Safety Study Designed to Study the Effects of Two Different Doses of CXA-101/Tazobactam, a Low Dose and a High Dose, on the QT/QTc Intervals in Healthy Subjects

NCT02508753 | Completed Phase 1 DMC

• 2 other identifiers: 7625A-033CXA-QT-10-02
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is look at the possible side effects of two different doses of CXA-101/tazobactam, a low dose and a high dose, on participant's heart.

Conditions

Healthy

Keywords

QT/QTc Intervals

Outcome Measures

Primary Outcomes (2)

• The change from the pre-dose baseline in the individual subject (subject-specific) correction, QTcI.

  The primary endpoint is the baseline-adjusted change in the QTcI between time-matched placebo and study drug.

  Baseline through Day 13

• The change from the periodic specific pre-dose baseline of QT/QTcI

  The primary endpoint is the change from the periodic specific pre-dose baseline of QT/QTcI corrected by QTcI across all dose groups

  Baseline through Day 13

Secondary Outcomes (3)

• The change from pre-dose baseline in the QT/QTcI corrected by QTcB and QTcF interval.

  Baseline through Day 13

• Characterize concentration-response relationship for QT/QTcI

  Baseline through Day 13

• Provide safety information by the collection of adverse events

  Baseline through Day 21

Study Arms (4)

CXA-101/tazobactam therapeutic dose

EXPERIMENTAL

Drug: CXA-101/tazobactam

CXA-101/tazobactam supra-therapeutic dose

EXPERIMENTAL

Drug: CXA-101/tazobactam

Moxifloxacin

ACTIVE COMPARATOR

Drug: Moxifloxacin

Placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

CXA-101/tazobactam DRUG

1000/500 mg single IV dose administered over 60 minutes

CXA-101/tazobactam therapeutic dose

Moxifloxacin DRUG

400 mg tablet

Moxifloxacin

placebo DRUG

single IV dose of a saline solution administered over 60 minutes plus oral over-encapsulated moxifloxacin placebo tablet administered at the start of infusion.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male and/or female, 18-45 years of age who can provide written Informed Consent.
• Body mass index (BMI) between 18-30, inclusive.
• Medically healthy with no clinically significant abnormal screening results (laboratory profiles, medical histories, ECGs, physical exam.
• Voluntarily consent to participate in the study.
• Normal blood pressure (\<140 mmHg systolic and \<90 mmHg diastolic).
• Normal 12-lead ECG, as defined as:
• Consistent sinus rhythm No clinically significant conduction disorders PR interval between 120 and 210 milliseconds (msec), inclusive Heart rate (HR) greater than or equal to 50 beats per minute (bpm) and less than or equal to 100 bpm QRS interval less than or equal to 110 msec QT intervals that can be consistently analyzed (T wave amplitude 2 mm or greater, lack of artifact \[noise\] and excessive baseline wandering, without any form of bundle branch block).
• QTcF interval less than or equal to 430 msec for males and less than or equal to 450 msec for females.
• Calculated creatinine clearance \>80 mL/min. at screening using the Cockcroft-Gault formula.
• If female, subject must have a negative serum pregnancy test at screening and agrees to either be sexually inactive (abstinent) for 14 days prior to screening and throughout the study, or use one of the following acceptable birth control methods:
• Intrauterine device (IUD) in place for at least 2 months prior to Day 1 and through study completion; or,
• Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through study completion; or
• Stable hormonal contraceptive (with the same medication, if possible) for at least 3 months prior to Day 1 through one month after completion of study; or
• Surgical sterilization (vasectomy) of partner at least 6 months prior to Day 1; or
• Naturally postmenopausal for a minimum of 2 consecutive years prior to Day 1; or

You may not qualify if:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
• History of additional risk factors for Torsade de Pointes (e.g., hypokalemia, family history of long QT Syndrome, family history of Short QT Syndrome, or family history of unexplainable early sudden death).
• History of invasive cancer within the past 5 years (excluding non-melanoma skin cancers).
• History of sensitivity or allergy to the quinolone class of antibiotics, cephalosporin class of antibiotics, or the beta-lactam class of antibiotics.
• History or presence of alcoholism or drug abuse within the past 2 years.
• History of hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV).
• History of clinically significant syncope.
• History of clinically significant psychiatric illness that would prevent the subject from providing a valid Informed Consent Form (ICF).
• Use of tobacco products within the previous 6 months.
• Donation of blood within 45 days prior to Study Day 1.
• Plasma donation within 30 days prior to Study Day 1.
• Participation in a study of an investigational drug within 30 days prior to the baseline ECG.
• Participation in another clinical trial within 30 days prior to the day of check-in for this study.
• Female and pregnant or lactating.
• Has angina, uncontrolled hypertension, clinically significant cardiac arrhythmias, or any other clinically significant cardiovascular abnormality.

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (1)

Cetero Reserach

Fargo, North Dakota, 58104, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: July 27, 2015
• Study Start: June 1, 2010
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: January 26, 2017

Record last verified: 2017-01

Locations

US (1)