CLINICAL TRIALS PROFILE FOR ZERBAXA

All Clinical Trials for ZERBAXA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02421120 ↗	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients	Completed	Cubist Pharmaceuticals LLC	Phase 4	2015-09-01	There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Ceftolozane/Tazobactam is a newly approved broad spectrum intravenous antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, the most common pathogen implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of ceftolozane/tazobactam in 20 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of ceftolozane and tazobactam. Safety and tolerability will be assessed throughout the 3 day study.
NCT02421120 ↗	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients	Completed	Indiana University Health	Phase 4	2015-09-01	There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Ceftolozane/Tazobactam is a newly approved broad spectrum intravenous antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, the most common pathogen implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of ceftolozane/tazobactam in 20 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of ceftolozane and tazobactam. Safety and tolerability will be assessed throughout the 3 day study.
NCT02421120 ↗	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients	Completed	Riley Hospital for Chilren at Indiana University Health	Phase 4	2015-09-01	There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Ceftolozane/Tazobactam is a newly approved broad spectrum intravenous antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, the most common pathogen implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of ceftolozane/tazobactam in 20 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of ceftolozane and tazobactam. Safety and tolerability will be assessed throughout the 3 day study.

Clinical Trial Conditions for ZERBAXA

Condition Name

Condition Name for ZERBAXA
Intervention	Trials
Pharmacokinetics	2
Healthy Volunteers	1
Hematologic Cancer	1

Condition MeSH

Condition MeSH for ZERBAXA
Intervention	Trials
Pseudomonas Infections	2
Neutropenia	1
Infections	1

Clinical Trial Locations for ZERBAXA

Trials by Country

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−

Trials by Country for ZERBAXA
Location	Trials
United States	6
France	1
Australia	1
Qatar	1

Trials by US State

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−

Trials by US State for ZERBAXA
Location	Trials
Connecticut	2
Texas	1
Pennsylvania	1
North Carolina	1
Indiana	1

Clinical Trial Progress for ZERBAXA

Clinical Trial Phase

Clinical Trial Phase for ZERBAXA
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	1
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for ZERBAXA
Clinical Trial Phase	Trials
Completed	3
Recruiting	1
Terminated	1

Clinical Trial Sponsors for ZERBAXA

Sponsor Name

Sponsor Name for ZERBAXA
Sponsor	Trials
Merck Sharp & Dohme Corp.	3
Indiana University Health	1
The University of Queensland	1

Sponsor Type

Sponsor Type for ZERBAXA
Sponsor	Trials
Other	13
Industry	5

ZERBAXA: Clinical Trials, Market Analysis, and Projections

Introduction to ZERBAXA

ZERBAXA, a combination antibiotic consisting of ceftolozane and tazobactam, has been a significant player in the treatment of various bacterial infections. Developed by Merck, this drug has undergone extensive clinical trials and has shown promising results in several indications.

Clinical Trials Overview

Ventilated Nosocomial Pneumonia (VNP)

One of the key clinical trials for ZERBAXA was the ASPECT-NP trial, which evaluated its efficacy and safety in treating adult patients with ventilated nosocomial pneumonia. This randomized, double-blind, multi-center Phase 3 trial compared ZERBAXA (3g dose: 2g ceftolozane/1g tazobactam) to meropenem (1g dose) administered intravenously every eight hours for 8-14 days.

• Primary and Secondary Endpoints: The trial demonstrated non-inferiority of ZERBAXA to meropenem in the primary endpoint of 28-day all-cause mortality and the key secondary endpoint of clinical cure at test-of-cure (TOC) in the intent-to-treat (ITT) population. The mortality rates were 24.0% for ZERBAXA and 25.3% for meropenem, with a weighted proportion difference of 1.1%[1].
• Adverse Events: Treatment-emergent adverse events were reported in 85.9% of ZERBAXA-treated patients and 83.3% of meropenem-treated patients. The most common adverse events with ZERBAXA included abnormal liver function tests and Clostridium difficile-associated diarrhea[1].

Complicated Intra-Abdominal Infections (cIAI) and Complicated Urinary Tract Infections (cUTI)

ZERBAXA has also been evaluated in Phase 3 comparator-controlled clinical trials for cIAI and cUTI. These trials involved a total of 1015 patients treated with ZERBAXA (1.5g every 8 hours) and compared it to levofloxacin or meropenem.

