Cystic Fibrosis
Conditions
Keywords
telavancin, lipoglycopeptide, MRSA, pharmacokinetics
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.
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.
Interventions
Receive 3 doses of telavancin as described in arm/groups, followed by collection of blood for pharmacokinetic analyses.
Sponsors
Cumberland Pharmaceuticals, Inc.
Joseph L. Kuti, PharmD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Telavancin Clearance | 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. |
| Telavancin Volume of Distribution | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 | 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. |
Countries
United States
Outcome results
None listed