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

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

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).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: AZD9668; Drug: AZD9668 Placebo equivalent

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Kobenhavn, Denmark
    • Research Site
• Germany
  • Hamburg, Germany
    • Research Site
  • Kiel, Germany
    • Research Site
  • Leipzig, Germany
    • Research Site
  • Munchen, Germany
    • Research Site
• Poland
  • Rabka-zdroj, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
• Russian Federation
  • Moscow, Russian Federation
    • Research Site
• Sweden
  • Goteborg, Sweden
    • Research Site
  • Lund, Sweden
    • Research Site
  • Stockholm, Sweden
    • Research Site
  • Uppsala, Sweden
    • Research Site
• United Kingdom
  • Liverpool, United Kingdom
    • Research Site
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits	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	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits	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	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits	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	Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
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	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
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	End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline	Ratio of day 28 to baseline	Baseline and day 28
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline	Ratio of day 28 to baseline	Baseline and day 28

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: September 22, 2008
• First Submitted That Met QC Criteria: September 22, 2008
• First Posted (Estimate): September 23, 2008

Study Record Updates

• Last Update Posted (Estimate): August 20, 2012
• Last Update Submitted That Met QC Criteria: August 14, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: cystic fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: D0520C00009