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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00757848
• Collaborator: (none)
• Enrollment: 56
• Locations: 14
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: AZD9668; Drug: AZD9668 Placebo equivalent	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• 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
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD9668	Drug: AZD9668; 60 mg, oral tablet, twice daily for 28 days
Placebo Comparator: Placebo	Drug: AZD9668 Placebo equivalent; Match placebo to 60 mg, oral tablet, twice daily for 28 days

Outcome Measures

Primary Outcome Measures

1. Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline [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

2. Sputum Percentage Neutrophil Count [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)

3. 24-hour Sputum Weight [Baseline and day 28]

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

4. Forced Expiratory Volume in 1 Second (FEV1) [Baseline and day 28]

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

5. Slow Vital Capacity (SVC) [Baseline and day 28]

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

6. Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) [Baseline and day 28]

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

7. Forced Vital Capacity (FVC) [Baseline and day 28]

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

8. Morning Peak Expiratory Flow (PEF) [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

9. Evening Peak Expiratory Flow (PEF) [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

10. Bronkotest Diary Card Signs and Symptoms [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.

11. Cystic Fibrosis Questionnaire (CFQ-R) - Quittner [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.

Secondary Outcome Measures

1. Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline [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 the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits

2. Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline [End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.]

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

3. Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline [End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits]

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

4. Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline [End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.]

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

5. Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline [End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits]

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

6. Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline [End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits]

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

7. Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline [End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits]

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

8. Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline [Baseline and day 28]

   Ratio of day 28 to baseline

9. Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline [Baseline and day 28]

   Ratio of day 28 to baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• Lung transplant patients

• Significant liver disease

• Any other non-CF-related lung disease that may interfere with study assessments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Kobenhavn		Denmark
2	Research Site	Hamburg		Germany
3	Research Site	Kiel		Germany
4	Research Site	Leipzig		Germany
5	Research Site	Munchen		Germany
6	Research Site	Rabka-zdroj		Poland
7	Research Site	Warszawa		Poland
8	Research Site	Moscow		Russian Federation
9	Research Site	Goteborg		Sweden
10	Research Site	Lund		Sweden
11	Research Site	Stockholm		Sweden
12	Research Site	Uppsala		Sweden
13	Research Site	Belfast	Northern Ireland	United Kingdom
14	Research Site	Liverpool		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Prof. Elborn, Belfast hospital
• Study Director: Joanna Marks-Konczalik, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00757848
• Other Study ID Numbers: D0520C00009
• First Posted: Sep 23, 2008
• Last Update Posted: Aug 20, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by AstraZeneca: cystic fibrosis
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details	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).

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Period Title: Overall Study
STARTED	27	29
COMPLETED	24	27
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	AZD9668	Placebo	Total
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)	Total of all reporting groups
Overall Participants	25	29	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	25	25	25
Sex: Female, Male (Count of Participants)
Female	1 4%	0 0%	1 1.9%
Male	24 96%	29 100%	53 98.1%

Outcome Measures

1. Primary Outcome

Title	Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	Baseline and Values from day 21 to 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (95% Confidence Interval) [ratio]	1.07	1.10

2. Primary Outcome

Title	Sputum Percentage Neutrophil Count
Description	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)
Time Frame	Baseline and Values from day 21 to 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (Standard Error) [percentage of neutrophils in WBCs]	3.21 (1.757)	1.96 (1.566)

3. Primary Outcome

Title	24-hour Sputum Weight
Description	Sputum weight (g) collected during 24 hour periods. Change from Baseline to day 28.
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	27
Least Squares Mean (Standard Error) [grams]	-2.29 (2.261)	-5.13 (2.178)

4. Primary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1)
Description	Forced Expiratory Volume in 1 second (L) as a measure of lung function.Change from Baseline to day 28.
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	29
Least Squares Mean (Standard Error) [L]	-0.02 (0.048)	0.01 (0.043)

5. Primary Outcome

Title	Slow Vital Capacity (SVC)
Description	Slow Vital capacity (L) as a measure of lung function. Change from Baseline to day 28.
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	20	27
Least Squares Mean (Standard Error) [L]	-0.03 (0.106)	-0.15 (0.081)

