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

• ClinicalTrials.gov Identifier: NCT01762839
• Recruitment Status: Completed
• First Posted: January 8, 2013
• Last Update Posted: April 17, 2013
• Sponsor: The Medicines Company
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Single-Dose IV Oritavancin Diphosphate; Drug: Placebo; Drug: Moxifloxacin	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: January 2013
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
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.
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   Placebo-adjusted change from baseline in QTcF (QTc with the Fridericia correction) between each treatment and placebo.

Secondary Outcome Measures :

1. 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 ]
   Placebo-adjusted change from baseline in QTcB, HR, RR, PR, and QRS interval analyses.
2. 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 ]
   Placebo adjusted change from baseline in the appearance or worsening of ST, T and U-wave morphology.
3. 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 ]
   Compare the effects on the QTc interval to the plasma levels of oritavancin using concentration-effect modeling
4. 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 ]
   Compare safety and tolerability in healthy volunteers after a single IV dose of 1600 mg oritavancin

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT01762839
• Other Study ID Numbers: MDCO-ORI-12-02
• First Posted: January 8, 2013
• Last Update Posted: April 17, 2013
• Last Verified: April 2013

Additional relevant MeSH terms:

Moxifloxacin; Oritavancin; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents