Pseudomonas InfectionPhase 1NCT02178254
Safety, Tolerability and PK 3-Period Crossover Study Comparing 2 Single Doses of ZTI-01 and Monurol® in Healthy Subjects
A Phase 1 study testing Fosfomycin tromethamine and Fosfomycin disodium in people with Pseudomonas Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The objective is to determine the safety, tolerability and pharmacokinetics (PK) of 2 single doses of ZTI-01 (1g and 8g infused over 1-hr) and a single dose of the Reference Label Drug, Monurol® (oral sachet, 3g). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Pseudomonas Infection
- What is being tested?
- Fosfomycin tromethamine and Fosfomycin disodium
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Oct 2014
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- To be considered for study enrollment, subjects must meet all of the inclusion criteria:
- Healthy men and women from 18 to 45 years of age with no clinically significant findings on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) or clinical laboratory evaluation that were performed at Screening and Day -1.
- Body Mass Index (BMI) between 18-30 kg/m^2, inclusive; and a total body weight > 50 kg (110 lbs).
- Post-menopausal women with amenorrhea for at least 2 years with an FSH in the post-menopausal range as well as surgically sterile women (documented history of oophorectomy and/or hysterectomy, tubal ligation or tubal occlusion) will be eligible.
- Females of childbearing potential must use an acceptable birth control method (e.g., condom plus spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) throughout the study and for 4 weeks following initiation of dosing with study drug.
- Male subjects must either had a vasectomy or agree to use a double barrier method of contraception, condom plus spermicide (or diaphragm plus spermicide in female partner) from the time of dosing with the study drug in Period 1 through 4 weeks following initiation of dosing with study drug.
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- Nicotine-free by history (cigarettes, pipe, cigar, chewing tobacco, nicotine patch) for at least 30 days before Day -1 and urine cotinine at pre-study screening and Day -1 <400 ng/mL).
- Able to abstain from grapefruit, grapefruit juice, grapefruit-containing products or alcoholic beverages within 48 hours before Day -1 and throughout the inpatient period.
- Willing to remain in the study facility and agree to abide to the Quintiles Phase 1 Unit House Rules for the duration of the inpatient study period.
- Have a high probability for compliance and completion of the study.
- Sign a dated, witnessed, written informed consent form
Who cannot join
- Subjects must meet none of the following study criteria at Study Day -1, Period 1:
- History or presence of any psychiatric or emotional disorder that might prevent the successful completion of the study.
- Any surgical or medical condition that in the opinion of the investigator could interfere with drug absorption, distribution, metabolism, or excretion or any condition that may place the subject at increased risk while participating in the study. Examples of the conditions for exclusion: previous bariatric surgery, cardiovascular disease, renal impairment, renal disease, liver disease, chronic pulmonary disease, venous insufficiency, peripheral edema, borderline hypertension systolic pressure over > 140mmHg and or diastolic pressure >90 mmHg, serum sodium or liver enzymes above the upper limit, Regarding the last two conditions, one repeat is allowed at both screening and check-in to determine eligibility.
- Any history or presence of clinically significant allergic conditions (e.g., recurrent dermatitis or drug hypersensitivity reactions).
- Have cancer or have a history of cancer (with exceptions of a few types of cancer, e.g. recent removal of basal cell skin carcinoma) within the past five years.
- Irritable bowel syndrome or any gastrointestinal disease (including frequent nausea due to migraine) within 30 days prior to study day 1, Period 1.
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- History or presence of lactose intolerance.
- History of alcohol abuse within 12 months of study day 1, Period 1.
- History of intolerance or hypersensitivity to phosphonic acid derivative antibiotics or any of its constituents
- Use of any prescription drugs within 30 days of administration of the study drug
- Involvement in other investigational studies of any type (drugs, devices, procedures) within 30 days of screening.
- Blood or blood products donation within 60 days of Day -1.
- Use of any non-prescription medications, vitamins, licorice (in large amounts) or dietary supplements within 7 days of administration of the study drug. Excluded from this list is intermittent use of acetaminophen at doses of </=2 g/day. Herbal supplements must be discontinued 7 days prior to the initial dose of study drug.
- Consumption of more than 300 mg of caffeine per day (>3 cups of coffee or 6-12 ounces of soda) within 7 days prior to dosing.
- Presence of any acute illness within 7 days of Day -1 in any Study Period.