• Efficacy and Safety: The trials showed that ZERBAXA was effective in treating these infections, with clinical cure rates comparable to the comparator drugs. However, there were instances of treatment discontinuation due to adverse events, particularly renal impairment[4].

Market Analysis

Current Market Performance

As of the third quarter of 2024, Merck's overall pharmaceutical sales have seen a significant increase, driven largely by the success of KEYTRUDA and other new launches. While ZERBAXA is not explicitly highlighted in Merck's recent financial reports, its inclusion in the broader antibiotic market contributes to the company's pharmaceutical revenue.

• Revenue Growth: Merck's total worldwide sales were $16.7 billion in the third quarter of 2024, a 4% increase from the third quarter of 2023. The pharmaceutical segment, which includes ZERBAXA, saw a 5% growth driven by oncology and cardiovascular products, though partially offset by declines in other areas[2].

Market Potential

ZERBAXA's market potential is significant given its broad spectrum of activity against Gram-negative bacteria, including multi-drug resistant strains.

• Indications: ZERBAXA is indicated for the treatment of cUTI, cIAI, and hospital-acquired bacterial pneumonia (HABP), including ventilator-associated bacterial pneumonia (VABP). It is also under development for additional indications such as uncomplicated pyelonephritis and nosocomial pneumonia in pediatric patients[3].
• Competitive Landscape: The antibiotic market is highly competitive, but ZERBAXA's unique combination and efficacy profile position it as a valuable option for treating serious bacterial infections.

Projections and Future Outlook

Regulatory Approvals

Based on the positive results from the ASPECT-NP trial, Merck has submitted supplemental new drug applications to the FDA and EMA seeking approval for ZERBAXA in the treatment of ventilated nosocomial pneumonia. This potential new indication could significantly expand ZERBAXA's market reach[1].

Market Expansion

• Geographical Expansion: ZERBAXA is expected to see increased adoption globally, particularly in regions with high incidence rates of resistant bacterial infections.
• Pediatric Indications: The drug's development for nosocomial pneumonia in pediatric patients could open up a new market segment, further increasing its revenue potential[3].

Challenges and Opportunities

• Resistance and Safety Concerns: The ongoing challenge of antibiotic resistance and the need for careful monitoring of adverse events, such as renal impairment, will continue to influence ZERBAXA's market trajectory.
• Competition and Pricing: The competitive landscape and pricing strategies will play crucial roles in determining ZERBAXA's market share and revenue growth.

Key Takeaways

• Clinical Efficacy: ZERBAXA has demonstrated non-inferiority to meropenem in treating ventilated nosocomial pneumonia and is effective in cIAI and cUTI.
• Market Potential: With its broad spectrum of activity and potential new indications, ZERBAXA has significant market potential.
• Regulatory Approvals: Pending approvals for new indications could expand its market reach.
• Challenges: Ongoing challenges include antibiotic resistance and adverse event monitoring.

FAQs

What is ZERBAXA used for?

ZERBAXA is used for the treatment of complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired bacterial pneumonia (HABP), including ventilator-associated bacterial pneumonia (VABP).

What were the key findings of the ASPECT-NP trial?

The ASPECT-NP trial demonstrated that ZERBAXA was non-inferior to meropenem in terms of 28-day all-cause mortality and clinical cure at test-of-cure (TOC) in patients with ventilated nosocomial pneumonia.

What are the common adverse events associated with ZERBAXA?

Common adverse events include abnormal liver function tests, Clostridium difficile-associated diarrhea, and renal impairment.

Is ZERBAXA approved for pediatric use?

ZERBAXA is currently under development for the treatment of nosocomial pneumonia in pediatric patients but is not yet approved for this indication.

How does ZERBAXA fit into Merck's overall pharmaceutical portfolio?

ZERBAXA contributes to Merck's pharmaceutical revenue, although its specific sales figures are not separately highlighted in recent financial reports. It is part of Merck's broader antibiotic offerings.

Sources

1. Merck News: Results of Phase 3 Trial Evaluating Merck's ZERBAXA® (ceftolozane and tazobactam) versus Meropenem for Treatment of Adult Patients with Ventilated Nosocomial Pneumonia (VNP) to be Presented at ECCMID 2019.
2. Merck Financial Results: Merck Announces Third-Quarter 2024 Financial Results.
3. GlobalData: Net Present Value Model: Zerbaxa - GlobalData.
4. Merck Connect: Adverse Reactions for ZERBAXA® (ceftolozane and tazobactam).