Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication CAYSTON ® is indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa . Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with FEV 1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14) ]. FDA label
Also known as Aztreonam for Inhalation Solution (AZLI), Aztreonam for Inhalation (AI), AZLI, inhaled antibiotic, Cayston®
Aztreonam · 9 trials · 6 indications
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.
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.
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.
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.
Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an analysis of covariance (ANCOVA) model-based method.
Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by mixed-effect model repeated measures (MMRM) analysis using the ITT population analysis set.
The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Evaluable Analysis Set.
The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Sensitivity Analysis Set.
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 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.
| Arm | Type | Description |
|---|---|---|
| AZLI | ACTIVE_COMPARATOR | Participants will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI for 28 days followed by TIS for 28 days. |
| Placebo | PLACEBO_COMPARATOR | Participants 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 AZLI | EXPERIMENTAL | Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. |
| AZLI-AZLI | EXPERIMENTAL | Participants 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-AZLI | PLACEBO_COMPARATOR | Participants 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. |
| AZLI 75 mg 3 times a day (TID) | EXPERIMENTAL | - |
| TIS 300 mg 2 times a day (BID) | ACTIVE_COMPARATOR | - |
| Aztreonam for Inhalation Solution (AZLI) | EXPERIMENTAL | Participants will receive one 28-day course of AZLI, then will be followed for a 24-week period (through Day 196). |
| AI 75 mg | EXPERIMENTAL | Aztreonam for Inhalation 75 mg twice daily |
| AI 225 mg | EXPERIMENTAL | Aztreonam for Inhalation 225 mg twice daily |
| Name | Type | Description |
|---|---|---|
| AZLI | DRUG | Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily combined with diluent administered using an eFlow nebulizer |
| Placebo to match AZLI | DRUG | Placebo to match AZLI 3 times daily combined with diluent administered using an eFlow nebulizer |
| Tobramycin inhalation solution | DRUG | Tobramycin inhalation solution (TIS) 300 mg 2 times daily using a PARI® LC Plus nebulizer and DeVilbiss Pulmo-Aide® air compressor |
| Placebo | DRUG | Placebo to match AZLI administered via nebulizer three times daily |
| Aztreonam for Inhalation Solution (AZLI) | DRUG | Aztreonam for inhalation solution (75 mg) was administered 3 times a day (TID) for 28 days for each treatment cycle via the PARI eFlow electronic nebulizer. |
| Tobramycin Inhalation Solution (TIS) | DRUG | Tobramycin inhalation solution (300 mg) was administered 2 times a day (BID) for 28 days for each treatment cycle via the PARI LC Plus nebulizer with compressor or via another nebulizer compatible with country-specified labeling. |
| Aztreonam for Inhalation (AI) | DRUG | Aztreonam for Inhalation |
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...
Top 6 of 7 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Vertex Pharmaceuticals Incorporated | VRTX | 8 | PHASE3 | Alyftrek, Trikafta, Ivacaftor, VX-581, VX-272 |
| BiomX Inc. | PHGE | 1 | PHASE2 | BX004 |
| 4D Molecular Therapeutics, Inc. | FDMT | 1 | PHASE2 | 4D-710 |
| Arcturus Therapeutics Holdings, Inc. | ARCT | 1 | PHASE2 | ARCT-032 |
| Krystal Biotech, Inc. | KRYS | 1 | PHASE1 | KB407 |
| Roivant Sciences Ltd. | ROIV | 1 | PHASE1 | SP-101 |
Aztreonam for inhalation is used to treat Pseudomonas aeruginosa lung infection in people with cystic fibrosis. It is a small molecule antibacterial given as an inhaled formulation. The clinical program covers cystic fibrosis patients with P. aeruginosa infection, including studies in adults and children as young as 3 months.
Aztreonam for inhalation is being developed by Gilead Sciences, Inc., which trades on Nasdaq under the ticker GILD. Gilead is the sponsor of the clinical program evaluating the inhaled formulation in cystic fibrosis patients with Pseudomonas aeruginosa infection.
Aztreonam for inhalation is in Phase 3 development. The Phase 3 study in the program is NCT00757237, which compared aztreonam for inhalation solution with tobramycin inhalation solution in cystic fibrosis patients with Pseudomonas aeruginosa. The drug is investigational and is not approved.
Three completed trials make up the program: NCT00757237, a Phase 3 comparison with tobramycin inhalation solution in 274 patients; NCT01375049, a Phase 2 Pseudomonas infection eradication study in 105 patients; and NCT01055847, a Phase 2 study in 105 cystic fibrosis patients with P. aeruginosa infection. All three are completed.
Yes. Aztreonam for inhalation is also known as Aztreonam for Inhalation Solution (AZLI) and Aztreonam for Inhalation (AI). These names refer to the same inhaled antibacterial formulation of aztreonam developed by Gilead Sciences for cystic fibrosis patients with Pseudomonas aeruginosa lung infection.
The aztreonam for inhalation program enrolled 484 patients across three completed trials. The Phase 3 study NCT00757237 enrolled 274 patients, while the two Phase 2 studies, NCT01375049 and NCT01055847, each enrolled 105 patients. The trials were randomized, double blind, and placebo controlled.