Cardiac Repolarization in Healthy SubjectsPhase 1NCT03709927
4-way Crossover QT Evaluation in Healthy Subjects
A Phase 1 study testing ZTI-01 and Moxifloxacin 400mg in people with Cardiac Repolarization in Healthy Subjects, run by Nabriva Therapeutics AG at 1 site in United States.
Trial summary
The purpose of this study is to evaluate if ZTI-01 (fosfomycin for injection), an investigational drug being developed to treat people with complicated urinary tract and kidney infections, has any effect on the electrical activity of the heart. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiac Repolarization in Healthy Subjects
- What is being tested?
- ZTI-01 and Moxifloxacin 400mg
- 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
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2018to 21 Aug 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
- physically and mentally healthy volunteer
- a man or woman, 18 to 55 years of age
- a woman of childbearing potential using birth control / negative pregnancy test or a woman of non-childbearing potential
- males with female partners of childbearing potential agree to use contraception
- body mass index 19.0 to 32.0 kg/m2; weight of at least 60.0 kg at Screening
- willing to complete the required 4 study periods
Who cannot join
- History or evidence of cerebrovascular or cardiac disease
- Uncontrolled hypertension
- Electrographically significant abnormalities on ECG
- Clinically significant medical history (PI assessment)
- Clinically relevant lab abnormalities (PI assessment)
- Calculated eGFR < 60.0 mL/min/1.73m2 based on CKD-EPI 2009 equation
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- Abnormal liver tests
- Positive serology HIV, HBsAg, or Hep C virus
- Hemoglobin, hematocrit, electrolytes below lower limit of normal
- Received any hepatic or renal clearance altering agents within 30 days
- History of allergy or hypersensitivity to drugs with clinically significant reaction
- Unwilling to refrain from strenuous exercise from 7 days prior to admission until discharge
- Uses any prescription drug / OTC, within 7 days prior to admission, or 14 days prior to Admission if the drug is a potential inducer or inhibitor of cP450, or 5 half-lives (if longer), or subject continued use of a prescription drug / OTC medication (except contraceptives)
- Scheduled to have surgical procedure during study
- Acute illness that has resolved in less than 14 days, or has had a major illness, or hospitalization within 1 month
- Unwilling to abstain from ingestion of caffeine or xanthine-containing products 96 hours prior and throughout study
- Unwilling to abstain from alcohol beginning 72 hours prior and throughout study
- History of high alcohol consumption within 6 months
- History of drug abuse (in the previous 3 years) or positive urine drug screen
- Used tobacco-containing products within 6 months or has a positive cotinine
- Consumed grapefruit and/or grapefruit juice within 14 days and throughout study
- Consumed other fruit juices within 72 hours and throughout study
- Consumed cruciferous vegetables or charbroiled meats within 7 days and throughout study
- Donated plasma or blood within 30 days or has a history of blood donation of > 450 mL within 3 months
- Used any investigational drug within 30 days
- Previously received fosfomycin
- Deemed by the Investigator to be inappropriate for this study
- Participated in another clinical study within 30 days (or 5 half-lives)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Blinded, Placebo and Moxifloxacin Controlled, 4-Period Crossover, Study Evaluating the Effect of ZTI-01 on 12-Lead Electrocardiogram Parameters in Healthy Adult Subject
The purpose of this study is to evaluate if ZTI-01 (fosfomycin for injection), an investigational drug being developed to treat people with complicated urinary tract and kidney infections, has any effect on the electrical activity of the heart.
Read the detailed description
This is a single-center, randomized, placebo-controlled, four-period, cross-over study to assess the effect of single-doses of ZTI-01 at therapeutic (T) and supratherapeutic (ST) plasma concentrations on the QTc interval versus placebo (P) and an open-label moxifloxacin (M) control (400 mg PO).
Assessment of safety data will include changes from baseline in vital signs and laboratory parameters, infusion site reactions, adverse events and clinically significant changes from baseline in 12-lead ECG parameters.
- Being tested
- ZTI-01, Moxifloxacin 400mg, Placebo IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZTI-01Drug
Also called IV fosfomycin, fosfomycin disodium, fosfomycin for injection
6g IV fosfomycin
Moxifloxacin 400mgDrug
Also called Positive control
oral moxifloxacin (Avelox 400 mg) + IV normal saline (Placebo)
Placebo IVOther
Also called Negative Control
IV Placebo (0.9% Normal Saline)
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic ZTI-01 6 g IV | Experimental | intravenous fosfomycin (only antibiotic in phosphonic acid derivative class) 6g Receives: Drug: ZTI-01 |
| Supra-therapeutic ZTI-01 12 g IV | Experimental | intravenous fosfomycin (only antibiotic in phosphonic acid derivative class) 12g Receives: Drug: ZTI-01 |
| moxifloxacin 400 mg PO | Active comparator | oral moxifloxacin 400mg film coated tablets - Avelox(TM) Receives: Drug: Moxifloxacin 400mg; Other: Placebo IV |
| Placebo IV | Placebo comparator | IV 0.9% normal saline solution Receives: Other: Placebo IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of ZTI-01 at the therapeutic and supra-therapeutic plasma concentration on cardiac repolarization expressed by QT interval
Determine the change-from-baseline QTc (ΔQTc) when compared with placebo, and moxifloxacin (400 mg PO)
Measured: 24 hour Holter ECG at Baseline (Day -1) & day of dosing (Day 1) in each of 4 periods. 10 replicates per time point at 13 timepoints: pre-dose: 60, 45 and 30 minutes; after the start of infusion: 0.5, 1 (end infusion), 1.25, 1.5, 2, 3, 4, 8, 12, & 24 hrs
Secondary outcomes (1)
Treatment emergent adverse events (TEAEs)
Number and percentage of subjects reporting a TEAE overall and by treatment
Measured: From Day 1 start of dosing up to Day 36-38 (final follow up visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2018
- Study start11 Jan 2018
- Primary completion12 Apr 2018
- Study completion21 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac Repolarization in 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
- Model description
- 4-way cross over (two doses of ZTI-01, placebo and oral moxifloxacin)
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nabriva Therapeutics AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Evelyn J Ellis-Grosse, PhD, Study chair, Chief Scientific Officer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03709927
- Sponsor's protocol ID
- ZTI-01-101
- Status last verified
- Mar 2019
- First submitted
- 8 May 2018
- Last updated
- 6 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: final report, publication
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Blinded, Placebo and Moxifloxacin Controlled, 4-Period Crossover, Study Evaluating the Effect of ZTI-01 on 12-Lead Electrocardiogram Parameters in Healthy Adult Subject
- ClinicalTrials.gov ID
- NCT03709927
- Acronym / sponsor ID
- ZTI-01-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Nabriva Therapeutics AGIndustry (pharma, biotech, devices)
- Study start
- 11 Jan 2018 (actual)
- Primary completion
- 12 Apr 2018 (actual)
- Study completion
- 21 Aug 2018 (actual)
- First posted
- 17 Oct 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.