- Breastfeeding or a positive serum pregnancy test at the Screening Visit or on Day -1 in any Study Period
- Positive tests for human immunodeficiency virus (HIV 1 and 2) antibodies, hepatitis B surface antigen (HBsAg) and/or hepatitis C (HCV) antibody.
- Positive urine drug or alcohol screen at the Screening Visit or on Day -1
- Weight loss or gain of > 10 percent within 30 days of Day -1.
- Females whose hemoglobin is <11.8 g/dL or males whose hemoglobin is <13.8g/dL.
Trial locations and contacts
1 site in 1 country.
United States1 site
Quintiles Phase I Services - Overland Park
Overland Park, Kansas, 66211-1553
About this study
Official title: A Randomized, Safety, Tolerability and Pharmacokinetics 3-Period Crossover Study Comparing 2 Single Doses of ZTI-01 and Monurol® in Healthy Subjects
The objective is to determine the safety, tolerability and pharmacokinetics (PK) of 2 single doses of ZTI-01 (1g and 8g infused over 1-hr) and a single dose of the Reference Label Drug, Monurol® (oral sachet, 3g). Subjects will be randomized to a treatment sequence prior to dosing on Day 1 of Period 1 prior to study screening.
Read the detailed description
This is a Phase 1 single-dose, randomized, 3-Period, crossover study conducted at a single center. A total of 30 healthy subjects, aged 18-45years, will be randomized to receive one of 3 treatment sequences. The duration of study will be approximately 18-26 days and subject participation will be the duration of study. Each treatment sequence will be enrolled in parallel and each subject will receive all 3 treatments in crossover fashion. Each subject will complete Screening, Baseline, and Treatment Phases. The Screening Phase will be conducted on an outpatient basis within 35 days of admission (Day -1 of Period 1). All subjects admitted to the study center the day before dosing in each treatment period (Day -1; check-in) for pre-dosing assessments and will remain in the study center through 48 hours post-dose for each Period. Final baseline qualification will only be evaluated prior to randomization for Treatment Period 1. Each one of the periods will be separated by a 3 (minimum) to 7 days (maximum) washout period. The Treatment Phase will be comprised of 3 crossover periods (duration Day-1 to 48 hours post dose). Each crossover period will include a single dose of study drug under fasting conditions followed by post-dose safety assessments and blood and urine collection for PK measures through 48 hours post-dose; each period will be separated by a 3 to 7 days washout. Subjects will remain in the study center for all 3- study treatment periods (Day -1 to 48 hours post dosing) and will be discharged after the 48-hour sampling timepoint (if safety parameters are acceptable to the Investigator on Day 3).
- Conditions
- Pseudomonas Infection
- Being tested
- Fosfomycin tromethamine, Fosfomycin disodium
- Keywords
- Pseudomonas aeruginosa, ZTI-101, phosphonic acid derivative, Monurol, fosfomycin tromethamine
- Medical subject headings
- Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fosfomycin tromethamineDrug
A phosphonic acid derivative is the mono-acid salt of Fosfomycin with Tromethamine. Sequence 1-3 receive 3 grams oral sachet
Fosfomycin disodiumDrug
ZTI-01 is a phosphonic acid derivative formulated as a disodium salt intravenous formulation. ZTI-01 acts by inhibiting peptidoglycan assembly, thereby disrupting cell wall synthesis. Sequence 1-3 receive 1 gram and 8 grams of Intravenous ZTI-01 for 1-hour infusion
| Study group | Role | What they receive |
|---|---|---|
| Sequence 3 | Experimental | N=10 subjects receive 3grams oral sachet of Monurol in Period 1; 1.0gram of Intravenous (IV) ZTI-01 for Period 2 (1-hour infusion); and 8.0 grams IV ZTI-01 for Period 3. Receives: Drug: Fosfomycin tromethamine; Drug: Fosfomycin disodium |
| Sequence 1 | Experimental | N=10 subjects receive 1.0gram of Intravenous (IV) ZTI-01 for Period 1 (1-hour infusion); 8.0 grams IV ZTI-01 for Period 2 (1-hour infusion); and 3grams oral sachet of Monurol in Period 3. Receives: Drug: Fosfomycin tromethamine; Drug: Fosfomycin disodium |
| Sequence 2 | Experimental | N=10 subjects receive 8.0 grams IV ZTI-01 for Period 1(1-hour infusion); 3grams oral sachet of Monurol in Period 2 and 1.0gram of IV ZTI-01 for Period 3 (1-hour infusion) Receives: Drug: Fosfomycin tromethamine; Drug: Fosfomycin disodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics: Maximum measured plasma concentration (Cmax), area under the concentration versus time curve (AUC0-t and AUC0-inf), time to peak concentration (tmax), terminal elimination half-life (t1/2), terminal-phase elimination rate constant).
