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AZD5069

Phase 2

Asthma | Small molecule | Respiratory |AstraZeneca PLC|Last Updated: Mar 1, 2016

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials2
Total Enrollment1,160

FDA Designations

No designations recorded

Clinical trial landscape

AZD5069 · 11 trials · 17 indications

Phase 2 3Phase 1 8
NCT01704495A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma.Asthma
COMPLETED1,147 Analytics
NCT01255592Evaluation of the Effect of AZD5069 in Patients With BronchiectasisBronchiectasis
COMPLETED83 Analytics
NCT01233232A 4 Week Study to Investigate the Safety and Tolerability of AZD5069 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD)
COMPLETED109 Analytics
PHASE2COMPLETED
A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of AZD5069 in Patients With Uncontrolled Persistent Asthma.
AsthmaUnlock trial analytics
PHASE2COMPLETED
Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis
BronchiectasisUnlock trial analytics
PHASE2COMPLETED
A 4 Week Study to Investigate the Safety and Tolerability of AZD5069 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD)Unlock trial analytics

Study Endpoints

Primary Endpoints

Rate of Severe Asthma Exacerbations During 6 Months
From start of treatment up to 6 months
Ratio of Absolute Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.

Patients Who Experienced at Least One Adverse Events(s)
From start of treatment (Day 0) up to 28 days (End of Treatment)

Adverse event (AE) data, both serious and non-serious. An AE is the development of an undesirable medical condition (eg, nausea, chest pain, tachycardia, laboratory findings) or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Number of Participants With Abnormal Physical Examination Findings
Last Observation on Treatment (up to Day 28)

Physical examination includes assessment of general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, musculo-skeletal (including spine and extremities), cardiovascular, lungs and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator.

Number of Participants With Abnormal Electrocardiogram (ECG)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

ECGs were recorded in the supine position after the patient has rested for 10 minutes. Heart rate, QRS duration, PR, RR and QT intervals were recorded. Overall evaluation of the ECG is classified as normal, abnormal or borderline. Only participants with ECG at baseline classified as normal are reported (ie, only changes from normal to abnormal).

Change From Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in circulating leucocyte counts (including neutrophils) is calculated as the End of Treatment value minus the Baseline value.

Change From Baseline to End of Treatment for Body Temperature
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in body temperature (oral) is calculated as the End of Treatment value minus the Baseline value.

Change From Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in systolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.

Change From Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in diastolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.

Change From Baseline to End of Treatment for Pulse Rate (Vital Signs)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in pulse rate (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.

Change From Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in FEV1 Pre-bronchodilator is calculated as the End of Treatment value minus the Baseline value.

Change From Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in FEV1 Post-bronchodilator is calculated as the End of Treatment value minus the Baseline value.

Number of Participants Who Developed High Transaminase Values (Clinical Chemistry)
Up to Follow-up Visit (3 to 18 days after End of Treatment [Day 28])

High Transaminase Values are defined as a measurment of ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than or equal to 3 times the upper limit of normal (ALT ULN = 36 IU/L, AST ULN = 33 IU/L).

Change From Baseline to End of Treatment for Total Protein (Urinalysis)
Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)

The change in total protein in urine is calculated as the End of Treatment value minus the Baseline value.

Summary for Change From Baseline of Mean Global Semi-quantitative Score Values for Neutrophils in Bronchial Biopsies
Baseline and Week 4

Change from baseline reflects the Week 4 value minus the baseline value. Baseline value is Day-14 measurement. For semi-quantitative scores, 1= few number of Neutrophils, 2= moderate number of Neutrophils, 3= abundant of Neutrophils. For this end point the reduction in mean of semi-quantitative (arbitrary) scores indicates better result, i.e. lower numbers of Neutrophils. The scores given for the biopsies taken at screening and end of treatment is the mean global semi-quantitative scores for the three compartments intraepithelial, subepithelial and submucosal.

Summary for Change From Baseline Neutrophils in Sputum
Baseline, Day 8, Day 22 and Day29

Change from Baseline reflects the Day 8, Day22 and Day29 minus the baseline value.

Summary for Change From Baseline Neutrophil Cell Counts in Blood
Baseline, Day 2, Day 8, Day 15, Day 22, Day29 and Day 34

Change from Baseline reflects the Day 2, Day 8, Day 15, Day 22, Day29 and Day 34 minus the baseline value

Pharmacokinetics of AZD5069 (15 mg) and a metabolite (AZ13587715) measured by AUC, AUC(0-t), Cmax, λz, t½λz, tmax, CL/F (AZD5069 only), Vz/F (alone and in combination with Ketoconazole)
Day 1, Day 2 at 24 hours post dose and Day 3 at 48 hours post dose in period 1 and Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.

(AUC(0-t)) area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, (Cmax) observed maximum plasma concentration, (λz) terminal rate constant, (t½λz) terminal half-life, (tmax) time to reach maximum plasma concentration (tmax), (CL/F) apparent oral clearance (AZD5069 only), (Vz/F) apparent volume of distribution.

Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069)
Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.
Change in status of Neutrophil function (phagocytosis and oxidative burst) in subjects on AZD5069 and placebo
Day -1, Day 1, Day 2, Day 3, Day 4 and 7 days after end of treatment.
Circulating neutrophils during exercise challenge measured by average neutrophil values over time
Pre-dose, 10 min, 2h, 4 hours post exercise test
Circulating neutrophils following subcutaneous injection of granulocyte-colony stimulating factor (G-CSF)
Pre-dose, 2h, 6h, 12h, 24h, 36 hours post subcutaneous G-CSF
To investigate the absorption, distribution, metabolism and excretion of AZD5069 in human subjects by measuring the amount of [14C] radioactivity in plasma and whole blood
From pre-dose until 168 hours post last dose

To investigate the absorption, distribution, metabolism and excretion of AZD5069 in human subjects by measuring the amount of \[14C\] radioactivity in plasma and whole blood and the resulting area under the concentration-time curve from zero extrapolated to infinity (AUC), to the last measurable concentration (AUC(0 t)).

