Telavancin Pharmacokinetics in Cystic Fibrosis Patients

Cystic Fibrosis Clinical Trial

Official title:

Pharmacokinetics and Tolerability of Telavancin at Differing Dosing Regimens in Cystic Fibrosis Adults Admitted With Acute Pulmonary Exacerbations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03172793
• Other study ID #: HHC-2017-0093
• Status: Completed
• Phase: Phase 4
• Start date: August 8, 2017
• Est. completion date: April 17, 2019

Study information

• Verified date: October 2019
• Source: Hartford Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Due to emerging resistance, new antibiotic options are needed to treat CF acute pulmonary exacerbations caused by methicillin resistant Staphylococcus aureus (MRSA). There is established evidence that adult patients with cystic fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Telavancin is a lipoglycopeptide antibiotic that has activity against gram-positive bacteria including MRSA. This study will determine the pharmacokinetics and tolerability of telavancin in 18 adult CF patients admitted for a pulmonary exacerbation at 1 of 4 participating hospitals in the US.

Description:

Each participant will receive 3 doses of intravenous telavancin administered every 24 hours. Up to three different doses of telavancin will be studied (n=6 per group). Blood samples will be collected throughout the study to determine the pharmacokinetics of telavancin. Each group will proceed after measurement of safety, tolerability, and pharmacokinetics of the lower dose group before it.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 17, 2019
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or older

• Documented diagnosis of CF

• Acute pulmonary exacerbation as the primary reason for admission to the hospital with requirement to receive systemic antibiotic treatment, as defined by treating provider

• If female, subjects must be non-pregnant and non-lactating. Females can be either not of a child-bearing potential or if of a child-bearing potential, on acceptable modes of birth control such as abstinence from sexual intercourse, oral/parenteral contraceptives, or barrier method

Exclusion Criteria:

• History of any moderate or severe hypersensitivity or allergic reaction to telavancin or any component of telavancin, or any glycopeptide (e.g., vancomycin) antibiotic (a history of red man syndrome with vancomycin is not an exclusion criteria)

• History of any solid organ transplantation within the last 12 months

• Moderate to severe renal dysfunction defined as a creatinine clearance (CLCR) < 50 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis

• Oliguria (urine output < 0.4 mL/kg/hr for at least 12 hours, up to a total of <20 mL/hr) or significant alterations in fluid/electrolyte homeostasis in a 72 hour window before enrollment with a history of renal compromise

• A hemoglobin less than 8 gm/dl at baseline

• Anticipated length of hospital stay less than 4 days, which would prevent completion of dose administration and pharmacokinetic sampling

• Receiving intravenous vancomycin at the time of enrollment or anticipation of requiring intravenous vancomycin during study participation (Note. Other antibiotics targeting Gram-positive bacteria such as MRSA are permitted)

• Receiving an anticoagulant AND requires specific coagulation testing (prothrombin time/international normalized ratio, activated partial thromboplastin time, activated clotting time, or coagulation based factor x activity assay) within 24 hours of receiving a telavancin dose (Note. Although telavancin does not interfere with coagulation, it may interfere with some assays used to monitor coagulation)

• Requirement of concomitant administration of agents containing a cyclodextrin solubilizer such as intravenous voriconazole or itraconazole

• Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator)

• Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data

• Planned or prior participation in any other interventional drug study within 30 days

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Telavancin Injection
Receive 3 doses of telavancin as described in arm/groups, followed by collection of blood for pharmacokinetic analyses.

Locations

Country	Name	City	State
United States	Hartford Hospital	Hartford	Connecticut
United States	IU Health University Hospital	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	St. Christophers Hospital for Children	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center Shadyside	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Joseph L. Kuti, PharmD	Cumberland Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Telavancin Clearance	This outcome measures the total body clearance (L/hr) of telavancin over the 4 day study.	1, 24, 25, 48, 49-49.08, 49.25-49.5, 50-51, 52-53, 55-56, 57-61, and 72 hours after start of dosing.
Primary	Telavancin Volume of Distribution	This outcome measures the volume of distribution (L) of telavancin over the 4 day study.	1, 24, 25, 48, 49-49.08, 49.25-49.5, 50-51, 52-53, 55-56, 57-61, and 72 hours after start of dosing.
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	This outcome measures the safety and tolerability of telavancin over the 4 day study with specific attention to changes in chemistry, complete blood count, and liver function tests before and after treatment, as well as any participant reported adverse events.	4 days