Clinical trial NCT01704495: A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Uncontrolled Asthma,
Exacerbation,
Safety
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-10-11
Enrollment: 1147
Sex: ALL
Minimum age (years): 18
Maximum age (years): 150
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Severe Asthma Exacerbations During 6 Months
timeFrame: From start of treatment up to 6 months
Secondary outcomes:
measure: Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months
timeFrame: From start of treatment up to 6 months
measure: Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions
timeFrame: From start of treatment up to 6 months
measure: Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms
timeFrame: From start of treatment up to 6 months
measure: Change From Baseline to 2 Weeks Measurement of Pre-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 2 weeks after Day 0
measure: Change From Baseline to 1 Month Measurement of Pre-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 1 month after Day 0
measure: Change From Baseline to 2 Months Measurement of Pre-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 2 months after Day 0
measure: Change From Baseline to 3 Months Measurement of Pre-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 3 months after Day 0
measure: Change From Baseline to 4 Months Measurement of Pre-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 4 months after Day 0
measure: Change From Baseline to 6 Months Measurement of Pre-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 6 months after Day 0
measure: Change From Baseline to 2 Weeks Measurement of Post-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 2 weeks after Day 0
measure: Change From Baseline to 1 Month Measurement of Post-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 1 month after Day 0
measure: Change From Baseline to 2 Months Measurement of Post-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 2 months after Day 0
measure: Change From Baseline to 3 Months Measurement of Post-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 3 months after Day 0
measure: Change From Baseline to 4 Months Measurement of Post-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 4 months after Day 0
measure: Change From Baseline to 6 Months Measurement of Post-bronchodilator FEV1
timeFrame: Baseline (Day 0) and 6 months after Day 0
measure: Change From Baseline to Overall Mean of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version) Total Score
timeFrame: Baseline (Day 0), Treatment Period (1,2,3,4, and 6 months)
measure: Number of Patients Presenting Improvement From Baseline to End of Treatment Period in ACQ-5 (Asthma Control Questionnaire, 5-item Version)
timeFrame: Baseline (Day 0) and 6 months after Day 0
measure: Change From Baseline to Overall Mean of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score
timeFrame: Baseline (Day 0), Treatment Period (1,3, and 6 months)
measure: Number of Patients Presenting Improvement From Baseline to End of Treatment Period in AQLQ(S) (Asthma Quality of Life Questionnaire Standardised Version) Overall Score
timeFrame: Baseline (Day 0) and 6 months after Day 0
measure: Change From Baseline to Treatment Period (Day 1 to Day 28) for Astma Symptom Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
measure: Change From Baseline to Treatment Period (Day 29 to Day 56) for Astma Symptom Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
measure: Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Symptom Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
measure: Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Symptom Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)
measure: Change From Baseline to Treatment Period (Day 1 to Day 28) for Asthma Control Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
measure: Change From Baseline to Treatment Period (Day 29 to Day 56) for Asthma Control Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
measure: Change From Baseline to Treatment Period (Day 57 to Day 84) for Asthma Control Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
measure: Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Asthma Control Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months
measure: Change From Baseline to Treatment Period (Day 1 to Day 28) for Use of Rescue Medication Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
measure: Change From Baseline to Treatment Period (Day 29 to Day 56) for Use of Rescue Medication Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 29 to 56)
measure: Change From Baseline to Treatment Period (Day 57 to Day 84) for Use of Rescue Medication Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 57 to 84)
measure: Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Use of Rescue Medication Free Days
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 85 to 6 months)
measure: Change From Baseline to Treatment Period (Day 1 to Day 28) for Night Time Awakenings Due to Asthma Symptoms
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Days 1 to 28)
measure: Change From Baseline to Treatment Period (Day 29 to Day 56) for Night Time Awakenings Due to Asthma Symptoms
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Day 29 to Day 56)
measure: Change From Baseline to Treatment Period (Day 57 to Day 84) for Night Time Awakenings Due to Asthma Symptoms
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Day 57 to Day 84)
measure: Change From Baseline to Treatment Period (Day 85 to End of Treatment [6 Months]) for Night Time Awakenings Due to Asthma Symptoms
timeFrame: Baseline (last 14 days before randomization) and Treatment Period (Day 85 to 6 months)
measure: Number of Participants With Well Controlled Asthma Weeks at Baseline
timeFrame: Last 2 weeks before randomization
measure: Number of Well Controlled Asthma Weeks During Treatment
timeFrame: Day 1to end of the 6 months treatment period
measure: Number of Participants With Uncontrolled Persistent Asthma Weeks at Baseline
timeFrame: Last 2 weeks before randomization
measure: Number of Uncontrolled Persistent Asthma Weeks During Treatment
timeFrame: Day 1 to end of the 6 months treatment period
measure: Mean Plasma Concentration of AZD5069 at Day 7
timeFrame: Day 7
measure: Mean Plasma Concentration of AZD5069 at 1 Month
timeFrame: at 1 month
Other outcomes:
Locations:
city: Gotse Delchev
country: Bulgaria
facility: Research Site
city: Kozloduy
country: Bulgaria
facility: Research Site
city: Petrich
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Razgrad
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Vidin
country: Bulgaria
facility: Research Site
city: Mount Pearl
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Saint-Romuald
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Jindrichuv Hradec
country: Czech Republic
facility: Research Site
city: Karlovy Vary
country: Czech Republic
facility: Research Site
city: Kutna Hora
country: Czech Republic
facility: Research Site
city: Melnik
country: Czech Republic
facility: Research Site
city: Praha 5
country: Czech Republic
facility: Research Site
city: Praha 6
country: Czech Republic
facility: Research Site
city: Strakonice
country: Czech Republic
facility: Research Site
city: Tabor
country: Czech Republic
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Großhansdorf
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Aszód
country: Hungary
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Cegléd
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Komárom
country: Hungary
facility: Research Site
city: Makó
country: Hungary
facility: Research Site
city: Monor
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Szombathely
country: Hungary
facility: Research Site
city: Százhalombatta
country: Hungary
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Giżycko
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Proszowice
country: Poland
facility: Research Site
city: Skierniewice
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Żnin
country: Poland
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Constanta
country: Romania
facility: Research Site
city: Deva
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Vladikavkaz
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Bardejov
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Komarno
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Spisska Nova Ves
country: Slovakia
facility: Research Site
city: Surany
country: Slovakia
facility: Research Site
city: Topolcany
country: Slovakia
facility: Research Site
city: Trencin
country: Slovakia
facility: Research Site
city: Zvolen
country: Slovakia
facility: Research Site
city: Amanzimtoti
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Umkomaas
country: South Africa
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Zaporizhzhzya
country: Ukraine
facility: Research Site
city: Zaporozye
country: Ukraine
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AZ Mondal R&D, Sweden
name: Bengt Larsson, MEDICAL SCIENCE DIRECTOR
role: STUDY_DIRECTOR
References:
citation: O'Byrne PM, Metev H, Puu M, Richter K, Keen C, Uddin M, Larsson B, Cullberg M, Nair P. Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2016 Oct;4(10):797-806. doi: 10.1016/S2213-2600(16)30227-2. Epub 2016 Aug 27.