A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma.

Asthma Clinical Trial

— NIMBUS  

Official title:

A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study With an Optional Safety Extension Treatment Period up to 6 Months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients With Uncontrolled Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01704495
• Other study ID #: D3551C00001
• Secondary ID: 2012-001869-33
• Status: Completed
• Phase: Phase 2
• First received: October 9, 2012
• Last updated: February 1, 2016
• Start date: November 2012
• Est. completion date: August 2014

Study information

• Verified date: February 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyBulgaria: Bulgarian Drug AgencySlovakia: State Institute for Drug ControlHungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsGermany: Federal Institute for Drugs and Medical DevicesRomania: National Medicines AgencyRussia: Ministry of Health of the Russian FederationMexico: Federal Commission for Protection Against Health RisksUkraine: State Pharmacological Center - Ministry of HealthCanada: Health CanadaSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial Summary

The purpose is to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

Description:

A 6-month, Randomised, Double-blind, Placebo-controlled, Multi-centre, Parallel-group, Phase II Study with an Optional Safety Extension Treatment Period up to 6 months, to Evaluate the Efficacy, Safety, and Tolerability of 3 Different Doses of AZD5069 Twice Daily as Add-on Treatment to Medium to High Dose Inhaled Corticosteroids (ICS) and Long-acting β2 Agonists (LABA), in Patients with Uncontrolled Persistent Asthma

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1147
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 150 Years

Eligibility

Inclusion Criteria:

• Men and women aged 18 years and above. Females of childbearing potential must use a highly effective contraceptive method plus a condom by their male partner.

• Diagnosis of asthma for at least 12 months (GINA 2011)

• Uncontrolled persistent asthma, despite treatment with medium to high dose ICS and LABA, and with a history of exacerbations during the last year

• Morning prebronchodilator FEV1 of =30% and =85% predicted normal at enrolment

• Daily use of medium or high dose ICS (=fluticasone 500 µg or the equivalent daily)

Exclusion Criteria:

• Any clinically significant disease or disorder (including any chronic lower respiratory disease other than asthma) that may put the patient at risk or influence study results

• Patients with recurrent, latent, or chronic infections

• Active tuberculosis or latent tuberculosis without completion of an appropriate course of treatment or prophylactic treatment

• Significant lower respiratory tract infection not resolved within 30 days prior to enrolment

• Current smoker or smoking history of more than 20 pack years

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• AZD5069
AZD5069 oral capsules self-administered twice daily.
• Placebo
Placebo oral capsules self-administered twice daily.

