HealthyPhase 1NCT03564158
Evaluate Effects of Meropenem-Vaborbactam on QT/QTc in Healthy Volunteers
A Phase 1 study testing meropenem-vaborbactam and Moxifloxacin in people with Healthy, run by Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.) at 1 site in United States.
Trial summary
This Thorough-QT (TQT) study in healthy volunteers will be conducted in two phases. Phase One will be used to identify a safe supratherapeutic dose to be used in the TQT study (Phase Two). Phase Two will be a 4-way crossover TQT study. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- meropenem-vaborbactam and Moxifloxacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 19 Nov 2018
- 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
- Male or female subject between 18 and 55 years of age, inclusive, with a body mass index (BMI) ≥18 to ≤33 kilogram (kg)/m2.
- All women of child-bearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose. Accepted methods of contraception include: mechanical products (e.g., intrauterine device) or double-barrier methods (e.g., diaphragm, condoms, cervical cap) with spermicide or hormonal contraceptives (i.e., oral, implanted or injectable contraceptive hormones) or abstinence. Oral contraceptives must be used together with a second method of birth control. If the female subject has a male partner who has had a vasectomy, one additional form of medically acceptable contraception (condom or spermicide) must also be used. The subject's understanding of this requirement must be documented by the Investigator.
- Males with female partners of childbearing potential must agree to use a highly effective, medically acceptable form of contraception from the Screening period through 30 days after the last dose. Males with female partners of childbearing potential who themselves are surgically sterile (status post vasectomy) must agree to use condoms with spermicide over the same period of time. Male subjects must agree to practice the above birth control methods for 30 days after the final dose. Males must agree to not donate sperm through 30 days after the final dose.
- Stable health based on no clinically-significant findings on the medical history, physical examination, or clinical laboratory test results at screening and prior to study drug administration (as determined and documented by the Investigator).
- Willing to comply with all study activities and procedures and provides written informed consent prior to any study procedures
Who cannot join
- Known hypersensitivity to beta-lactam antibiotics (including meropenem), fluoroquinolone antibiotics (including moxifloxacin) or vaborbactam.
- An uninterpretable or abnormal screening electrocardiogram (ECG) indicating a second or third degree atrioventricular block, or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant or one or more of the following: QRS interval >110 milliseconds (ms); QTcF >430 ms (males) and >450 ms (females); PR interval >200 ms; heart rate (HR) <50 beats per minutes (bpm); or >90 bpm.
- History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina. Subjects will also be excluded if there is a family history of long QT syndrome or Brugada syndrome or unexplained sudden death.
- Subject has any clinically relevant abnormalities, as determined by the Investigator, in the laboratory results at Screening or admission of each study period
- Serum potassium, serum magnesium, or albumin-corrected calcium lower than the lower limit of normal for the reference lab at Screening or admission of each study period. Calcium will be corrected for albumin using the formula: Corrected Calcium = (0.8 * (Normal Albumin - Pt's Albumin)) + Serum Ca where Normal Albumin is 4.0 g/dL.
- Hemoglobin and hematocrit lower than the lower limit of normal for the reference lab at Screening.
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- Subject has an abnormal liver function tests: alanine aminotransferase [ALT], aspartate aminotransferase [AST], or bilirubin greater than 1.2X the upper limits of normal at Screening.
- History of central nervous system (CNS) disorder including convulsions.
- A sustained supine systolic blood pressure >140 mmHg or <90 mmHg or a supine diastolic blood pressure >90 mmHg or <50 mmHg at Screening or Check in (Day -1). Blood pressure may be retested once in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits after 2 assessments, in which case the subject should not be randomized.
- Impaired renal function as evidenced by estimated glomerular filtration rate (eGFR) <50.
- Unstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia.
- History of acquired immunodeficiency syndrome or history of a positive test result for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or hepatitis B surface antigen (HBsAg) at Screening.
- Positive drug, alcohol, or tobacco screen.
