A Phase II , Placebo-controlled Study to Assess Efficacy... | NCT00769119

Status Module

Label	Type	Description	Intervention Names
AZD9668 active treatment	Experimental		Drug: AZD9668
AZD9668 placebo treatment	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AZD9668	Drug	2 x 30 mg, oral tablet, twice daily for 28 days	AZD9668 active treatment

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
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

Name	Affiliation	Role
Stockley, Prof	Queen Elizabeth Hospital, Birmingham, England	Principal Investigator
Carin Jorup	AstraZeneca R&D Lund	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Chemin Sainte-Foy	Quebec		Canada
Research Site

PubMed Identifier	Type	Citation	Retractions
23433769	Derived	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 Section

Participant Flow Module

ID	Title	Description
FG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
FG001	Placebo	Placebo, 2 tablets twice daily (bid)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
BG001	Placebo	Placebo, 2 tablets twice daily (bid)
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00022 BG00116 BG00238

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG00018 OG00110

Title

Denominators

Categories

Title	Measurements
	OG0001.08(0.60 to 1.72) OG0011.01(0.73 to 1.60)

Primary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

24-hour Sputum Weight(g)

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

Posted

Least Squares Mean

Standard Error

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

Slow Vital Capacity (SVC)

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

Posted

Least Squares Mean

Standard Error

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

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

Posted

Least Squares Mean

Standard Error

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

Forced Vital Capacity (FVC)

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

Posted

Least Squares Mean

Standard Error

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

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

Posted

Least Squares Mean

Standard Error

L/s

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

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

Posted

Least Squares Mean

Standard Error

L/min

Last 7 days on treatment

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

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

Posted

Least Squares Mean

Standard Error

L/min

Last 7 days on treatment

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Primary

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.

Posted

Number

events

Last 7 days on treatment

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants

Primary

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.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

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

Posted

Least Squares Mean

95% Confidence Interval

ratio

End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline

Ratio of day 28 to baseline

Posted

Least Squares Mean

95% Confidence Interval

ratio

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Secondary

Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline

Ratio of day 28 to baseline

Posted

Least Squares Mean

95% Confidence Interval

ratio

Baseline and day 28

ID	Title	Description
OG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)
OG001	Placebo	Placebo, 2 tablets twice daily (bid)

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected22 at risk EG0014 affected16 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0012 affected16 at risk
Abdominal Distension	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Oedema Peripheral	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0012 affected16 at risk
Chest Discomfort	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Fatigue	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Local Swelling	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Nasopharyngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0004 affected22 at risk EG0010 affected16 at risk
Influenza	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Sinusitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0002 affected22 at risk EG0011 affected16 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Thermal Burn	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Increased Appetite	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected22 at risk EG0010 affected16 at risk
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected22 at risk EG0011 affected16 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Musculoskeletal Discomfort	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0007 affected22 at risk EG0013 affected16 at risk
Dizziness	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Lethargy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Tremor	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Depressed Mood	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Sleep Disorder	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Erectile Dysfunction	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0012 affected16 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected16 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk
Hyperaemia	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected16 at risk

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AZD9668	AZD9668, 2 x 30 mg twice daily (bid)			0	22	13	22
EG001	Placebo	Placebo, 2 tablets twice daily (bid)			0	16	15	16