Cystic Fibrosis
Conditions
Brief summary
The proposed study is designed to characterize the pharmacokinetics of intravenous and oral tedizolid in patients with Cystic Fibrosis.
Detailed description
Recent epidemiological studies have demonstrated that the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the airways of patients with CF is associated with more rapid lung function decline and a higher mortality. Tedizolid is a new antibiotic with potent activity against MRSA. Tedizolid is currently FDA approved for treatment of skin soft tissue infections with MRSA. The proposed study is designed to characterize the pharmacokinetics of intravenous and oral tedizolid in patients with CF.
Interventions
DRUGTedizolid PO
Participants will be randomized to receive tedizolid oral 200mg once daily for 3 days and crossed over to IV after a 1 week washout.
DRUGTedizolid IV
Participants will be randomized to receive tedizolid IV 200mg once daily for 3 days and crossed over to PO after a 1 week washout.
Sponsors
Merck Sharp & Dohme LLC
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CF based on positive sweat chloride or known CF mutation * Age \> 17 years * Able to spontaneously expectorate sputum
Exclusion criteria
* Any clinically significant laboratory abnormalities * Presence of an ongoing acute pulmonary exacerbation * Pregnancy * Serious past allergy to linezolid or tedizolid * No alcohol, nicotine, or caffeine-containing products during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) | 2 days | Cmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose |
| Area Under the Plasma Concentration Versus Time Curve (AUC) | 2 days | Area under the curve was calculated using samples collected at baseline (0 h) , 0.5, 1, 2, 3, 4, 8, 24, and 48 hours post-dose and using the equation AUC=Dose\*F/CL |
| Time to Peak Plasma Concentration (Tmax) | 2 days | Tmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose |
| Peak Sputum Concentration | 2 days | Peak sputum concentration was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose. |
| Area Under the Sputum Concentration Versus Time Curve (AUC) | 2 days | AUC was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose |
| Time to Peak Sputum Concentration (Tmax) | 2 days | Tmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose. Tmax was derived from pooled sputum data due to sparse samples and therefore do not have standard deviations. |
Countries
United States
Participant flow
Pre-assignment details
This was a cross-over study where patients with CF received tedizolid 200mg IV or PO once daily for 3 doses followed by a minimum 2 day washout and receipt of the remaining dosage form.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants were randomized to receive either tedizolid oral 200 mg tablet or IV 200 mg once daily for 3 days and crossed over to either IV or PO after a minimum of 2 day washout period | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 27.27 years STANDARD_DEVIATION 4.78 |
| Body Mass Index | 21.72 kg/m2 STANDARD_DEVIATION 3.6 |
| Creatinine Clearance | 147.6 mL/min STANDARD_DEVIATION 32.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 1 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC)
Area under the curve was calculated using samples collected at baseline (0 h) , 0.5, 1, 2, 3, 4, 8, 24, and 48 hours post-dose and using the equation AUC=Dose\*F/CL
Time frame: 2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tedizolid PO | Area Under the Plasma Concentration Versus Time Curve (AUC) | 22.1 mg*h/mL | Standard Deviation 5.72 |
| Tedizolid IV | Area Under the Plasma Concentration Versus Time Curve (AUC) | 20.7 mg*h/mL | Standard Deviation 3.92 |
Primary
Area Under the Sputum Concentration Versus Time Curve (AUC)
AUC was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose
Time frame: 2 days
Population: One patient could not produce sputum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tedizolid PO | Area Under the Sputum Concentration Versus Time Curve (AUC) | 15.04 mg*h/mL | Standard Deviation 8.92 |
| Tedizolid IV | Area Under the Sputum Concentration Versus Time Curve (AUC) | 13.53 mg*h/mL | Standard Deviation 7.203 |
Primary
Peak Plasma Concentration (Cmax)
Cmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose
Time frame: 2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tedizolid PO | Peak Plasma Concentration (Cmax) | 2.22 mg/liter | Standard Deviation 0.745 |
| Tedizolid IV | Peak Plasma Concentration (Cmax) | 2.92 mg/liter | Standard Deviation 0.624 |
Primary
Peak Sputum Concentration
Peak sputum concentration was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose.
Time frame: 2 days
Population: One patient could not produce sputum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tedizolid PO | Peak Sputum Concentration | 1.08 mg/liter | Standard Deviation 0.6 |
| Tedizolid IV | Peak Sputum Concentration | 1.196 mg/liter | Standard Deviation 0 |
Primary
Time to Peak Plasma Concentration (Tmax)
Tmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose
Time frame: 2 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tedizolid PO | Time to Peak Plasma Concentration (Tmax) | 2.5 hours | Standard Deviation 1.33 |
| Tedizolid IV | Time to Peak Plasma Concentration (Tmax) | 1.36 hours | Standard Deviation 0.369 |
Primary
Time to Peak Sputum Concentration (Tmax)
Tmax was calculated using data collected at 0, 0.5, 1, 2, 3, 4, 8, 24, 48 hours post-dose. Tmax was derived from pooled sputum data due to sparse samples and therefore do not have standard deviations.
Time frame: 2 days
Population: One patient could not produce sputum
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tedizolid PO | Time to Peak Sputum Concentration (Tmax) | 4 hours | Standard Deviation 0 |
| Tedizolid IV | Time to Peak Sputum Concentration (Tmax) | 3 hours | Standard Deviation 0 |