Telavancin Pharmacokinetics in Cystic Fibrosis Patients

• ClinicalTrials.gov Identifier: NCT03172793
• Recruitment Status: Completed
• First Posted: June 1, 2017
• Last Update Posted: October 24, 2019
• Sponsor: Joseph L. Kuti, PharmD
• Collaborator: Cumberland Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Joseph L. Kuti, PharmD, Hartford Hospital

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Telavancin Injection	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This pharmacokinetic study uses a sequential, adaptive design to determine the pharmacokinetics and safety/tolerability of increasing weight based doses of telavancin. During Arm 1, participants will receive 7.5 mg/kg daily. Upon completion of data collection and assessment of safety/tolerability, Arm 2 participants will receiving 10 mg/kg daily. After completion of Arms 1 and 2, a preliminary pharmacokinetic and pharmacodynamic analysis will be conducted. These results, combined with the safety/tolerability of the 10mg/kg dose, will provide decision support to select a PK/PD optimized dose for Arm 3.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Pharmacokinetics and Tolerability of Telavancin at Differing Dosing Regimens in Cystic Fibrosis Adults Admitted With Acute Pulmonary Exacerbations
• Actual Study Start Date: August 8, 2017
• Actual Primary Completion Date: April 17, 2019
• Actual Study Completion Date: April 17, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Telavancin injection Dose 1 (7.5mg/kg); The pharmacokinetics and tolerability of telavancin 7.5mg/kg q24h will be measured in 6 participants.	Drug: Telavancin Injection; Receive 3 doses of telavancin as described in arm/groups, followed by collection of blood for pharmacokinetic analyses.; Other Name: Vibativ
Experimental: Telavancin injection Dose 2 (10mg/kg); After completion and analysis of 7.5mg/kg group, the next 6 participants will receive 10mg/kg q24h, and pharmacokinetics and tolerability will be measured.	Drug: Telavancin Injection; Receive 3 doses of telavancin as described in arm/groups, followed by collection of blood for pharmacokinetic analyses.; Other Name: Vibativ
Experimental: Telavancin injection Dose 3 (TBD); The third arm will enroll 6 participants to receive the following dose of telavancin q24h: 7.5, 10, 12.5, or 15 mg/kg. The final dose will be selected based on pharmacokinetic studies from first 12 participants, tolerability, and pharmacodynamic modeling.	Drug: Telavancin Injection; Receive 3 doses of telavancin as described in arm/groups, followed by collection of blood for pharmacokinetic analyses.; Other Name: Vibativ

Outcome Measures

Primary Outcome Measures :

1. Telavancin Clearance [ Time Frame: 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. ]
   This outcome measures the total body clearance (L/hr) of telavancin over the 4 day study.
2. Telavancin Volume of Distribution [ Time Frame: 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. ]
   This outcome measures the volume of distribution (L) of telavancin over the 4 day study.

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 4 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Connecticut

Hartford Hospital

Hartford, Connecticut, United States, 06102

United States, Indiana

IU Health University Hospital

Indianapolis, Indiana, United States, 46202

Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

United States, Pennsylvania

St. Christophers Hospital for Children

Philadelphia, Pennsylvania, United States, 19134

University of Pittsburgh Medical Center Shadyside

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

Joseph L. Kuti, PharmD

Cumberland Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Joseph L Kuti, PharmD; Hartford Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kidd JM, Sakon CM, Oleksiuk LM, Cies JJ, Pettit RS, Nicolau DP, Kuti JL. Pharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary Exacerbation. Antimicrob Agents Chemother. 2019 Dec 20;64(1). pii: e01914-19. doi: 10.1128/AAC.01914-19. Print 2019 Dec 20.

• Responsible Party: Joseph L. Kuti, PharmD, Associate Director, CAIRD, Hartford Hospital
• ClinicalTrials.gov Identifier: NCT03172793
• Other Study ID Numbers: HHC-2017-0093
• First Posted: June 1, 2017
• Last Update Posted: October 24, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Joseph L. Kuti, PharmD, Hartford Hospital:

telavancin; lipoglycopeptide; MRSA; pharmacokinetics

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Telavancin; Anti-Bacterial Agents; Anti-Infective Agents