Locations

Country	Name	City	State
Bulgaria	Research Site	Gotse Delchev
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Petrich
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Razgrad
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Vidin
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Mount Pearl	Newfoundland and Labrador
Canada	Research Site	Quebec
Canada	Research Site	Saint-Romuald	Quebec
Canada	Research Site	Toronto	Ontario
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Jindrichuv Hradec
Czech Republic	Research Site	Karlovy Vary
Czech Republic	Research Site	Kutna Hora
Czech Republic	Research Site	Melnik
Czech Republic	Research Site	Praha 5
Czech Republic	Research Site	Praha 6
Czech Republic	Research Site	Strakonice
Czech Republic	Research Site	Tabor
Germany	Research Site	Berlin
Germany	Research Site	Großhansdorf
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	München
Hungary	Research Site	Aszód
Hungary	Research Site	Baja
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Cegléd
Hungary	Research Site	Gyula
Hungary	Research Site	Komárom
Hungary	Research Site	Makó
Hungary	Research Site	Monor
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Százhalombatta
Hungary	Research Site	Szeged
Hungary	Research Site	Szombathely
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Gizycko
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Proszowice
Poland	Research Site	Skierniewice
Poland	Research Site	Tarnów
Poland	Research Site	Wroclaw
Poland	Research Site	Znin
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Constanta
Romania	Research Site	Deva
Romania	Research Site	Iasi
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Yaroslavl
Slovakia	Research Site	Bardejov
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Komarno
Slovakia	Research Site	Kosice
Slovakia	Research Site	Levice
Slovakia	Research Site	Poprad
Slovakia	Research Site	Spisska Nova Ves
Slovakia	Research Site	Surany
Slovakia	Research Site	Topolcany
Slovakia	Research Site	Trencin
Slovakia	Research Site	Zvolen
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Pretoria
South Africa	Research Site	Umkomaas
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhzya
Ukraine	Research Site	Zaporozye
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Bulgaria,  Canada,  Czech Republic,  Germany,  Hungary,  Mexico,  Poland,  Romania,  Russian Federation,  Slovakia,  South Africa,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Severe Asthma Exacerbations During 6 Months		From start of treatment up to 6 months	No
Secondary	Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months		From start of treatment up to 6 months	No
Secondary	Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions		From start of treatment up to 6 months	No
Secondary	Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms		From start of treatment up to 6 months	No
Secondary	Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis	Baseline (Day 0) and 2 weeks after Day 0	No
Secondary	Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at one month are included in the analysis	Baseline (Day 0) and 1 month after Day 0	No
Secondary	Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two months are included in the analysis	Baseline (Day 0) and 2 months after Day 0	No
Secondary	Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at three months are included in the analysis	Baseline (Day 0) and 3 months after Day 0	No
Secondary	Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at four months are included in the analysis	Baseline (Day 0) and 4 months after Day 0	No
Secondary	Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at six months are included in the analysis	Baseline (Day 0) and 6 months after Day 0	No
Secondary	Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two weeks are included in the analysis	Baseline (Day 0) and 2 weeks after Day 0	No
Secondary	Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at one month are included in the analysis	Baseline (Day 0) and 1 month after Day 0	No
Secondary	Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at two months are included in the analysis	Baseline (Day 0) and 2 months after Day 0	No
Secondary	Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at three months are included in the analysis	Baseline (Day 0) and 3 months after Day 0	No
Secondary	Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at four months are included in the analysis	Baseline (Day 0) and 4 months after Day 0	No
Secondary	Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1	Only patients with both a non-missing value at baseline and visit at six months are included in the analysis	Baseline (Day 0) and 6 months after Day 0	No
Secondary	Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score	The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).	Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months)	No
Secondary	Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version)	The ACQ-5 is a validated questionnaire consisting of 5 items for the assessment of asthma symptom which are night symptom, morning symptom, limitation for the activities, shortness of breath, and wheeze. Each item is graded on a scale of 0-6 and the questions are equally weighted. The ACQ-5 score is the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).	Baseline (Day 0) and 6 months after Day 0	No
Secondary	Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score	The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score.	Baseline (Day 0), Treatment Period (1,3, and 6 months)	No
Secondary	Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score	The AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments in asthma. Patients are asked to score each item on a 7-point scale based on the experience of last 2 weeks. The overall AQLQ score is the mean response to all 32 questions. Therefore, the possible highest score (better) would be 7 and the lowest (worse) would be 1. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score.	Baseline (Day 0) and 6 months after Day 0	No
Secondary	Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)	No
Secondary	Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)	No
Secondary	Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)	No
Secondary	Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days		Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)	No
Secondary	Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)	No
Secondary	Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)	No
Secondary	Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)	No
Secondary	Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days		Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months	No
Secondary	Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)	No
Secondary	Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)	No
Secondary	Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)	No
Secondary	Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days		Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months)	No
Secondary	Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)	No
Secondary	Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Day 29 to Day 56)	No
Secondary	Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Day 57 to Day 84)	No
Secondary	Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms		Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)	No
Secondary	Number of Participants With Well Controlled Asthma Weeks at Baseline		Last 2 weeks before randomization	No
Secondary	Number of Well Controlled Asthma Weeks During Treatment		Day 1to end of the 6 months treatment period	No
Secondary	Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline		Last 2 weeks before randomization	No
Secondary	Number of Uncontrolled Persistent Asthma Weeks During Treatment		Day 1 to end of the 6 months treatment period	No
Secondary	Mean Plasma Concentration of AZD5069 at Day 7		Day 7	No
Secondary	Mean Plasma Concentration of AZD5069 at 1 Month		at 1 month	No