The purpose of this study is to evaluate if ZTI-01 (fosfomycin for injection), an investigational drug being developed to treat people with complicated urinary tract and kidney infections, has any effect on the electrical activity of the heart.
Detailed description
This is a single-center, randomized, placebo-controlled, four-period, cross-over study to assess the effect of single-doses of ZTI-01 at therapeutic (T) and supratherapeutic (ST) plasma concentrations on the QTc interval versus placebo (P) and an open-label moxifloxacin (M) control (400 mg PO).
Assessment of safety data will include changes from baseline in vital signs and laboratory parameters, infusion site reactions, adverse events and clinically significant changes from baseline in 12-lead ECG parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 4-way cross over (two doses of ZTI-01, placebo and oral moxifloxacin)
| Arm | Type | Receives |
|---|---|---|
| Therapeutic ZTI-01 6 g IV | Experimental | Drug: ZTI-01intravenous fosfomycin (only antibiotic in phosphonic acid derivative class) 6g |
| Supra-therapeutic ZTI-01 12 g IV | Experimental | Drug: ZTI-01intravenous fosfomycin (only antibiotic in phosphonic acid derivative class) 12g |
| moxifloxacin 400 mg PO | Active comparator | Drug: Moxifloxacin 400mg, Other: Placebo IVoral moxifloxacin 400mg film coated tablets - Avelox(TM) |
| Placebo IV | Placebo comparator | Other: Placebo IVIV 0.9% normal saline solution |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- physically and mentally healthy volunteer
- a man or woman, 18 to 55 years of age
- a woman of childbearing potential using birth control / negative pregnancy test or a woman of non-childbearing potential
- males with female partners of childbearing potential agree to use contraception
- body mass index 19.0 to 32.0 kg/m2; weight of at least 60.0 kg at Screening
Key exclusion criteria (28 listed)
- History or evidence of cerebrovascular or cardiac disease
- Uncontrolled hypertension
- Electrographically significant abnormalities on ECG
- Clinically significant medical history (PI assessment)
- Clinically relevant lab abnormalities (PI assessment)
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 |
|---|---|---|
| ZTI-01Also: IV fosfomycin, fosfomycin disodium, fosfomycin for injection6g IV fosfomycin | Drug | Supra-therapeutic ZTI-01 12 g IV, Therapeutic ZTI-01 6 g IV |
| Moxifloxacin 400mgAlso: Positive controloral moxifloxacin (Avelox 400 mg) + IV normal saline (Placebo) | Drug | moxifloxacin 400 mg PO |
| Placebo IVAlso: Negative ControlIV Placebo (0.9% Normal Saline) | Other | Placebo IV, moxifloxacin 400 mg PO |
Primary outcome
Effect of ZTI-01 at the therapeutic and supra-therapeutic plasma concentration on cardiac repolarization expressed by QT interval
Time frame: 24 hour Holter ECG at Baseline (Day -1) & day of dosing (Day 1) in each of 4 periods. 10 replicates per time point at 13 timepoints: pre-dose: 60, 45 and 30 minutes; after the start of infusion: 0.5, 1 (end infusion), 1.25, 1.5, 2, 3, 4, 8, 12, & 24 hrs
Determine the change-from-baseline QTc (ΔQTc) when compared with placebo, and moxifloxacin (400 mg PO)
1 secondary outcome
Treatment emergent adverse events (TEAEs)
Time frame: From Day 1 start of dosing up to Day 36-38 (final follow up visit)
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 6 Mar 2019.
- Individual participant dataSharing planned: Undecided. final report, publication
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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.
Evelyn J Ellis-Grosse, PhD study chair
Chief Scientific Officer
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 ZTI-01 and Moxifloxacin 400mg in people with Cardiac Repolarization in Healthy Subjects, run by Nabriva Therapeutics AG 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 6 inclusion and 28 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 6 Mar 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?
Effect of ZTI-01 at the therapeutic and supra-therapeutic plasma concentration on cardiac repolarization expressed by QT interval (time frame: 24 hour Holter ECG at Baseline (Day -1) & day of dosing (Day 1) in each of 4 periods. 10 replicates per time point at 13 timepoints: pre-dose: 60, 45 and 30 minutes; after the start of infusion: 0.5, 1 (end infusion), 1.25, 1.5, 2, 3, 4, 8, 12, & 24 hrs). 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 6 Mar 2019.