Measured: Study periods 1, 2 and 3, Day 1 through Day 3
Pharmacokinetics: Volume of distribution (Vd) or apparent volume of distribution (Vd/F) as appropriate, clearance (CL) or apparent Clearance (CL/F) as appropriate, renal Clearance (CLr) and Fraction Bioavailable as appropriate
Measured: Study periods 1, 2 and 3, Day 1 through Day 3
Adverse events (AEs) will be monitored and recorded
Measured: Study periods 1, 2 and 3, screening through Day 3, including washout periods
Assessed safety and tolerability via physical examinations, vital signs, standard 12-lead electrocardiograms, and clinical laboratory tests
Measured: Study periods 1, 2 and 3, screening through Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2014 (estimated)
- Study startAug 2014
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pseudomonas InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02178254
- Sponsor's protocol ID
- 13-0064
- Other IDs
- HHSN272201500005I
- Status last verified
- Jan 2015
- First submitted
- 26 Jun 2014
- Last updated
- 4 Apr 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Safety, Tolerability and Pharmacokinetics 3-Period Crossover Study Comparing 2 Single Doses of ZTI-01 and Monurol® in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02178254
- Acronym / sponsor ID
- 13-0064
- Conditions
- Pseudomonas Infection
- Keywords
- Pseudomonas aeruginosa, ZTI-101, phosphonic acid derivative, Monurol, fosfomycin tromethamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Aug 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 30 Jun 2014 (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.
The objective is to determine the safety, tolerability and pharmacokinetics (PK) of 2 single doses of ZTI-01 (1g and 8g infused over 1-hr) and a single dose of the Reference Label Drug, Monurol® (oral sachet, 3g). Subjects will be randomized to a treatment sequence prior to dosing on Day 1 of Period 1 prior to study screening.
Detailed description
This is a Phase 1 single-dose, randomized, 3-Period, crossover study conducted at a single center. A total of 30 healthy subjects, aged 18-45years, will be randomized to receive one of 3 treatment sequences. The duration of study will be approximately 18-26 days and subject participation will be the duration of study. Each treatment sequence will be enrolled in parallel and each subject will receive all 3 treatments in crossover fashion. Each subject will complete Screening, Baseline, and Treatment Phases. The Screening Phase will be conducted on an outpatient basis within 35 days of admission (Day -1 of Period 1). All subjects admitted to the study center the day before dosing in each treatment period (Day -1; check-in) for pre-dosing assessments and will remain in the study center through 48 hours post-dose for each Period. Final baseline qualification will only be evaluated prior to randomization for Treatment Period 1. Each one of the periods will be separated by a 3 (minimum) to 7 days (maximum) washout period. The Treatment Phase will be comprised of 3 crossover periods (duration Day-1 to 48 hours post dose). Each crossover period will include a single dose of study drug under fasting conditions followed by post-dose safety assessments and blood and urine collection for PK measures through 48 hours post-dose; each period will be separated by a 3 to 7 days washout. Subjects will remain in the study center for all 3- study treatment periods (Day -1 to 48 hours post dosing) and will be discharged after the 48-hour sampling timepoint (if safety parameters are acceptable to the Investigator on Day 3).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sequence 3 | Experimental | Drug: Fosfomycin tromethamine, Drug: Fosfomycin disodiumN=10 subjects receive 3grams oral sachet of Monurol in Period 1; 1.0gram of Intravenous (IV) ZTI-01 for Period 2 (1-hour infusion); and 8.0 grams IV ZTI-01 for Period 3. |
| Sequence 1 | Experimental | Drug: Fosfomycin tromethamine, Drug: Fosfomycin disodiumN=10 subjects receive 1.0gram of Intravenous (IV) ZTI-01 for Period 1 (1-hour infusion); 8.0 grams IV ZTI-01 for Period 2 (1-hour infusion); and 3grams oral sachet of Monurol in Period 3. |
| Sequence 2 | Experimental | Drug: Fosfomycin tromethamine, Drug: Fosfomycin disodiumN=10 subjects receive 8.0 grams IV ZTI-01 for Period 1(1-hour infusion); 3grams oral sachet of Monurol in Period 2 and 1.0gram of IV ZTI-01 for Period 3 (1-hour infusion) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy men and women from 18 to 45 years of age with no clinically significant findings on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) or clinical laboratory evaluation that were performed at Screening and Day -1.
