Normal Healthy SubjectsPhase 1NCT01941446
A Thorough QT/QTc Study to Evaluate the Effects of an Intravenous Infusion of Eravacycline (TP-434) on Cardiac Repolarization
A Phase 1 study of Normal Healthy Subjects, run by Tetraphase Pharmaceuticals, Inc.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Healthy Subjects
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- No sites listed yet
- Study dates
- Mar 2013to Jul 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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;
- History of alcoholism or drug abuse within 2 years prior to dosing;
- Typical weekly alcohol consumption of 14 alcoholic drinks. One drink is defined as 1 glass of beer (approximately 10 oz to 12 oz) or 1 can (12 oz) of beer, 1 glass of wine (approximately 4 oz to 5 oz), or 1 glass of distilled spirits (hard liquor) containing 1 oz of the liquor (1 oz of liquid is approximately 30 mL);
- Alcohol consumption within 48 hours prior to dosing;
- Use of tobacco, nicotine, or nicotine-replacement products within the 3 months prior to the first dose of study drug through the last study visit;
- Unwillingness to refrain from caffeine and other xanthine-containing beverages, including coffee and tea, as well as grapefruit juice, Seville oranges, or chocolate within 24 hours prior to and after dosing;
- History of human immunodeficiency virus (HIV) or hepatitis C virus or a positive test at screening for HIV antibody, hepatitis C antibody, or hepatitis B surface antigen;
- Cumulative blood donation of >500 mL within 2 months prior to the Screening Visit;
- Use of any prescription or non-prescription medication, including vitamins or herbal medications, within 7 days, or 5 half-lives (if known), whichever is longer, prior to dosing in any of the 3 periods and within 24 hours after dosing in any period. The use of acetaminophen, naproxen, and ibuprofen is permitted except for within 24 hours prior to dosing;
- Use of any prescription or non-prescription medication that may cause QT prolongation within 14 days, or 5 half lives, whichever is longer, prior to dosing in Period 1 through 24 hours following dosing in Period 3;
- Any known exposure to prescription or non prescription medications or other substances, such as paint solvents or pesticides, known to induce or inhibit drug metabolizing enzymes or transport system enzymes, within 30 days or 5 half-lives, whichever is longer, prior to dosing in Period 1 through 24 hours following dosing in Period 3, with the exception of hormonal contraception;
- Unwillingness to abstain from strenuous exercise (e.g., heavy lifting, weight training, calisthenics, aerobics) for at least 48 hours prior to admission to the investigational site;
- Investigational site personnel directly affiliated with this study;
- Poor mental function or any other reason to expect subject difficulty in complying with the requirements of the study in the judgment of the Investigator; or
- Failure to comply with protocol requirements or whose further participation in the study would be unsuitable to the subject, as determined by the Investigator.
About this study
Official title: A Randomized, Placebo- and Positive Controlled, Three-Way, Crossover Study to Evaluate the Effects of an Intravenous Infusion of Eravacycline (TP-434) on Cardiac Repolarization in Healthy Male and Female Subjects: A Thorough QT/QTc Study
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.
Read the detailed description
Each of the following treatments will be evaluated on Day 1 of each period in a crossover fashion. The IV eravacycline (TP-434) and IV placebo will be double-blinded.
- Treatment A: Eravacycline (TP-434) 1.5 mg/kg administered intravenously over 60 minutes and one placebo oral tablet;
- Treatment B: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one moxifloxacin 400 mg oral tablet; and
- Treatment C: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one placebo oral tablet.
Subjects will be randomized to a treatment sequence according to a pre-generated treatment scheme. Subjects will receive a different treatment during each of the 3 periods.
