Healthy
Conditions
Keywords
Delafloxacin, Baxdela, BARDA, Bioavailability, Taste-masked
Brief summary
This study will compare the bioavailability of a novel powder for oral suspension formulation of delafloxacin, intended for treatment of community acquired bacterial pneumonia, to that of the licensed delafloxacin oral tablet in healthy adults.
Interventions
DRUGDelafloxacin
Delafloxacin tablet
DRUGDelafloxacin Powder
Delafloxacin powder for oral suspension formulation
Sponsors
Biomedical Advanced Research and Development Authority
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Must agree to adhere to the protocol-specified contraception requirements. * Body mass index of 18.0 to 32.0 kilograms (kg)/meter squared as measured at screening. * Weight ≥50 kg at screening. Key
Exclusion criteria
* Any history of hypersensitivity to delafloxacin or any other fluoroquinolones or previous history of tendon disorders related to fluoroquinolone administration. * History of clinically significant cardiovascular, renal, hepatic, respiratory, or particularly gastrointestinal disease. * Participant has a medical condition that may adversely affect taste or smell activity including but not limited to mouth ulcers, significant gum disease, and respiratory and/or sinus infection or cold. * Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by the Investigator. Participants with Gilbert's Syndrome are not allowed. * Participants who do not agree to eat a high-fat breakfast. Note: Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Mean Concentration Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Delafloxacin Powder Compared to Oral Delafloxacin Tablet | Pre-dose on Day 1, up to 24 hours post-dose | Blood samples were obtained at protocol-specified timepoints. Results reported as nanograms\*hour/milliliter (ng\*h/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Delafloxacin Powder | Pre-dose on Day 1, up to 48 hours post-dose | Blood samples were obtained at protocol-specified timepoints. Results reported as nanograms/milliliter (ng/mL). |
| Area Under the Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-last) of Delafloxacin Powder | Pre-dose on Day 1, up to 48 hours post-dose | Blood samples were obtained at protocol-specified timepoints. Results reported as ng\*h/mL. |
| Number of Participants Experiencing Treatment-emergent Adverse Events | Day 1 through Day 6 | An adverse event (AE) was any untoward medical occurrence in a participant that occurred either before dosing or once an investigational medicinal product (IMP) had been administered, including occurrences which were not necessarily caused by or related to that product. Treatment-emergent adverse events were AEs that commenced during/after the first administration of IMP or commenced before first administration of IMP, that is, a pre-dose AE or existing medical condition, but worsened in intensity during exposure to IMP. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Countries
United Kingdom
Participant flow
Recruitment details
During the interim decision meeting following dosing of Regimen A and Regimen B, it was decided not to proceed with Regimen C and Regimen D of the study, and subsequently the decision was made to terminate the study early. Therefore, data were only collected for Regimen A and Regimen B.
Participants by arm
| Arm | Count |
|---|---|
| Regimen A Then B: Delafloxacin Tablet Then Powder Participants received delafloxacin tablet in a fasted state (Regimen A), followed by delafloxacin powder in a fasted state (Regimen B). | 8 |
| Regimen B Then A: Delafloxacin Powder Then Tablet Participants received delafloxacin powder in a fasted state (Regimen B), followed by delafloxacin tablet in a fasted state (Regimen A). | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Regimen B Then A: Delafloxacin Powder Then Tablet | Total | Regimen A Then B: Delafloxacin Tablet Then Powder |
|---|---|---|---|
| Age, Continuous | 36.0 years STANDARD_DEVIATION 14.4 | 35.6 years STANDARD_DEVIATION 12.1 | 35.3 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 7 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 16 | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Mean Concentration Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Delafloxacin Powder Compared to Oral Delafloxacin Tablet
Blood samples were obtained at protocol-specified timepoints. Results reported as nanograms\*hour/milliliter (ng\*h/mL).
Time frame: Pre-dose on Day 1, up to 24 hours post-dose
Population: Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study drug and who were evaluable for this outcome measure at the specified timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen A: Delafloxacin Tablet | Area Under the Mean Concentration Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Delafloxacin Powder Compared to Oral Delafloxacin Tablet | 15700 ng*h/mL | Geometric Coefficient of Variation 26.9 |
| Regimen B: Delafloxacin Powder | Area Under the Mean Concentration Time Curve From Time 0 to 24 Hours Post-dose (AUC0-24) of Delafloxacin Powder Compared to Oral Delafloxacin Tablet | 8120 ng*h/mL | Geometric Coefficient of Variation 33.9 |
Comparison: Results obtained from mixed effects model of natural log transformed pharmacokinetic parameters including terms for regimen, period and sequence fitted as fixed effects and subject nested within sequence fitted as a random effect.90% CI: [45.71, 58.43]
Secondary
Area Under the Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-last) of Delafloxacin Powder
Blood samples were obtained at protocol-specified timepoints. Results reported as ng\*h/mL.
Time frame: Pre-dose on Day 1, up to 48 hours post-dose
Population: Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study drug and who were evaluable for this outcome measure at the specified timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen A: Delafloxacin Tablet | Area Under the Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-last) of Delafloxacin Powder | 8450 ng*h/mL | Geometric Coefficient of Variation 33.5 |
Secondary
Maximum Observed Concentration (Cmax) of Delafloxacin Powder
Blood samples were obtained at protocol-specified timepoints. Results reported as nanograms/milliliter (ng/mL).
Time frame: Pre-dose on Day 1, up to 48 hours post-dose
Population: Pharmacokinetic Analysis Set: all participants who received at least 1 dose of study drug and who were evaluable for this outcome measure at the specified timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen A: Delafloxacin Tablet | Maximum Observed Concentration (Cmax) of Delafloxacin Powder | 1850 ng/mL | Geometric Coefficient of Variation 33.4 |
Secondary
Number of Participants Experiencing Treatment-emergent Adverse Events
An adverse event (AE) was any untoward medical occurrence in a participant that occurred either before dosing or once an investigational medicinal product (IMP) had been administered, including occurrences which were not necessarily caused by or related to that product. Treatment-emergent adverse events were AEs that commenced during/after the first administration of IMP or commenced before first administration of IMP, that is, a pre-dose AE or existing medical condition, but worsened in intensity during exposure to IMP. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Day 1 through Day 6
Population: Safety Analysis Set: all participants who received any amount of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regimen A: Delafloxacin Tablet | Number of Participants Experiencing Treatment-emergent Adverse Events | 2 Participants |
| Regimen B: Delafloxacin Powder | Number of Participants Experiencing Treatment-emergent Adverse Events | 5 Participants |