To investigate the absorption, distribution, metabolism and excretion of AZD5069 in human subjects by measuring Plasma [14C] AZD5069:AZD5069 (cold) ratios for concentrations and selected pharmacokinetic parameters (AUCs and Cmax).
From pre-dose until 168hours post last dose
To investigate the excretion of AZD5069 in human subjects by measuring the amount and percentage of radioactive dose recovered in urine, faeces, and renal clearance.
From pre-dose until 168hours post last dose
Adverse events, electrocardiograms (ECGs), laboratory variables, blood pressure, pulse rate, body temperature, QT interval and continuous cardiac monitoring using telemetry
From screening period to follow-up visit 42 days (Maximum)
Pharmacokinetic blood to measure Maximum plasma concentration (Cmax); time to Cmax (tmax); and the area under the plasma concentration-time curve from zero to infinity (AUC).
0 - 72 hours postdose
Safety and tolerability of AZD5069 assessing vitals signs (blood pressure, pulse rate,body temperature), ECG,laboratory variables (including high sensitivity C-reactive protein, circulating neutrophils), continuous cardiac monitoring using telemetry.
Baselines assessments at Visit 1 (enrolment). Assessments pre-dose at Visit 2 and at protocol defined time-points post-dose. Follow up assessments at Visit 3.

Secondary Endpoints

Rate of Asthma-specific Hospital Admission/Intensive Care Unit Admissions During 6 Months
From start of treatment up to 6 months
Total Number of Days of Asthma-specific Hospital Admission/Intensive Care Unit Admissions
From start of treatment up to 6 months
Total Number of Days on Oral Cortecosteroids, Due to a Worsening of Asthma Symptoms
From start of treatment up to 6 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
AZD5069 5 mgEXPERIMENTALAZD5069 oral capsules self-administered twice daily
AZD5069 15 mgEXPERIMENTALAZD5069 oral capsules self-administered twice daily
AZD5069 45 mgEXPERIMENTALAZD5069 oral capsules self-administered twice daily
PlaceboPLACEBO_COMPARATORPlacebo oral capsules self-administered twice daily
1EXPERIMENTALTreatment arm AZD5069
2PLACEBO_COMPARATORPlacebo dose.
3EXPERIMENTALTreatment arm AZD5069 80mg
First AZD5069, then Ketoconazole + AZD5069EXPERIMENTALAZD5069 in first period (on 1 day) and in second period (after wash out) ketoconazole alone (on 2 days) then ketoconazole + AZD5069 (on 1 day), then again ketoconazole alone (on 2 days)
ActiveEXPERIMENTALAZD5069 oral solution

Interventions

NameTypeDescription
AZD5069DRUGAZD5069 oral capsules self-administered twice daily.
PlaceboDRUGPlacebo oral capsules self-administered twice daily.
AZD5069 50mgDRUGOral dose bid
AZD5069 80mgDRUGOral dose bid
KetoconazoleDRUGKetoconazole 400 mg (2x200 mg tablets)
100 mg (50 mg x 2) AZD5069DRUGTwice daily for 7 days
100 mg PlaceboDRUGTwice daily for 7 days
[14C] AZD5069DRUGSingle 120 mg oral dose administered on Day 1
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Eligibility Criteria

Age Range18 Years to 150 Years
SexALL
Healthy VolunteersNo
Study Sites96

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 medi...

Countries:BulgariaCanadaCzechiaGermanyHungaryMexicoPolandRomaniaRussiaSlovakiaSouth AfricaUkraineUnited Kingdom
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Frequently asked questions about AZD5069

What is AZD5069 used for?

AZD5069 is an investigational small molecule being studied for respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. It has been evaluated in clinical trials for uncontrolled persistent asthma and bronchiectasis. The drug is not approved and remains in clinical development.

What does AZD5069 target?

AZD5069 targets the chemokine receptor 2 (CXCR2), a receptor involved in neutrophil recruitment and inflammation. By antagonizing CXCR2, the drug aims to reduce neutrophil-driven inflammation in respiratory diseases. This mechanism is relevant to conditions like asthma and bronchiectasis where neutrophilic inflammation plays a role.

Who makes AZD5069?

AZD5069 is developed by AstraZeneca PLC, a multinational pharmaceutical company listed on the stock exchange under the ticker AZN. AstraZeneca has sponsored clinical trials of AZD5069 in respiratory indications, including asthma and bronchiectasis.

What phase is AZD5069 in?

AZD5069 has completed Phase 2 clinical trials. It has been studied in a Phase 2 trial for uncontrolled persistent asthma and a Phase 2 trial for bronchiectasis. The drug is investigational and has not received FDA approval. No active trials are currently listed for AZD5069.

What clinical trials is AZD5069 in?

AZD5069 has completed four clinical trials. These include NCT00953888, a Phase 1 healthy volunteer study; NCT01255592, a Phase 2 bronchiectasis trial; NCT01704495, a Phase 2 asthma trial; and NCT01890148, a Phase 1 asthma study. All trials are completed, with no active trials ongoing.

Is AZD5069 the same as other names?

AZD5069 is the primary name for this investigational drug. No alternative names have been reported. It is sometimes referred to as AZD 5069 in clinical trial documents, but this is a formatting variation rather than a distinct name.