A Thorough QT/QTc Study to Evaluate the Effects of an Intravenous Infusion of Eravacycline (TP-434) on Cardiac Repolarization

NCT01941446 | Completed Phase 1

• 1 other identifier: TP-434-004
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, placebo- and positive-controlled (moxifloxacin), 3-period, 3-way crossover thorough QT study, which includes a Screening Period, Treatment Periods (1 through 3), and a Follow-up Visit. Subjects will be confined to the investigational site for 4 nights/3 days during Period 1 and for 3 nights/2 days during Periods 2 and 3. There will be a minimum of a 14 day washout between treatments.

Conditions

Normal Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• Evaluate the effect of a therapeutic dose of an IV infusion of eravacycline (TP-434) on cardiac repolarization compared to placebo

  Calculating the differences between time-matched mean change from baseline of QTcI (ΔΔQTcI = ΔQTcI\[TP-434\]-ΔQTcI\[placebo\]) in healthy male and female subjects.

  11 weeks

Secondary Outcomes (1)

• Evaluate the effect of eravacycline (TP-434) on cardiac repolarization

  11 weeks

Study Arms (3)

pre-generated treatment scheme

EXPERIMENTAL

Treatment A: Eravacycline (TP-434) 1.5 mg/kg administered intravenously over 60 minutes and one placebo oral tablet

Drug: Eravacyline, Moxifloxacin, and placebo

Pre-generated tratment scheme

PLACEBO COMPARATOR

Treatment B: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one moxifloxacin 400 mg oral tablet

Drug: Eravacyline, Moxifloxacin, and placebo

Moxifloxacin

PLACEBO COMPARATOR

Treatment C: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one placebo oral tablet

Drug: Eravacyline, Moxifloxacin, and placebo

Interventions

Eravacyline, Moxifloxacin, and placebo DRUG

Moxifloxacin; Pre-generated tratment scheme; pre-generated treatment scheme

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects of 18 to 55 years of age;
• Females must be surgically sterile (hysterectomy and/or bilateral oophorectomy), post-menopausal for 1 year (with follicle-stimulating hormone \[FSH\] in menopausal range), or agree to use 2 medically accepted, effective methods of birth control (e.g., hormonal contraception, including oral, implant/patch, or injection, or latex condom with spermicide, diaphragm with intravaginal spermicide, cervical cap with spermicide, or indwelling intrauterine device) from the time of signing informed consent until 2 weeks after the Follow-Up Visit. One of the birth control methods must be a barrier method;
• Male subjects with sexual partners of childbearing potential must agree to use 2 medically accepted, effective methods of birth control (e.g., hormonal contraception, including oral, implant/patch, or injection, or latex condom with spermicide, diaphragm with intravaginal spermicide, cervical cap with spermicide, or indwelling intrauterine device) for the duration of the study and for 90 days after the Follow-up Visit. Male subjects who have had a vasectomy \>6 months prior to the first dose of study drug must agree to use 1 medically accepted barrier method for the duration of the study and for 90 days after the Follow-up Visit;
• Male subjects (including those who have had vasectomies \>6 months prior to the first dose of study drug) whose partners are currently pregnant must agree to use a barrier method (without spermicide) for the duration of the study and for 2 weeks after the Follow-up Visit;
• Body mass index of 18 kg/m2 to 33 kg/m2, inclusive;
• Non-smokers must have quit smoking \>3 months prior to the Screening Visit;
• Have negative alcohol and drug screens;
• Have a quantitative urine cotinine screen \<3;
• Willing and able to be confined to the investigational site as required by the protocol; and
• Able to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines.

You may not qualify if:

• Evidence of clinically significant hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal, hepatic, psychiatric, neurologic, or allergic disease (including multiple or clinically significant drug allergies), cancer, or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, interfere with the integrity of electrophysiologic data, or place the subject at an unacceptable risk as a participant in this study;
• A personal or family history of long QT syndrome, Torsades de pointes, or other complex ventricular arrhythmias or family history of sudden death;
• Mean QTcF interval \>450 msec on screening ECG, performed in triplicate. The mean QTcF of these tracings will be used by the Investigator;
• Cardiac conduction abnormalities denoted by any of the following at the Screening Visit: evidence of second-degree (Mobitz type II) or third-degree atrioventricular block, evidence of ventricular pre-excitation, complete left bundle branch block, right bundle branch block, intraventricular conduction delay with QRS duration \>120 msec, atrial fibrillation, or presence of cardiac pacemaker; PR interval \>220 msec or \<120 msec; heart rate \<45 bpm or \>90 bpm; other clinically-significant ECG abnormalities (measured as a mean value from triplicate ECGs);
• Use of hormone replacement therapy;
• Any major surgical procedure within 3 months prior to the first dose of study drug;
• Gastrointestinal disorders or surgical procedures that could interfere significantly with the absorption of orally administered drugs;
• Use of another investigational drug or device within 30 days prior to receiving eravacycline (TP-434), or within at least 5 half-lives of the previous investigational drug, whichever is longer;
• History of malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer);
• History or presence of hypertension (defined as systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg). If the subject's blood pressure is outside of the acceptable range at the Screening Visit, the subject may be retested within 24 hours at the discretion of the Investigator;
• Known allergies to moxifloxacin, other quinolone or tetracycline antibiotics, or related compounds or a history of multiple adverse drug allergies of any origin;
• Inadequate venous access;
• Obvious clinical signs or symptoms of liver disease, acute or chronic active hepatitis, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 the upper limit of normal (ULN). An abnormal ALT or AST test may not be repeated;
• Total bilirubin \>1.5 ULN with elevated direct bilirubin. An abnormal total or direct bilirubin test may not be repeated;
• Serum potassium, magnesium, or calcium levels that are outside of the laboratory's reference range;

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Patrick T Horn, MD, PhD

  Tetraphase Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 13, 2013
• Study Start: March 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 27, 2021

Record last verified: 2021-12