Trial Outcomes & Findings for A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Cystic Fibrosis (NCT NCT00757848)

NCT ID: NCT00757848

Last Updated: 2012-08-20

Results Overview

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 56 participants
• Primary outcome timeframe: Baseline and Values from day 21 to 28
• Results posted on: 2012-08-20

Participant Flow

First patient enrolled 30 October 2008. Last patient completed 04 August 2009. Study conducted at 15 centres in 6 countries (UK, Germany, Sweden, Poland, Denmark, Russia).

Participant milestones

Measure	AZD9668 AZD9668, 2 x 30 mg twice daily (bid)	Placebo Placebo, 2 tablets twice daily (bid)
Overall Study STARTED	27	29
Overall Study COMPLETED	24	27
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Measure	AZD9668 AZD9668, 2 x 30 mg twice daily (bid)	Placebo Placebo, 2 tablets twice daily (bid)
Overall Study Voluntary discontinuation	1	0
Overall Study Adverse Event	1	2
Overall Study Incorrect enrolment	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD9668 n=25 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)	Total n=54 Participants Total of all reporting groups
Age Continuous	25 years n=5 Participants	25 years n=7 Participants	25 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	29 Participants n=7 Participants	53 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Values from day 21 to 28

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline	1.07 ratio Interval 0.82 to 1.4	1.10 ratio Interval 0.86 to 1.41

PRIMARY outcome

Timeframe: Baseline and Values from day 21 to 28

Population: 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.

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)

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Sputum Percentage Neutrophil Count	3.21 percentage of neutrophils in WBCs Standard Error 1.757 • Interval 1.757 to	1.96 percentage of neutrophils in WBCs Standard Error 1.566 • Interval 1.566 to

PRIMARY outcome

Timeframe: Baseline and day 28

Population: 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.

Sputum weight (g) collected during 24 hour periods. Change from Baseline to day 28.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=27 Participants Placebo, 2 tablets twice daily (bid)
24-hour Sputum Weight	-2.29 grams Standard Error 2.261 • Interval 2.261 to	-5.13 grams Standard Error 2.178 • Interval 2.178 to

PRIMARY outcome

Timeframe: Baseline and day 28

Population: 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.

Forced Expiratory Volume in 1 second (L) as a measure of lung function.Change from Baseline to day 28.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)
Forced Expiratory Volume in 1 Second (FEV1)	-0.02 L Standard Error 0.048 • Interval 0.048 to	0.01 L Standard Error 0.043 • Interval 0.043 to

PRIMARY outcome

Timeframe: Baseline and day 28

Population: 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.

Slow Vital capacity (L) as a measure of lung function. Change from Baseline to day 28.

Outcome measures

Measure	AZD9668 n=20 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=27 Participants Placebo, 2 tablets twice daily (bid)
Slow Vital Capacity (SVC)	-0.03 L Standard Error 0.106 • Interval 0.106 to	-0.15 L Standard Error 0.081 • Interval 0.081 to

PRIMARY outcome

Timeframe: Baseline and day 28

Population: 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.

FEF25-75% (L) as a measure of lung function. Change from Baseline to day 28.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)
Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)	-0.07 L Standard Error 0.090 • Interval 0.09 to	0.08 L Standard Error 0.082 • Interval 0.082 to

PRIMARY outcome

Timeframe: Baseline and day 28

Population: 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.

Forced Vital Capacity (L) as a measure of lung function. Change from Baseline to day 28.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)
Forced Vital Capacity (FVC)	-0.06 L Standard Error 0.066 • Interval 0.066 to	0.01 L Standard Error 0.059 • Interval 0.059 to

PRIMARY outcome

Timeframe: Last 7 days on treatment

Population: 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.

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

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)
Morning Peak Expiratory Flow (PEF)	-1.17 L/min Standard Error 8.055 • Interval 8.055 to	14.05 L/min Standard Error 7.262 • Interval 7.262 to

PRIMARY outcome

Timeframe: The last 7 days on treatment

Population: 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.