- Body Mass Index (BMI) between 18-30 kg/m^2, inclusive; and a total body weight > 50 kg (110 lbs).
- Post-menopausal women with amenorrhea for at least 2 years with an FSH in the post-menopausal range as well as surgically sterile women (documented history of oophorectomy and/or hysterectomy, tubal ligation or tubal occlusion) will be eligible.
- Females of childbearing potential must use an acceptable birth control method (e.g., condom plus spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) throughout the study and for 4 weeks following initiation of dosing with study drug.
- Male subjects must either had a vasectomy or agree to use a double barrier method of contraception, condom plus spermicide (or diaphragm plus spermicide in female partner) from the time of dosing with the study drug in Period 1 through 4 weeks following initiation of dosing with study drug.
Key exclusion criteria (20 listed)
- History or presence of any psychiatric or emotional disorder that might prevent the successful completion of the study.
- Any surgical or medical condition that in the opinion of the investigator could interfere with drug absorption, distribution, metabolism, or excretion or any condition that may place the subject at increased risk while participating in the study. Examples of the conditions for exclusion: previous bariatric surgery, cardiovascular disease, renal impairment, renal disease, liver disease, chronic pulmonary disease, venous insufficiency, peripheral edema, borderline hypertension systolic pressure over > 140mmHg and or diastolic pressure >90 mmHg, serum sodium or liver enzymes above the upper limit, Regarding the last two conditions, one repeat is allowed at both screening and check-in to determine eligibility.
- Any history or presence of clinically significant allergic conditions (e.g., recurrent dermatitis or drug hypersensitivity reactions).
- Have cancer or have a history of cancer (with exceptions of a few types of cancer, e.g. recent removal of basal cell skin carcinoma) within the past five years.
- Irritable bowel syndrome or any gastrointestinal disease (including frequent nausea due to migraine) within 30 days prior to study day 1, Period 1.
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 |
|---|---|---|
| Fosfomycin tromethamineA phosphonic acid derivative is the mono-acid salt of Fosfomycin with Tromethamine. Sequence 1-3 receive 3 grams oral sachet | Drug | Sequence 1, Sequence 2, Sequence 3 |
| Fosfomycin disodiumZTI-01 is a phosphonic acid derivative formulated as a disodium salt intravenous formulation. ZTI-01 acts by inhibiting peptidoglycan assembly, thereby disrupting cell wall synthesis. Sequence 1-3 receive 1 gram and 8 grams of Intravenous ZTI-01 for 1-hour infusion | Drug | Sequence 1, Sequence 2, Sequence 3 |
Primary outcome
Pharmacokinetics: Maximum measured plasma concentration (Cmax), area under the concentration versus time curve (AUC0-t and AUC0-inf), time to peak concentration (tmax), terminal elimination half-life (t1/2), terminal-phase elimination rate constant).
Time frame: Study periods 1, 2 and 3, Day 1 through Day 3
Pharmacokinetics: Volume of distribution (Vd) or apparent volume of distribution (Vd/F) as appropriate, clearance (CL) or apparent Clearance (CL/F) as appropriate, renal Clearance (CLr) and Fraction Bioavailable as appropriate
Time frame: Study periods 1, 2 and 3, Day 1 through Day 3
Adverse events (AEs) will be monitored and recorded
Time frame: Study periods 1, 2 and 3, screening through Day 3, including washout periods
Assessed safety and tolerability via physical examinations, vital signs, standard 12-lead electrocardiograms, and clinical laboratory tests
Time frame: Study periods 1, 2 and 3, screening through Day 3
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 4 Apr 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Fosfomycin tromethamine and Fosfomycin disodium in people with Pseudomonas Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 11 inclusion and 20 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 4 Apr 2016. 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. 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?
Pharmacokinetics: Maximum measured plasma concentration (Cmax), area under the concentration versus time curve (AUC0-t and AUC0-inf), time to peak concentration (tmax), terminal elimination half-life (t1/2), terminal-phase elimination rate constant). (time frame: Study periods 1, 2 and 3, Day 1 through Day 3). The study lists 4 primary outcomes in all. 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 4 Apr 2016; AzTrials last refreshed its copy on 31 Oct 2026.