- Clinically-significant illness, including viral syndromes within 3 weeks of dosing.
- Women who are pregnant (or planning to become pregnant within the next 6 months) or currently breastfeeding. A negative serum pregnancy test is required before enrolling in the study.
- Participation in another investigational drug or device study or treated with an investigational drug within 30 days or 5 half lives, whichever is longer, before dosing. Any subject who participated in Phase One of this trial is not eligible to participate in Phase Two.
- Consumed more than 28 units of ethanol per week at any time in the 6 months before dosing (1 unit of ethanol is equivalent to 8 ounces of beer, 4 ounces of wine, or 1 ounce of spirits) or history of alcoholism and/or drug/chemical abuse.
- Use of prescription medications (with the exception of oral contraceptives and hormone replacement therapy), including nonsteroidal anti-inflammatory drugs or sucralfate and medications known to prolong the QT/QTc interval or natural health products/herbal preparations within 14 days or 5 half lives (whichever is longer) before study drug dosing, or use of an over-the-counter (OTC) medication (excluding acetaminophen), vitamins, or supplements (including omega-3 fish oils) within 7 days before study drug dosing.
- Use of alcohol , caffeine , or xanthine containing products, Seville oranges (sour), grapefruit, or grapefruit juice, within 72 hours before study drug dosing.
- Current use or has used tobacco- or nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, etc.) 30 days before study drug dosing.
- Strenuous activity (e.g., sports) from 96 hours (4 days) prior to entry into the clinical research unit and throughout the study (until the final follow-up call is conducted).
- Donated more than 500 milliliter (mL) of blood or significant blood loss within 60 days prior to signing the informed consent form.
- Any other medical, psychological, or social condition that, in the opinion of the principal investigator or the medical monitor, would prevent the subject from fully participating in the study, would represent a concern for study compliance, or would constitute a safety concern to the subject.
- An employee of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as a family member of the employee or investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Placebo- and Positive-Controlled, Crossover Study to Evaluate the Effect of Meropenem-Vaborbactam on the QT/QTc Interval in Healthy Volunteers
This Thorough-QT (TQT) study in healthy volunteers will be conducted in two phases. Phase One will be used to identify a safe supratherapeutic dose to be used in the TQT study (Phase Two). Phase Two will be a 4-way crossover TQT study. Thirty-two subjects will receive all 4 of the following treatments in randomized sequence.
- meropenem-vaborbactam 4 g (meropenem 2 g- vaborbactam 2 g) therapeutic dose infused intravenously over 3 hours
- meropenem-vaborbactam supratherapeutic dose to be determined infused intravenously over 3 hours.
- Placebo (normal saline) to match meropenem-vaborbactam volume infusion over 3 hours
- Moxifloxacin 400 mg positive control (oral; open-label)
Read the detailed description
This Thorough-QT (TQT) study in healthy volunteers will be conducted in two phases. Phase One (n=15) will be used to identify a safe supratherapeutic dose to be used in the TQT study (Phase Two). Phase Two will be a randomized, placebo and positive-controlled, 4-way crossover TQT study. Thirty-two subjects will receive all 4 of the following treatments in randomized sequence.
- meropenem-vaborbactam 4 g (meropenem 2 g- vaborbactam 2 g) therapeutic dose infused intravenously over 3 hours
- meropenem-vaborbactam supratherapeutic dose to be determined infused intravenously over 3 hours.
