A Study to Assess the Cardiac Safety of Oritavancin in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT01762839
First received: December 12, 2012
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

The purpose of the study is to generate cardiac safety data using a supratherapeutic oritavancin dose of 1600 mg.


Condition Intervention Phase
Healthy
Drug: Single-Dose IV Oritavancin Diphosphate
Drug: Placebo
Drug: Moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Design, Study With an Open-Label Positive-Control, to Assess the Cardiac Safety of Oritavancin in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Placebo-adjusted change from Baseline in QTcF [ Time Frame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time ] [ Designated as safety issue: Yes ]
    Placebo-adjusted change from baseline in QTcF (QTc with the Fridericia correction) between each treatment and placebo.


Secondary Outcome Measures:
  • Placebo-adjusted change from baseline in QTcB, HR, RR, PR, and QRS interval analyses. [ Time Frame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time ] [ Designated as safety issue: Yes ]
    Placebo-adjusted change from baseline in QTcB, HR, RR, PR, and QRS interval analyses.

  • Placebo adjusted change from Baseline in the appearance or worsening of ST, T and U-wave morphology. [ Time Frame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time ] [ Designated as safety issue: Yes ]
    Placebo adjusted change from baseline in the appearance or worsening of ST, T and U-wave morphology.

  • Effects on the QTc interval related to plasma concentration levels of oritavancin [ Time Frame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time ] [ Designated as safety issue: Yes ]
    Compare the effects on the QTc interval to the plasma levels of oritavancin using concentration-effect modeling

  • Evaluate the number of volunteers with adverse events or abnormalities in lab/urine results and safety ECGs as measures of safety and tolerability [ Time Frame: Day 0 through Day 7 ] [ Designated as safety issue: Yes ]
    Compare safety and tolerability in healthy volunteers after a single IV dose of 1600 mg oritavancin


Enrollment: 150
Study Start Date: January 2013
Study Completion Date: March 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oritavancin
Single-Dose IV Oritavancin Diphosphate
Drug: Single-Dose IV Oritavancin Diphosphate
Intravenous oritavancin will be administered via two dedicated, peripheral venous lines one in each arm. The infusion will last approximately 3 hours.
Other Name: Oritavancin Diphosphate
Placebo Comparator: Placebo
IV placebo
Drug: Placebo
IV placebo will be administered via two dedicated, peripheral venous lines one in each arm. The infusion will last approximately 3 hours.
Other Name: Placebo
Active Comparator: Moxifloxacin
Subjects randomized to the open label Moxifloxacin treatment arm will only receive a moxifloxacin tablet and will not receive a placebo infusion.
Drug: Moxifloxacin
Subjects randomized to the open label Moxifloxacin treatment arm will only receive a 400 mg moxifloxacin tablet and will not receive a placebo infusion.
Other Name: Avelox

Detailed Description:

This study will be a single-center, double-blind, randomized, placebo-controlled parallel design study with an open label positive-control moxifloxacin arm to evaluate the effect of supratherapeutic dose of oritavancin on the QT and QTc intervals.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Able to give written informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
  2. Healthy, male and female between 18 and 60 years old, BMI between 18 kg/m2 and 30 kg/m2
  3. In good health based upon results of medical history, physical examination, no clinically significant 12-lead ECG results, and laboratory test results.
  4. Serum magnesium and potassium levels within the normal range at screening.
  5. Agree to abstain from alcohol, caffeine-, and xanthine-containing products, all kind of energy drinks and the consumption of grapefruit juice and orange juice from 48 hours before study drug administration until completion of the follow-up visit.

Exclusion Criteria:

  1. History of immune-related hypersensitivity reaction to glycopeptides (such as vancomycin, televancin, daptomycin, or teicoplanin) or any of their excipients. Note: patients who have had histamine-like infusion reactions to a glycopeptide are not excluded
  2. A resting pulse rate < 50 beats per minute (bpm) or > 100 bpm
  3. Systolic blood pressure < 90 mmHg or diastolic blood pressure < 50 mmHg
  4. A QTcF >450 msec (males) or > 470 msec (females)
  5. Respiratory difficulties, or a history of asthma or chronic obstructive pulmonary disease
  6. Use of any prescription drug or over-the-counter (OTC) medications or herbal preparations within 14 days or 5-times the elimination half-life (whichever is longer) prior to starting the study (except for acetaminophen; birth control pills; implantable or injectable birth control; and estrogen, testosterone, and/or progesterone replacement in menopausal women)
  7. Unwilling to abstain from smoking for the duration of the study.
  8. Any clinically-significant, underlying abnormalities in rhythm, conduction, or morphology of the resting ECG that may interfere with the interpretation of QTc interval changes
  9. Positive result for the urine or serum human chorionic gonadotropin (hCG) test administered at screening (females with child bearing potential)
  10. A past medical history of clinically significant ECG abnormalities or a family history (grandparents, parents, or siblings) of either a long or a short QT syndrome
  11. Personal history of unexplained syncope.
  12. Women who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 acceptable methods of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier method(s) or male partner sterilization). Women ≥2 years postmenopausal or surgically sterile are exempt from this exclusion
  13. A history of hypersensitivity to moxifloxacin or any member of the quinolone class of antimicrobial agents
  14. Positive virology screen for human immunodeficiency virus (HIV) or hepatitis B or C virus (HBV or HCV, respectively)
  15. Participated in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
  16. Any condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01762839

Locations
United States, Wisconsin
Spaulding Clinical
West Bend, Wisconsin, United States, 53095
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Carlos Sanabria, MD Spaulding Clinical
  More Information

No publications provided

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT01762839     History of Changes
Other Study ID Numbers: MDCO-ORI-12-02
Study First Received: December 12, 2012
Last Updated: April 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014