaire (CFQ-R) - Quittner
Cystic Fibrosis Questionnaire Overall Score as a measure of quality of life and disease symptoms. Scores range from 0 to 100, with higher scores indicating better health. The overall score is the sum of 12 subscores. Change from baseline to day 28.
Measured: Baseline and day 28

Secondary outcomes (9)

Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.Values from day 21 to 28
Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.
Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.
Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Measured: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 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.

Oct 2008Aug 2009

First posted23 Sep 2008 (estimated)
Study startOct 2008
Primary completionAug 2009
Study completionAug 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 Cystic FibrosisStudies 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: 56 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00757848
Sponsor's protocol ID: D0520C00009
Acronym: INCA
Status last verified: Aug 2012
First submitted: 22 Sep 2008
Last updated: 20 Aug 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur Respir J. 2012 Oct;40(4):969-76. doi: 10.1183/09031936.00194611. Epub 2012 Jan 20.
PubMed 22267768

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 Cystic Fibrosis 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 Cystic Fibrosis
ClinicalTrials.gov ID: NCT00757848
Acronym / sponsor ID: INCA / D0520C00009
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 56 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Oct 2008
Primary completion: Aug 2009 (actual)
Study completion: Aug 2009 (actual)
First posted: 23 Sep 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	Experimental	Drug: AZD9668
Placebo	Placebo comparator	Drug: AZD9668 Placebo equivalent

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (3 listed)

Male or post-menopausal or surgically sterile female patients
Have a clinical diagnosis of Cystic Fibrosis with lung function tests greater or equal to 40% of normal
Have normal renal function

Key exclusion criteria (3 listed)

Lung transplant patients
Significant liver disease
Any other non-CF-related lung disease that may interfere with study assessments

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
AZD966860 mg, oral tablet, twice daily for 28 days	Drug	AZD9668
AZD9668 Placebo equivalentMatch placebo to 60 mg, oral tablet, twice daily for 28 days	Drug	Placebo

Primary outcome

Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline
Time frame: Baseline and Values from day 21 to 28
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Sputum Percentage Neutrophil Count
Time frame: Baseline and Values from day 21 to 28
Percentage of neutrophils in white blood cell count.Change from Baseline (mean of 2 baseline visits) to the end of the treatment period (mean of 2 visits at the end of the treatment)
24-hour Sputum Weight
Time frame: Baseline and day 28
Sputum weight (g) collected during 24 hour periods. 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.
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 Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
Time frame: Baseline and day 28
FEF25-75% (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.
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 baseline value to mean of the last 7 days on treatment
Evening Peak Expiratory Flow (PEF)
Time frame: The last 7 days on treatment
Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from baseline value to mean of the last 7 days on treatment
Bronkotest Diary Card Signs and Symptoms
Time frame: The 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.
Cystic Fibrosis Questionnaire (CFQ-R) - Quittner
Time frame: Baseline and day 28
Cystic Fibrosis Questionnaire Overall Score as a measure of quality of life and disease symptoms. Scores range from 0 to 100, with higher scores indicating better health. The overall score is the sum of 12 subscores. Change from baseline to day 28.

9 secondary outcomes

Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.Values from day 21 to 28
Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.
Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.
Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Time frame: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 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	27	24
Placebo	29	27

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

Time frame: Baseline and Values from day 21 to 28. Least squares mean (95% Confidence Interval). Unit: ratio

Measure	AZD9668 n = 24	Placebo n = 28
Value	1.07 (0.82 to 1.40)	1.10 (0.86 to 1.41)

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: Sputum Percentage Neutrophil Count

Time frame: Baseline and Values from day 21 to 28. Least squares mean (Standard Error). Unit: percentage of neutrophils in WBCs

Measure	AZD9668 n = 24	Placebo n = 28
Value	3.21 (1.757)	1.96 (1.566)

Primary outcome: 24-hour Sputum Weight

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

Measure	AZD9668 n = 24	Placebo n = 27
Value	-2.29 (2.261)	-5.13 (2.178)

Primary outcome: Forced Expiratory Volume in 1 Second (FEV1)

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

Measure	AZD9668 n = 24	Placebo n = 29
Value	-0.02 (0.048)	0.01 (0.043)

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 26 (0%)	16 of 26 (61.5%)	Not reported
Placebo	2 of 29 (6.9%)	22 of 29 (75.9%)	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 22267768Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur Respir J. 2012 Oct;40(4):969-76. doi: 10.1183/09031936.00194611. Epub 2012 Jan 20.

Related trials for Cystic Fibrosis

RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
Active, not recruiting
Personalized Mobile Health Platform to Promote Physical Activity in Adolescents and Young Adults With Cystic Fibrosis
Cystic Fibrosis (CF)
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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.

Prof. Elborn principal investigator

Belfast hospital

Joanna Marks-Konczalik study director

AstraZeneca

14 sites in 6 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 Cystic Fibrosis, run by AstraZeneca at 14 sites in 6 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 3 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 14 sites in Germany, Sweden, Poland, United Kingdom, Denmark and 1 more country. 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 Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline (time frame: Baseline and Values from day 21 to 28). 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 NCT00757848, 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.