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Relative Exposure and Safety Study of a New Formulation of Oritavancinin in ABSSSI Patients

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ClinicalTrials.gov Identifier: NCT03873987
Recruitment Status : Completed
First Posted : March 14, 2019
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Melinta Therapeutics, Inc.

Brief Summary:
This study is being conducted to evaluate the pharmacokinetic (PK) and safety of a new formulation versus the approved oritavancin formulation in subjects with acute bacterial skin and skin structure infection (ABSSSI). The new formulation adjusts the infusion time, concentration and reconstitution/administration solutions of a single 1200 mg intravenous (IV) infusion of oritavancin

Condition or disease Intervention/treatment Phase
Acute Bacterial Skin and Skin Structure Infection Drug: Current Formulation of Oritavancin Drug: New Formulation of Oritavancin Phase 1

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 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 a new formulation of oritavancin 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : July 16, 2019
Actual Primary Completion Date : August 27, 2019
Actual Study Completion Date : September 4, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oritavancin

Arm Intervention/treatment
Active Comparator: 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.
Drug: Current Formulation of Oritavancin
Current formulation of oritavancin (3 hour infusion of 1200 mg in 1000 ml of D5W)
Other Name: Orbactiv

Experimental: 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.
Drug: New Formulation of Oritavancin
New formulation of oritavancin (1 hour infusion of 1200 mg in 250 ml of saline)




Primary Outcome Measures :
  1. Relative exposure of AUC of the new formulation to the approved formulation [ Time Frame: 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)

  2. Relative exposure of AUC of the new formulation to the approved formulation [ Time Frame: 168 hours (Day 8) ]
    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 :
  1. Safety and tolerability of the new formulation of oritavancin assessed by the occurrence of abnormal clinical laboratory parameters [ Time Frame: 336 hours (Day 15) ]
  2. Safety and tolerability of the new formulation of oritavancin assessed by the occurrence of adverse events (AEs) [ Time Frame: 336 hours (Day 15) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03873987


Locations
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United States, California
ML-ORI-102 Study Site
Chula Vista, California, United States, 91911
ML-ORI-102 Study Site
La Mesa, California, United States, 91942
United States, Illinois
ML-ORI-102 Study Site
Burr Ridge, Illinois, United States, 60527
United States, New Jersey
ML-ORI-102 Study Site
Somers Point, New Jersey, United States, 08244
Sponsors and Collaborators
Melinta Therapeutics, Inc.
Investigators
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Study Director: Sue K Cammarata, MD Melinta Therapeutics, Inc.

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Responsible Party: Melinta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03873987     History of Changes
Other Study ID Numbers: ML-ORI-102
First Posted: March 14, 2019    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Skin Diseases, Bacterial
Bacterial Infections
Skin Diseases, Infectious
Infection
Skin Diseases
Oritavancin
Anti-Bacterial Agents
Anti-Infective Agents