- Placebo (normal saline) to match meropenem-vaborbactam volume infusion over 3 hours
- Moxifloxacin 400 mg positive control (oral; open-label)
- Conditions
- Healthy
- Being tested
- meropenem-vaborbactam, Placebo, Moxifloxacin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
meropenem-vaborbactamDrug
Also called Vabomere
Meropenem-Vaborbactam being studied for effects on TQT
PlaceboDrug
Also called Saline
Placebo
MoxifloxacinDrug
Also called Moxi
Active Comparator
| Study group | Role | What they receive |
|---|---|---|
| meropenem 2 g- vaborbactam 2 g | Experimental | Approved Dose Receives: Drug: meropenem-vaborbactam |
| meropenem-vaborbactam (dose TBD) | Experimental | Supratherapeutic Dose Receives: Drug: meropenem-vaborbactam |
| Moxifloxacin 400 mg | Active comparator | Active Control Receives: Drug: Moxifloxacin |
| Normal Saline (placebo) | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Change in placebo corrected QTcF after dosing
Measured: 24 hours after start of dosing
Secondary outcomes (6)
Change-from-baseline HR
Change in HR after dosing
Measured: 24 hours after start of dosing
Change-from-baseline QTcF inteval
Change in QTcF after dosing
Measured: 24 hours after start of dosing
Change-from-baseline PR interval
Change in PR after dosing
Measured: 24 hours after start of dosing
Change-from-baseline QRS interval
Change in QRS after dosing
Measured: 24 hours after start of dosing
Change-from-baseline RR interval
Change in RR after dosing
Measured: 24 hours after start of dosing
Change-from-baseline QT interval
Change in QT interval after dosing
Measured: 24 hours after start of dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2018
- Study start1 May 2018
- Primary completion19 Nov 2018
- Study completion19 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biomedical Advanced Research and Development Authority
- Responsible party
- Sponsor
- Investigators
- Sue Cammarata, Study director, Melinta Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03564158
- Sponsor's protocol ID
- Rempex 512
- Status last verified
- Jan 2019
- First submitted
- 30 Apr 2018
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo- and Positive-Controlled, Crossover Study to Evaluate the Effect of Meropenem-Vaborbactam on the QT/QTc Interval in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03564158
- Acronym / sponsor ID
- Rempex 512
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)Industry (pharma, biotech, devices)
- Collaborators
- Biomedical Advanced Research and Development Authority
- Study start
- 1 May 2018 (actual)
- Primary completion
- 19 Nov 2018 (actual)
- Study completion
- 19 Nov 2018 (actual)
- First posted
- 20 Jun 2018 (actual)
- 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 Thorough-QT (TQT) study in healthy volunteers will be conducted in two phases. Phase One will be used to identify a safe supratherapeutic dose to be used in the TQT study (Phase Two). Phase Two will be a 4-way crossover TQT study. Thirty-two subjects will receive all 4 of the following treatments in randomized sequence.
- meropenem-vaborbactam 4 g (meropenem 2 g- vaborbactam 2 g) therapeutic dose infused intravenously over 3 hours
- meropenem-vaborbactam supratherapeutic dose to be determined infused intravenously over 3 hours.
- Placebo (normal saline) to match meropenem-vaborbactam volume infusion over 3 hours
- Moxifloxacin 400 mg positive control (oral; open-label)
Detailed description
This Thorough-QT (TQT) study in healthy volunteers will be conducted in two phases. Phase One (n=15) will be used to identify a safe supratherapeutic dose to be used in the TQT study (Phase Two). Phase Two will be a randomized, placebo and positive-controlled, 4-way crossover TQT study. Thirty-two subjects will receive all 4 of the following treatments in randomized sequence.
- meropenem-vaborbactam 4 g (meropenem 2 g- vaborbactam 2 g) therapeutic dose infused intravenously over 3 hours
- meropenem-vaborbactam supratherapeutic dose to be determined infused intravenously over 3 hours.
- Placebo (normal saline) to match meropenem-vaborbactam volume infusion over 3 hours
- Moxifloxacin 400 mg positive control (oral; open-label)
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| meropenem 2 g- vaborbactam 2 g | Experimental | Drug: meropenem-vaborbactamApproved Dose |
| meropenem-vaborbactam (dose TBD) | Experimental | Drug: meropenem-vaborbactamSupratherapeutic Dose |
| Moxifloxacin 400 mg | Active comparator | Drug: MoxifloxacinActive Control |
| Normal Saline (placebo) | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male or female subject between 18 and 55 years of age, inclusive, with a body mass index (BMI) ≥18 to ≤33 kilogram (kg)/m2.
