Clinical trial NCT01762839: A Study to Assess the Cardiac Safety of Oritavancin in Healthy Participants
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-01-08
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study was to generate cardiac safety data using a supratherapeutic oritavancin dose of 1600 milligrams (mg).

Detailed description: This study was 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 QT corrected for pulse rate (QTc) intervals.

Eligibility 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, body mass index between 18 and 30 kilograms/meter squared.
3. In good health based upon results of medical history, physical examination, no clinically significant 12-lead electrocardiogram (ECG) results, and laboratory test results.
4. Serum magnesium and potassium levels within the normal range at Screening.
5. Agreed 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: participants who had histamine-like infusion reactions to a glycopeptide were not excluded.
2. A resting pulse rate \< 50 beats per minute (bpm) or \> 100 bpm.
3. Systolic blood pressure \< 90 millimeters of mercury (mmHg) or diastolic blood pressure \< 50 mmHg.
4. A QTc with the Fridericia correction \> 450 microseconds (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 medications or herbal preparations within 14 days or 5-times the elimination half-life (whichever was 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 have interfered with the interpretation of QTc interval changes.
9. Positive result for the urine or serum human chorionic gonadotropin test administered at Screening (females with childbearing 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 were pregnant or nursing, or who were of childbearing potential and unwilling to use at least 2 acceptable methods of birth control (for example, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier method(s) or male partner sterilization). Women ≥ 2 years postmenopausal or surgically sterile were 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 or hepatitis B or C virus, 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 participant at increased risk from participating in the study.

Primary outcomes:
measure: Placebo-adjusted change from Baseline in QTcF
timeFrame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time
Secondary outcomes:
measure: Placebo-adjusted change from baseline in QTcB, HR, RR, PR, and QRS interval analyses.
timeFrame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time
measure: Placebo adjusted change from Baseline in the appearance or worsening of ST, T and U-wave morphology.
timeFrame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time
measure: Effects on the QTc interval related to plasma concentration levels of oritavancin
timeFrame: predose, 3,3.5,4,5,6,7,9,11,15,24 hours post infusion start time
measure: Evaluate the number of volunteers with adverse events or abnormalities in lab/urine results and safety ECGs as measures of safety and tolerability
timeFrame: Day 0 through Day 7
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical
state: Wisconsin
Study officials:
affiliation: Spaulding Clinical
name: Carlos Sanabria, MD
role: PRINCIPAL_INVESTIGATOR
References: