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Relative Exposure and Safety Study of Kimyrsa in ABSSSI Patients

Primary Purpose

Acute Bacterial Skin and Skin Structure Infection

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Current Formulation of Oritavancin
Kimyrsa
Sponsored by
Melinta Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Acute Bacterial Skin and Skin Structure Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 exclusion criteria apply prior to randomization:

  1. Infections associated with, or in close proximity to, a prosthetic device.
  2. Severe sepsis or refractory shock.
  3. Known or suspected bacteremia at time of screening.
  4. ABSSSI due to or associated with any of the following:

    1. Infections suspected or documented to be caused by only Gram-negative pathogens (i.e., infections acquired during prolonged admission in hospital or long-term care facilities).
    2. Diabetic foot infections (infection extending distal to the malleoli in a subject with diabetes mellitus and peripheral neuropathy and/or vascular insufficiency or any ulceration of their foot).
    3. Concomitant infection at another site not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis).
    4. Infected burns.
    5. A primary infection secondary to a pre-existing skin disease with associated inflammatory changes such as atopic dermatitis, eczema, or hidradenitis suppurativa.
    6. Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous).
    7. Any evolving necrotizing process (i.e., necrotizing fasciitis), gangrene or infection suspected or proven to be caused by Clostridium species (e.g., crepitance on examination of the ABSSSI site and/or surrounding tissue(s) or radiographic evidence of subcutaneous gas in proximity to the infection).
    8. Infections known to be caused by an organism resistant to oritavancin.
    9. Catheter site infections.
  5. Treatment with investigational medicinal product within 30 days or 5 half-lives, whichever is longer, before enrollment and for the duration of the study.
  6. Subjects currently receiving anticoagulant therapy.
  7. Known liver function tests (LFTs) ≥ 3 times the upper limit of normal (ULN) or total bilirubin ≥ 2 times ULN.
  8. Any medical condition, which in the judgment of the Investigator, might interfere with the pharmacokinetics, distribution, metabolism, or excretion of the study drug.
  9. Any planned, major surgical procedure during the study period (Day 15).
  10. Subject is the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
  11. Known hypersensitivity to oritavancin, glycopeptides or HPβCD.
  12. Female subject who has a positive pregnancy test or is breastfeeding.
  13. Previous use of oritavancin or anticipated need to use a long acting glycopeptide during the study.

Sites / Locations

  • ML-ORI-102 Study Site
  • ML-ORI-102 Study Site
  • ML-ORI-102 Study Site
  • ML-ORI-102 Study Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Current Formulation of Oritavancin

Kimyrsa

Arm Description

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.

A single vial containing 1200 mg of oritavancin, HPβCD, and mannitol. Kimyrsa 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.

Outcomes

Primary Outcome Measures

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)
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).

Secondary Outcome Measures

Number of Subjects With at Least One Treatment Emergent Adverse Event (TEAE)
Number of subjects with at least one treatment emergent adverse event (TEAE)

Full Information

First Posted
March 11, 2019
Last Updated
March 18, 2021
Sponsor
Melinta Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03873987
Brief Title
Relative Exposure and Safety Study of Kimyrsa in ABSSSI Patients
Official Title
A Randomized, Open-label, PK and Safety Study to Evaluate the Relative Exposure and Safety of a New Formulation vs the Approved Formulation of a Single 1200 mg IV Dose of ORBACTIV® (Oritavancin) in Subjects Being Treated for ABSSSI
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
July 16, 2019 (Actual)
Primary Completion Date
August 27, 2019 (Actual)
Study Completion Date
September 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Melinta Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Bacterial Skin and Skin Structure Infection

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
102 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Current Formulation of Oritavancin
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Kimyrsa
Arm Type
Experimental
Arm Description
A single vial containing 1200 mg of oritavancin, HPβCD, and mannitol. Kimyrsa 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.
Intervention Type
Drug
Intervention Name(s)
Current Formulation of Oritavancin
Other Intervention Name(s)
Orbactiv
Intervention Description
Current formulation of oritavancin (3 hour infusion of 1200 mg in 1000 ml of D5W)
Intervention Type
Drug
Intervention Name(s)
Kimyrsa
Intervention Description
New formulation of oritavancin (1 hour infusion of 1200 mg in 250 ml of saline)
Primary Outcome Measure Information:
Title
Relative Exposure of AUC of the New Formulation to the Approved Formulation
Description
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
Title
Relative Exposure of AUC of the New Formulation to the Approved Formulation
Description
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)
Secondary Outcome Measure Information:
Title
Number of Subjects With at Least One Treatment Emergent Adverse Event (TEAE)
Description
Number of subjects with at least one treatment emergent adverse event (TEAE)
Time Frame
336 hours (Day 15)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects may be included in the study if they meet all of the following criteria: Subject must be 18 years of age or older, male or female, and of any race. Subject must give written informed consent before initiation of any study-related procedures. Diagnosis of ABSSSI (wound infections, cellulitis/erysipelas, or cutaneous abscess) suspected or confirmed to be caused by a Gram-positive pathogen requiring IV therapy. 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. 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 exclusion criteria apply prior to randomization: Infections associated with, or in close proximity to, a prosthetic device. Severe sepsis or refractory shock. Known or suspected bacteremia at time of screening. ABSSSI due to or associated with any of the following: Infections suspected or documented to be caused by only Gram-negative pathogens (i.e., infections acquired during prolonged admission in hospital or long-term care facilities). Diabetic foot infections (infection extending distal to the malleoli in a subject with diabetes mellitus and peripheral neuropathy and/or vascular insufficiency or any ulceration of their foot). Concomitant infection at another site not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis). Infected burns. A primary infection secondary to a pre-existing skin disease with associated inflammatory changes such as atopic dermatitis, eczema, or hidradenitis suppurativa. Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous). Any evolving necrotizing process (i.e., necrotizing fasciitis), gangrene or infection suspected or proven to be caused by Clostridium species (e.g., crepitance on examination of the ABSSSI site and/or surrounding tissue(s) or radiographic evidence of subcutaneous gas in proximity to the infection). Infections known to be caused by an organism resistant to oritavancin. Catheter site infections. Treatment with investigational medicinal product within 30 days or 5 half-lives, whichever is longer, before enrollment and for the duration of the study. Subjects currently receiving anticoagulant therapy. Known liver function tests (LFTs) ≥ 3 times the upper limit of normal (ULN) or total bilirubin ≥ 2 times ULN. Any medical condition, which in the judgment of the Investigator, might interfere with the pharmacokinetics, distribution, metabolism, or excretion of the study drug. Any planned, major surgical procedure during the study period (Day 15). Subject is the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study. Known hypersensitivity to oritavancin, glycopeptides or HPβCD. Female subject who has a positive pregnancy test or is breastfeeding. Previous use of oritavancin or anticipated need to use a long acting glycopeptide during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sue K Cammarata, MD
Organizational Affiliation
Melinta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
ML-ORI-102 Study Site
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
ML-ORI-102 Study Site
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
ML-ORI-102 Study Site
City
Burr Ridge
State/Province
Illinois
ZIP/Postal Code
60527
Country
United States
Facility Name
ML-ORI-102 Study Site
City
Somers Point
State/Province
New Jersey
ZIP/Postal Code
08244
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Relative Exposure and Safety Study of Kimyrsa in ABSSSI Patients

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