6. Primary Outcome

Title	Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
Description	FEF25-75% (L) as a measure of lung function. Change from Baseline to day 28.
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	29
Least Squares Mean (Standard Error) [L]	-0.07 (0.090)	0.08 (0.082)

7. Primary Outcome

Title	Forced Vital Capacity (FVC)
Description	Forced Vital Capacity (L) as a measure of lung function. Change from Baseline to day 28.
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	29
Least Squares Mean (Standard Error) [L]	-0.06 (0.066)	0.01 (0.059)

8. Primary Outcome

Title	Morning Peak Expiratory Flow (PEF)
Description	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
Time Frame	Last 7 days on treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	29
Least Squares Mean (Standard Error) [L/min]	-1.17 (8.055)	14.05 (7.262)

9. Primary Outcome

Title	Evening Peak Expiratory Flow (PEF)
Description	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
Time Frame	The last 7 days on treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	29
Least Squares Mean (Standard Error) [L/min]	0.59 (6.874)	6.32 (6.194)

10. Primary Outcome

Title	Bronkotest Diary Card Signs and Symptoms
Description	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.
Time Frame	The last 7 days on treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	29
Number [Signs and Symptoms]	0	0

11. Primary Outcome

Title	Cystic Fibrosis Questionnaire (CFQ-R) - Quittner
Description	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.
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	20	27
Least Squares Mean (Standard Error) [units on a scale]	-19.7 (18.12)	4.7 (14.93)

12. Secondary Outcome

Title	Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (95% Confidence Interval) [ratio]	0.91	1.24

13. Secondary Outcome

Title	Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (95% Confidence Interval) [ratio]	0.71	1.20

14. Secondary Outcome

Title	Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (95% Confidence Interval) [ratio]	0.95	1.09

15. Secondary Outcome

Title	Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (95% Confidence Interval) [ratio]	0.91	1.18

16. Secondary Outcome

Title	Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	28
Least Squares Mean (95% Confidence Interval) [ratio]	0.73	0.91

17. Secondary Outcome

Title	Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	26
Least Squares Mean (95% Confidence Interval) [ratio]	0.86	1.04

18. Secondary Outcome

Title	Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Description	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	24	25
Least Squares Mean (95% Confidence Interval) [ratio]	1.02	1.00

19. Secondary Outcome

Title	Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Description	Ratio of day 28 to baseline
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	21	25
Least Squares Mean (95% Confidence Interval) [ratio]	0.88	1.27

20. Secondary Outcome

Title	Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Description	Ratio of day 28 to baseline
Time Frame	Baseline and day 28

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)	Placebo, 2 tablets twice daily (bid)
Measure Participants	22	27
Least Squares Mean (95% Confidence Interval) [ratio]	0.68	0.97

Adverse Events

Adverse Event Reporting Description	Safety analysis set - one patient not included as he/she did not receive any study drug.
Arm/Group Title	AZD9668		Placebo
Arm/Group Description	AZD9668, 2 x 30 mg twice daily (bid)		Placebo, 2 tablets twice daily (bid)
All Cause Mortality
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		2/29 (6.9%)
Infections and infestations
Pneumonia	0/26 (0%)		1/29 (3.4%)
LOWER RESPIRATORY TRACT INFECTION	0/26 (0%)		1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/26 (61.5%)		22/29 (75.9%)
Gastrointestinal disorders
Constipation	0/26 (0%)		2/29 (6.9%)
Diarrhoea	0/26 (0%)		2/29 (6.9%)
General disorders
Non-Cardiac Chest Pain	0/26 (0%)		2/29 (6.9%)
Pyrexia	0/26 (0%)		2/29 (6.9%)
Infections and infestations
Nasopharyngitis	3/26 (11.5%)		3/29 (10.3%)
Musculoskeletal and connective tissue disorders
Back Pain	1/26 (3.8%)		2/29 (6.9%)
Nervous system disorders
Headache	8/26 (30.8%)		7/29 (24.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/26 (7.7%)		1/29 (3.4%)
Oropharyngeal Pain	2/26 (7.7%)		1/29 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.