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

NCT00757848 | Completed Phase 2 Results

• 1 other identifier: D0520C00009
• Study Type: interventional
• Target: 56
• Locations: 6 countries
• Sites: 14

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).

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis

Outcome Measures

Primary Outcomes (11)

• 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

  Baseline and Values from day 21 to 28

• Sputum Percentage Neutrophil Count

  Percentage of neutrophils in white blood cell count.Change from Baseline (mean of 2 baseline visits) to the end of the treatment period (mean of 2 visits at the end of the treatment)

  Baseline and Values from day 21 to 28

• 24-hour Sputum Weight

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

  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

• 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 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.

  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

• 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

  Last 7 days on treatment

• Evening Peak Expiratory Flow (PEF)

  Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from baseline value to mean of the last 7 days on treatment

  The last 7 days on treatment

• Bronkotest Diary Card Signs and Symptoms

  The Bronkotest diary card includes 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). ANOVA models were fitted to compare the change from baseline between AZD9668 and placebo for each question separately, with a p-value of 0.1 considered statistically significant. The number of number of these 8 measures with significant differences is reported.

  The last 7 days on treatment

• Cystic Fibrosis Questionnaire (CFQ-R) - Quittner

  Cystic Fibrosis Questionnaire Overall Score as a measure of quality of life and disease symptoms. Scores range from 0 to 100, with higher scores indicating better health. The overall score is the sum of 12 subscores. Change from baseline to day 28.

  Baseline and day 28

Secondary Outcomes (9)

• 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 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 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 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 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

Study Arms (2)

AZD9668

EXPERIMENTAL

Drug: AZD9668

Placebo

PLACEBO COMPARATOR

Drug: AZD9668 Placebo equivalent

Interventions

AZD9668 DRUG

60 mg, oral tablet, twice daily for 28 days

AZD9668

AZD9668 Placebo equivalent DRUG

Match placebo to 60 mg, oral tablet, twice daily for 28 days

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (14)

Research Site

Copenhagen, Denmark

Location

Research Site

Hamburg, Germany

Location

Research Site

Kiel, Germany

Location

Research Site

Leipzig, Germany

Location

Research Site

München, Germany

Location

Research Site

Rabka-Zdrój, Poland

Location

Research Site

Warsaw, Poland

Location

Research Site

Moscow, Russia

Location

Research Site

Gothenburg, Sweden

Location

Research Site

Lund, Sweden

Location

Research Site

Stockholm, Sweden

Location

Research Site

Uppsala, Sweden

Location

Research Site

Belfast, Northern Ireland, United Kingdom

Location

Research Site

Liverpool, United Kingdom

Location

Related Publications (1)

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

  PMID: 22267768 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

N-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Study Officials

• Prof. Elborn

  Belfast hospital

  PRINCIPAL INVESTIGATOR

• Joanna Marks-Konczalik

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2008
• First Posted: September 23, 2008
• Study Start: October 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: August 20, 2012
• Results First Posted: July 25, 2012

Record last verified: 2012-08

Locations

SE (4); DK (1); GB (2); DE (4); PL (2); RU (1)