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AZLI

Phase 3

Bronchiectasis | Small molecule | Respiratory |Gilead Sciences, Inc.|Last Updated: May 9, 2016

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials3
Total Enrollment629

FDA Designations

No designations recorded

Clinical trial landscape

AZLI · 6 trials · 4 indications

Phase 3 5Phase 2 1
NCT01641822Phase 3 Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy Regimen for the Treatment of Chronic Pseudomonas Aeruginosa Infection in Patients With CFCystic Fibrosis
COMPLETED107 Analytics
NCT01404234Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower AirwaysCystic Fibrosis
COMPLETED61 Analytics
NCT01313624Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis BronchiectasisBronchiectasis
COMPLETED266 Analytics
NCT01314716Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis BronchiectasisBronchiectasis
COMPLETED274 Analytics
NCT01059565Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species InfectionCystic Fibrosis
COMPLETED102 Analytics
PHASE3COMPLETED
Phase 3 Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy Regimen for the Treatment of Chronic Pseudomonas Aeruginosa Infection in Patients With CF
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower Airways
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
BronchiectasisUnlock trial analytics
PHASE3COMPLETED
Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
BronchiectasisUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection
Cystic FibrosisUnlock trial analytics

Study Endpoints

Primary Endpoints

Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)

PDEs were characterized by a change or worsening from baseline of 1 or more documented signs or symptoms (decreased exercise tolerance, increased cough, increased sputum or chest congestion, decreased appetite, or other signs or symptoms) associated with the use of non-study IV or inhaled antibiotics and be verified by a blinded independent adjudication committee.

Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons
Baseline to Day 168

Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method.

Change in QOL-B Respiratory Symptoms Score at Day 28
Baseline to Day 28

The mean (SD) change in the Respiratory Symptoms score on the Quality of Life Questionnaire-Bronchiectasis (QOL-B) was measured from baseline to the end of Course 1 (Day 28). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24
Baseline to Week 24

The relative change (AUCave) in FEV1 % predicted from baseline to Week 24 was analyzed. FEV1 % predicted is defined as FEV1 % of the patient divided by the average FEV1 % in the population for any person of similar age, sex and body composition. AUCave is the calculated area under the curve corrected for baseline and adjusted by the number of days on study through Week 24.

Reliability of the Respiratory Domain of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)
Day -14 to Day 0

Test-retest reliability is a measure of the stability or reproducibility of a measure over a period of time during which status on the underlying construct has not changed, and is measured by the intraclass correlation of scores obtained at 2 time points within that period. Test-retest reliability of respiratory symptoms was calculated for response at Day -14 and Day 0. Reliability of the participants' QOL-B responses was assessed from an Intraclass Correlation Coefficient (ICC). A score of ≥ 0.70 would indicate strong reliability. The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Convergent Validity of the Respiratory Domain of the QOL-B
Day -14

Convergent validity was assessed at Day -14 by examining the correlations between relevant QOL-B domains and other indicators of health status: a bronchiectasis severity score based on high-resolution computerised tomography (HRCT) scan results, forced expiratory volume in 1 second (FEV1) percent predicted, 6-minute walk test (6MWT) results, and St. George's Respiratory Questionnaire (SGRQ) symptoms scores. Correlations with absolute values of 0.30 to 0.50 indicated moderate evidence of convergent validity.

Secondary Endpoints

Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)
Comparative Phase: Baseline and Weeks 4, 12 and 20
Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
Time to First Protocol-defined Pulmonary Exacerbation
Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days)
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
AZLIACTIVE_COMPARATORParticipants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI for 28 days followed by TIS for 28 days.
PlaceboPLACEBO_COMPARATORParticipants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS for 28 days.
Open-label AZLIEXPERIMENTALParticipants received three 28-day courses of AZLI, each followed by 28 days off-treatment.
AZLI-AZLIEXPERIMENTALParticipants were randomized to receive blinded AZLI for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI for 28 days plus 56 days of treatment-free follow-up.
Placebo-AZLIPLACEBO_COMPARATORParticipants were randomized to receive blinded placebo to match AZLI for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI for 28 days plus 56 days of treatment-free follow-up.

Interventions

NameTypeDescription
AZLIDRUGAztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer
Placebo to match AZLIDRUGPlacebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer
Tobramycin inhalation solutionDRUGTobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor
PlaceboDRUGPlacebo to match AZLI administered via nebulizer three times daily
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Eligibility Criteria

Age Range6 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites71

Inclusion Criteria: * Confirmed diagnosis of CF * Presence of PA in 2 lower respiratory tract cultures in the 12 months prior to screening * Forced expiratory volume (FEV)1 ≥ 25 and ≤ 75% predicted * History of 1 hospitalization or 1 course of IV antibiotics for an acute respiratory exacerbation in...

Countries:United StatesFranceGermanyItalyPolandSpainAustraliaCanadaBelgiumNetherlandsUnited Kingdom
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Competitive Landscape -Bronchiectasis 8 trials

Frequently asked questions about AZLI

What is AZLI used for?

AZLI is an investigational small molecule being developed for cystic fibrosis and bronchiectasis. It is a formulation of aztreonam for inhalation solution, studied in patients with cystic fibrosis who have chronic Pseudomonas aeruginosa or Burkholderia species infections. It is not FDA approved and remains in clinical development.

Who makes AZLI?

AZLI is being developed by Gilead Sciences, Inc., traded on NASDAQ under the ticker GILD. The company is conducting clinical trials of AZLI in respiratory conditions including cystic fibrosis and bronchiectasis.

What phase is AZLI in?

AZLI is in Phase 3 clinical development. It is an investigational drug and has not received FDA approval. Multiple Phase 3 trials have been completed, but the drug is not yet approved for any indication.

What clinical trials is AZLI in?

AZLI has been studied in several completed trials, including NCT01059565 in cystic fibrosis patients with chronic Burkholderia infection, NCT01404234 in children with cystic fibrosis and Pseudomonas aeruginosa, and NCT01641822 in a continuous alternating therapy regimen for chronic Pseudomonas aeruginosa infection.

Is AZLI the same as aztreonam for inhalation solution?

Yes, AZLI is aztreonam for inhalation solution. Clinical trial titles refer to it as Aztreonam for Inhalation Solution (AZLI), and it is being studied as an inhaled antibiotic therapy for respiratory infections in cystic fibrosis patients.