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

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)
Evening Peak Expiratory Flow (PEF)	0.59 L/min Standard Error 6.874 • Interval 6.874 to	6.32 L/min Standard Error 6.194 • Interval 6.194 to

PRIMARY outcome

Timeframe: The last 7 days on treatment

Population: 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.

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.

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 Participants Placebo, 2 tablets twice daily (bid)
Bronkotest Diary Card Signs and Symptoms	0 Signs and Symptoms	0 Signs and Symptoms

PRIMARY outcome

Timeframe: Baseline and day 28

Population: 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.

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.

Outcome measures

Measure	AZD9668 n=20 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=27 Participants Placebo, 2 tablets twice daily (bid)
Cystic Fibrosis Questionnaire (CFQ-R) - Quittner	-19.7 units on a scale Standard Error 18.12 • Interval 18.12 to	4.7 units on a scale Standard Error 14.93 • Interval 14.93 to

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.Values from day 21 to 28

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline	0.91 ratio Interval 0.69 to 1.2	1.24 ratio Interval 0.97 to 1.6

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline	0.71 ratio Interval 0.56 to 0.9	1.20 ratio Interval 0.96 to 1.48

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline	0.95 ratio Interval 0.75 to 1.22	1.09 ratio Interval 0.87 to 1.36

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline	0.91 ratio Interval 0.74 to 1.12	1.18 ratio Interval 0.98 to 1.42

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=28 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline	0.73 ratio Interval 0.6 to 0.88	0.91 ratio Interval 0.76 to 1.08

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=26 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline	0.86 ratio Interval 0.71 to 1.05	1.04 ratio Interval 0.86 to 1.26

SECONDARY outcome

Timeframe: End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Population: 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.

Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

Outcome measures

Measure	AZD9668 n=24 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=25 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline	1.02 ratio Interval 0.87 to 1.19	1.00 ratio Interval 0.86 to 1.17

SECONDARY outcome

Timeframe: Baseline and day 28

Population: 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.

Ratio of day 28 to baseline

Outcome measures

Measure	AZD9668 n=21 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=25 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline	0.88 ratio Interval 0.76 to 1.03	1.27 ratio Interval 1.08 to 1.48

SECONDARY outcome

Timeframe: Baseline and day 28

Population: 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.

Ratio of day 28 to baseline

Outcome measures

Measure	AZD9668 n=22 Participants AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=27 Participants Placebo, 2 tablets twice daily (bid)
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline	0.68 ratio Interval 0.53 to 0.87	0.97 ratio Interval 0.78 to 1.22

Adverse Events

AZD9668

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD9668 n=26 participants at risk AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 participants at risk Placebo, 2 tablets twice daily (bid)
Infections and infestations Pneumonia	0.00% 0/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	3.4% 1/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	0.00% 0/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	3.4% 1/29 Safety analysis set - one patient not included as he/she did not receive any study drug.

Other adverse events

Measure	AZD9668 n=26 participants at risk AZD9668, 2 x 30 mg twice daily (bid)	Placebo n=29 participants at risk Placebo, 2 tablets twice daily (bid)
Gastrointestinal disorders Constipation	0.00% 0/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	6.9% 2/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	6.9% 2/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
General disorders Non-Cardiac Chest Pain	0.00% 0/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	6.9% 2/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
General disorders Pyrexia	0.00% 0/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	6.9% 2/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Infections and infestations Nasopharyngitis	11.5% 3/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	10.3% 3/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Musculoskeletal and connective tissue disorders Back Pain	3.8% 1/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	6.9% 2/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Nervous system disorders Headache	30.8% 8/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	24.1% 7/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 2/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	3.4% 1/29 Safety analysis set - one patient not included as he/she did not receive any study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	7.7% 2/26 Safety analysis set - one patient not included as he/she did not receive any study drug.	3.4% 1/29 Safety analysis set - one patient not included as he/she did not receive any study drug.

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place