- All women of child-bearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose. Accepted methods of contraception include: mechanical products (e.g., intrauterine device) or double-barrier methods (e.g., diaphragm, condoms, cervical cap) with spermicide or hormonal contraceptives (i.e., oral, implanted or injectable contraceptive hormones) or abstinence. Oral contraceptives must be used together with a second method of birth control. If the female subject has a male partner who has had a vasectomy, one additional form of medically acceptable contraception (condom or spermicide) must also be used. The subject's understanding of this requirement must be documented by the Investigator.
- Males with female partners of childbearing potential must agree to use a highly effective, medically acceptable form of contraception from the Screening period through 30 days after the last dose. Males with female partners of childbearing potential who themselves are surgically sterile (status post vasectomy) must agree to use condoms with spermicide over the same period of time. Male subjects must agree to practice the above birth control methods for 30 days after the final dose. Males must agree to not donate sperm through 30 days after the final dose.
- Stable health based on no clinically-significant findings on the medical history, physical examination, or clinical laboratory test results at screening and prior to study drug administration (as determined and documented by the Investigator).
- Willing to comply with all study activities and procedures and provides written informed consent prior to any study procedures
Key exclusion criteria (24 listed)
- Known hypersensitivity to beta-lactam antibiotics (including meropenem), fluoroquinolone antibiotics (including moxifloxacin) or vaborbactam.
- An uninterpretable or abnormal screening electrocardiogram (ECG) indicating a second or third degree atrioventricular block, or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant or one or more of the following: QRS interval >110 milliseconds (ms); QTcF >430 ms (males) and >450 ms (females); PR interval >200 ms; heart rate (HR) <50 beats per minutes (bpm); or >90 bpm.
- History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina. Subjects will also be excluded if there is a family history of long QT syndrome or Brugada syndrome or unexplained sudden death.
- Subject has any clinically relevant abnormalities, as determined by the Investigator, in the laboratory results at Screening or admission of each study period
- Serum potassium, serum magnesium, or albumin-corrected calcium lower than the lower limit of normal for the reference lab at Screening or admission of each study period. Calcium will be corrected for albumin using the formula: Corrected Calcium = (0.8 * (Normal Albumin - Pt's Albumin)) + Serum Ca where Normal Albumin is 4.0 g/dL.
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 |
|---|---|---|
| meropenem-vaborbactamAlso: VabomereMeropenem-Vaborbactam being studied for effects on TQT | Drug | meropenem 2 g- vaborbactam 2 g, meropenem-vaborbactam (dose TBD) |
| PlaceboAlso: SalinePlacebo | Drug | Normal Saline (placebo) |
| MoxifloxacinAlso: MoxiActive Comparator | Drug | Moxifloxacin 400 mg |
Primary outcome
Placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF)
Time frame: 24 hours after start of dosing
Change in placebo corrected QTcF after dosing
6 secondary outcomes
Change-from-baseline HR
Time frame: 24 hours after start of dosing
Change-from-baseline QTcF inteval
Time frame: 24 hours after start of dosing
Change-from-baseline PR interval
Time frame: 24 hours after start of dosing
Change-from-baseline QRS interval
Time frame: 24 hours after start of dosing
Change-from-baseline RR interval
Time frame: 24 hours after start of dosing
Change-from-baseline QT interval
Time frame: 24 hours after start of dosing
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 10 Jan 2019.
- Individual participant dataSharing planned: No
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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.
Sue Cammarata study director
Melinta Therapeutics, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing meropenem-vaborbactam and Moxifloxacin in people with Healthy, run by Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.) at 1 site in United States.
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 5 inclusion and 24 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 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Placebo-corrected change-from-baseline QTcF interval (ΔΔQTcF) (time frame: 24 hours after start of dosing). 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 10 Jan 2019.