Telavancin Pharmacokinetics in Cystic Fibrosis Patients

NCT03172793 | Completed Phase 4 FDA Drug

• 1 other identifier: HHC-2017-0093
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

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.

Conditions

Cystic Fibrosis

Keywords

telavancin; lipoglycopeptide; MRSA; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  4 days

Study Arms (3)

Telavancin injection Dose 1 (7.5mg/kg)

EXPERIMENTAL

The pharmacokinetics and tolerability of telavancin 7.5mg/kg q24h will be measured in 6 participants.

Drug: Telavancin Injection

Telavancin injection Dose 2 (10mg/kg)

EXPERIMENTAL

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

Telavancin injection Dose 3 (TBD)

EXPERIMENTAL

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

Interventions

Telavancin Injection DRUG

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

Also known as: Vibativ

Telavancin injection Dose 1 (7.5mg/kg); Telavancin injection Dose 2 (10mg/kg); Telavancin injection Dose 3 (TBD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joseph L. Kuti, PharmD: lead
• Cumberland Pharmaceuticals, Inc.: collaborator

Study Sites (5)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

St. Christophers Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

University of Pittsburgh Medical Center Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• 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):e01914-19. doi: 10.1128/AAC.01914-19. Print 2019 Dec 20.

  PMID: 31685468 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

telavancin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Joseph L Kuti, PharmD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Director, CAIRD

Model Details: 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.

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: June 1, 2017
• Study Start: August 8, 2017
• Primary Completion: April 17, 2019
• Study Completion: April 17, 2019
• Last Updated: October 24, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)