Cystic Fibrosis
Conditions
Keywords
cystic fibrosis
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).
Interventions
DRUGAZD9668
60 mg, oral tablet, twice daily for 28 days
DRUGAZD9668 Placebo equivalent
Match placebo to 60 mg, oral tablet, twice daily for 28 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
| 24-hour Sputum Weight | 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) | 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) | 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%) | Baseline and day 28 | FEF25-75% (L) as a measure of lung function. Change from Baseline to day 28. |
| Forced Vital Capacity (FVC) | 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) | 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) | 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 | 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. |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Denmark, Germany, Poland, Russia, Sweden, United Kingdom
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).
Participants by arm
| Arm | Count |
|---|---|
| AZD9668 AZD9668, 2 x 30 mg twice daily (bid) | 25 |
| Placebo Placebo, 2 tablets twice daily (bid) | 29 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Incorrect enrolment | 1 | 0 |
| Overall Study | Voluntary discontinuation | 1 | 0 |
Baseline characteristics
| Characteristic | AZD9668 | Placebo | Total |
|---|---|---|---|
| Age Continuous | 25 years | 25 years | 25 years |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 24 Participants | 29 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 26 | 22 / 29 |
| serious Total, serious adverse events | 0 / 26 | 2 / 29 |
Outcome results
Primary
24-hour Sputum Weight
Sputum weight (g) collected during 24 hour periods. Change from Baseline to day 28.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | 24-hour Sputum Weight | -2.29 grams | Standard Error 2.261 |
| Placebo | 24-hour Sputum Weight | -5.13 grams | Standard Error 2.178 |
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD9668 | Bronkotest Diary Card Signs and Symptoms | 0 Signs and Symptoms |
| Placebo | Bronkotest Diary Card Signs and Symptoms | 0 Signs and Symptoms |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Cystic Fibrosis Questionnaire (CFQ-R) - Quittner | -19.7 units on a scale | Standard Error 18.12 |
| Placebo | Cystic Fibrosis Questionnaire (CFQ-R) - Quittner | 4.7 units on a scale | Standard Error 14.93 |
Primary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Evening Peak Expiratory Flow (PEF) | 0.59 L/min | Standard Error 6.874 |
| Placebo | Evening Peak Expiratory Flow (PEF) | 6.32 L/min | Standard Error 6.194 |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | -0.07 L | Standard Error 0.09 |
| Placebo | Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | 0.08 L | Standard Error 0.082 |
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Forced Expiratory Volume in 1 Second (FEV1) | -0.02 L | Standard Error 0.048 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) | 0.01 L | Standard Error 0.043 |
Primary
Forced Vital Capacity (FVC)
Forced Vital Capacity (L) as a measure of lung function. Change from Baseline to day 28.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Forced Vital Capacity (FVC) | -0.06 L | Standard Error 0.066 |
| Placebo | Forced Vital Capacity (FVC) | 0.01 L | Standard Error 0.059 |
Primary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Morning Peak Expiratory Flow (PEF) | -1.17 L/min | Standard Error 8.055 |
| Placebo | Morning Peak Expiratory Flow (PEF) | 14.05 L/min | Standard Error 7.262 |
Primary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline | 1.07 ratio |
| Placebo | Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline | 1.10 ratio |
Primary
Slow Vital Capacity (SVC)
Slow Vital capacity (L) as a measure of lung function. Change from Baseline to day 28.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Slow Vital Capacity (SVC) | -0.03 L | Standard Error 0.106 |
| Placebo | Slow Vital Capacity (SVC) | -0.15 L | Standard Error 0.081 |
Primary
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)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9668 | Sputum Percentage Neutrophil Count | 3.21 percentage of neutrophils in WBCs | Standard Error 1.757 |
| Placebo | Sputum Percentage Neutrophil Count | 1.96 percentage of neutrophils in WBCs | Standard Error 1.566 |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | 0.95 ratio |
| Placebo | Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | 1.09 ratio |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | 0.71 ratio |
| Placebo | Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | 1.20 ratio |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | 0.86 ratio |
| Placebo | Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | 1.04 ratio |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | 1.02 ratio |
| Placebo | Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | 1.00 ratio |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | 0.73 ratio |
| Placebo | Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | 0.91 ratio |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | 0.91 ratio |
| Placebo | Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | 1.18 ratio |
Secondary
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
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
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | 0.91 ratio |
| Placebo | Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | 1.24 ratio |
Secondary
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 0.88 ratio |
| Placebo | Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 1.27 ratio |
Secondary
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD9668 | Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 0.68 ratio |
| Placebo | Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline | 0.97 ratio |