- Conditions
- Normal Healthy Subjects
- Being tested
- Eravacyline, Moxifloxacin, and placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eravacyline, Moxifloxacin, and placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| pre-generated treatment scheme | Experimental | Treatment A: Eravacycline (TP-434) 1.5 mg/kg administered intravenously over 60 minutes and one placebo oral tablet Receives: 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 Receives: 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 Receives: Drug: Eravacyline, Moxifloxacin, and placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 11 weeks
Secondary outcomes (1)
Evaluate the effect of eravacycline (TP-434) on cardiac repolarization
- To evaluate the effect of eravacycline (TP-434) on cardiac repolarization compared with placebo by calculating the differences between the time-matched mean changes from baseline of QTcB (ΔΔQTcB) and QTcF (ΔΔQTcF) in healthy male and female subjects;
- To evaluate the correlation between the differences in time-matched baseline-adjusted mean changes of QTc in eravacycline (TP-434) and placebo (ΔΔQTcI, ΔΔQTcB, and ΔΔQTcF) and plasma concentrations of eravacycline (TP-434), TP-498, and TP-6208;
- To evaluate the correlation between QTcI, QTcB, and QTcF changes from baseline (ΔQTcI, ΔQTcB, and ΔQTcF) and plasma concentrations of eravacycline (TP-434), TP 498, and TP-6208; and
- To evaluate assay sensitivity by measuring the effect of moxifloxacin on QTc compared to placebo (ΔΔQTcI).
Measured: 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2013 (estimated)
- Study startMar 2013
- Primary completionJun 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal Healthy SubjectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tetraphase Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrick T Horn, MD, PhD, Study director, Tetraphase Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01941446
- Sponsor's protocol ID
- TP-434-004
- Status last verified
- Dec 2021
- First submitted
- 10 Sep 2013
- Last updated
- 27 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo- and Positive Controlled, Three-Way, Crossover Study to Evaluate the Effects of an Intravenous Infusion of Eravacycline (TP-434) on Cardiac Repolarization in Healthy Male and Female Subjects: A Thorough QT/QTc Study
- ClinicalTrials.gov ID
- NCT01941446
- Acronym / sponsor ID
- TP-434-004
- Conditions
- Normal Healthy Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Tetraphase Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- Mar 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 13 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Each of the following treatments will be evaluated on Day 1 of each period in a crossover fashion. The IV eravacycline (TP-434) and IV placebo will be double-blinded.
- Treatment A: Eravacycline (TP-434) 1.5 mg/kg administered intravenously over 60 minutes and one placebo oral tablet;
- Treatment B: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one moxifloxacin 400 mg oral tablet; and
- Treatment C: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one placebo oral tablet.
Subjects will be randomized to a treatment sequence according to a pre-generated treatment scheme. Subjects will receive a different treatment during each of the 3 periods.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| pre-generated treatment scheme | Experimental | Drug: Eravacyline, Moxifloxacin, and placeboTreatment A: Eravacycline (TP-434) 1.5 mg/kg administered intravenously over 60 minutes and one placebo oral tablet |
| Pre-generated tratment scheme | Placebo comparator | Drug: Eravacyline, Moxifloxacin, and placeboTreatment B: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one moxifloxacin 400 mg oral tablet |
| Moxifloxacin | Placebo comparator | Drug: Eravacyline, Moxifloxacin, and placeboTreatment C: Placebo (0.9% sodium chloride) administered intravenously over 60 minutes and one placebo oral tablet |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (29 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eravacyline, Moxifloxacin, and placebo | Drug | Moxifloxacin, Pre-generated tratment scheme, pre-generated treatment scheme |
Primary outcome
Evaluate the effect of a therapeutic dose of an IV infusion of eravacycline (TP-434) on cardiac repolarization compared to placebo
Time frame: 11 weeks
Calculating the differences between time-matched mean change from baseline of QTcI (ΔΔQTcI = ΔQTcI[TP-434]-ΔQTcI[placebo]) in healthy male and female subjects.
1 secondary outcome
Evaluate the effect of eravacycline (TP-434) on cardiac repolarization
Time frame: 11 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick T Horn, MD, PhD study director
Tetraphase Pharmaceuticals, Inc
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Normal Healthy Subjects, run by Tetraphase Pharmaceuticals, Inc.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the effect of a therapeutic dose of an IV infusion of eravacycline (TP-434) on cardiac repolarization compared to placebo (time frame: 11 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2021.