Acute Bacterial Skin and Skin Structure Infection
Conditions
Brief summary
This study is being conducted to evaluate the pharmacokinetic (PK) and safety of Kimyrsa versus the approved oritavancin formulation in subjects with acute bacterial skin and skin structure infection (ABSSSI). Kimyrsa adjusts the infusion time, concentration and reconstitution/administration solutions of a single 1200 mg intravenous (IV) infusion of oritavancin
Detailed description
Single IV dose oritavancin (1200 mg) has been approved in the U.S. for the treatment of adult patients with ABSSSI caused or suspected to be caused by Gram-positive microorganisms. The current study is being conducted to evaluate the relative exposure, PK and safety of a new formulation of oritavancin, Kimyrsa, by adjusting infusion time, concentration and reconstitution/administration solutions of a single 1200 mg IV infusion of oritavancin in adult subjects with ABSSSI. Fifty (50) subjects will be administered the currently approved formulation of oritavancin, using the approved dosing regimen in which Sterile Water for Injection (SWFI) is the reconstituting agent and Dextrose 5% in Water (D5W) is used for further dilution to a total volume of 1000 mL. This formulation will be infused per the approved label over 3 hours. An additional 50 subjects will be administered Kimyrsa which contains hydroxypropyl-β-cyclodextrin (HPβCD). This formulation will be reconstituted with SWFI and further diluted in 0.9% sodium chloride (saline) to a total volume of 250 mL. This formulation will be infused over 60 minutes.
Interventions
DRUGCurrent Formulation of Oritavancin
Current formulation of oritavancin (3 hour infusion of 1200 mg in 1000 ml of D5W)
DRUGKimyrsa
New formulation of oritavancin (1 hour infusion of 1200 mg in 250 ml of saline)
Sponsors
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects may be included in the study if they meet all of the following criteria: 1. Subject must be 18 years of age or older, male or female, and of any race. 2. Subject must give written informed consent before initiation of any study-related procedures. 3. Diagnosis of ABSSSI (wound infections, cellulitis/erysipelas, or cutaneous abscess) suspected or confirmed to be caused by a Gram-positive pathogen requiring IV therapy. 4. If female, the subject is surgically sterile, postmenopausal, or, if of childbearing potential, agrees to use at least 2 highly effective methods of birth control (e.g. prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier methods, abstinence) for the duration of the study until 60 days after study drug administration, or male partner sterilization alone. 5. Subject must express a commitment to comply with all study visits, procedures and requirements for the duration of the study.
Exclusion criteria
Subjects will be excluded from the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Exposure of AUC of the New Formulation to the Approved Formulation | 72 hours | Relative exposure of AUC of the new formulation to the approved formulation of oritavancin based on area under the plasma concentration-time curve from time zero to 72 hr (AUC0-72) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Treatment Emergent Adverse Event (TEAE) | 336 hours (Day 15) | Number of subjects with at least one treatment emergent adverse event (TEAE) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Current Formulation of Oritavancin Three single-use vials, each containing 400 mg (1200 mg total) of oritavancin diphosphate (as the free base) and the inactive component mannitol. Oritavancin vials will be reconstituted with SWFI and further diluted in D5W for a total volume of 1000 mL and infused intravenously over 3 hours.
Current Formulation of Oritavancin: Current formulation of oritavancin (3 hour infusion of 1200 mg in 1000 ml of D5W) | 52 |
| New Formulation of Oritavancin A single vial containing 1200 mg of oritavancin, HPβCD, and mannitol. Oritavancin vials will be reconstituted with SWFI and further diluted with 0.9% sodium chloride for a total volume of 250 mL and infused intravenously over 1 hour.
New Formulation of Oritavancin: New formulation of oritavancin (1 hour infusion of 1200 mg in 250 ml of saline) | 50 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | staff was unable to start a new IV line | 1 | 0 |
Baseline characteristics
| Characteristic | Current Formulation of Oritavancin | Total | New Formulation of Oritavancin |
|---|---|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 12.1 | 44.3 years STANDARD_DEVIATION 12.6 | 42.1 years STANDARD_DEVIATION 12.7 |
| Body Mass Index (BMI) | 27.3 kg/m2 STANDARD_DEVIATION 6 | 28.5 kg/m2 STANDARD_DEVIATION 7.4 | 29.7 kg/m2 STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 42 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 60 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 91 Participants | 46 Participants |
| Region of Enrollment United States | 52 participants | 102 participants | 50 participants |
| Sex: Female, Male Female | 15 Participants | 35 Participants | 20 Participants |
| Sex: Female, Male Male | 37 Participants | 67 Participants | 30 Participants |
| Weight | 80.8 kg STANDARD_DEVIATION 19.5 | 84.7 kg STANDARD_DEVIATION 23.7 | 88.7 kg STANDARD_DEVIATION 26.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 50 |
| other Total, other adverse events | 31 / 52 | 24 / 50 |
| serious Total, serious adverse events | 1 / 52 | 2 / 50 |
Outcome results
Primary
Relative Exposure of AUC of the New Formulation to the Approved Formulation
Relative exposure of AUC of the new formulation to the approved formulation of oritavancin based on area under the plasma concentration-time curve from time zero to 72 hr (AUC0-72)
Time frame: 72 hours
Population: PK Population: all subjects who have received the full dose of oritavancin and have any valid samples measured for study drug levels
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Orbactiv | Relative Exposure of AUC of the New Formulation to the Approved Formulation | 1470 h*µg/mL | Geometric Coefficient of Variation 39.7 |
| Kimrysa | Relative Exposure of AUC of the New Formulation to the Approved Formulation | 1460 h*µg/mL | Geometric Coefficient of Variation 35.1 |
Primary
Relative Exposure of AUC of the New Formulation to the Approved Formulation
Relative exposure of AUC of the new formulation to the approved formulation of oritavancin based on area under the plasma concentration-time curve from time zero to 168 hr (AUC0-168).
Time frame: 168 hours (Day 8)
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Orbactiv | Relative Exposure of AUC of the New Formulation to the Approved Formulation | 1760 h*µg/mL | Geometric Coefficient of Variation 41.4 |
| Kimrysa | Relative Exposure of AUC of the New Formulation to the Approved Formulation | 1750 h*µg/mL | Geometric Coefficient of Variation 35 |
Secondary
Number of Subjects With at Least One Treatment Emergent Adverse Event (TEAE)
Number of subjects with at least one treatment emergent adverse event (TEAE)
Time frame: 336 hours (Day 15)
Population: Safety analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Orbactiv | Number of Subjects With at Least One Treatment Emergent Adverse Event (TEAE) | 31 Participants |
| Kimrysa | Number of Subjects With at Least One Treatment Emergent Adverse Event (TEAE) | 24 Participants |