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Telavancin Pharmacokinetics in Cystic Fibrosis Patients

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ClinicalTrials.gov Identifier: NCT03172793
Recruitment Status : Recruiting
First Posted : June 1, 2017
Last Update Posted : May 23, 2018
Sponsor:
Collaborator:
Theravance Biopharma, US, Inc.
Information provided by (Responsible Party):
Joseph Kuti, Hartford Hospital

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 Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : March 30, 2019
Estimated Study Completion Date : June 30, 2019


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




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.



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03172793


Contacts
Contact: Joseph L Kuti, PharmD 869-972-3612 joseph.kuti@hhchealth.org

Locations
United States, Arizona
Banner University of Arizona Medical Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Hanna Phan, PharmD    520-626-0050    hphan@pharmacy.arizona.edu   
United States, Connecticut
Hartford Hospital Recruiting
Hartford, Connecticut, United States, 06102
Contact: Joseph L Kuti, PharmD       joseph.kuti@hhchealth.org   
United States, Indiana
IU Health University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Rebecca Pettit, PharmD       rpettit1@IUHealth.org   
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Rebecca Pettit, PharmD       rpettit1@IUHealth.org   
United States, Pennsylvania
St. Christophers Hospital for Children Recruiting
Philadelphia, Pennsylvania, United States, 19134
Contact: Jeffrey Cies, PharmD       jeffrey.cies@tenethealth.com   
University of Pittsburgh Medical Center Shadyside Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Louise-Marie Oleksiuk, PharmD       gillislm@upmc.edu   
Sponsors and Collaborators
Joseph Kuti
Theravance Biopharma, US, Inc.
Investigators
Principal Investigator: Joseph L Kuti, PharmD Hartford Hospital

Responsible Party: Joseph Kuti, Associate Director, CAIRD, Hartford Hospital
ClinicalTrials.gov Identifier: NCT03172793     History of Changes
Other Study ID Numbers: HHC-2017-0093
First Posted: June 1, 2017    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 2018
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 Kuti, 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