Open-Label Phase 1 Study of Aerosolized Amikacin and Fosfomycin in Healthy Volunteers

July 8, 2016 updated by: Cardeas Pharma

An Open-Label Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the PARI Investigational eFlow Nebulizer System or the PARI LC Sprint Nebulizer in Healthy Volunteers

This study will evaluate systemic and urine pharmacokinetics in spontaneously breathing healthy volunteers following a single dose of amikacin/fosfomycin, using the PARI Investigational eFlow Nebulizer System or the PARI LC Sprint Nebulizer. Three doses (30/12 mg, 60/24 mg, 90/36 mg amikacin/fosfomycin) will be evaluated. Following this evaluation, a single dose and nebulizer will be chosen to further evaluate systemic, bronchoalveolar, and urine pharmacokinetics in spontaneously breathing healthy volunteers.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase 1 open-label study of three doses of amikacin/fosfomycin. Approximately 30 healthy volunteers will be dosed in five cohorts of six subjects each. The first (sentinel) subject in each of the first three cohorts will be dosed alone. If no significant safety or tolerability events occur, the remaining five subjects in each of the first three cohorts will be dosed. The first cohort (n=6) will be administered the 30/12 mg dose of amikacin/fosfomycin. The second cohort (n=6) will be administered the 60/24 mg dose of amikacin/fosfomycin. The third cohort (n=6) will be administered the 90/36 mg dose of amikacin/fosfomycin. All doses in cohorts 1, 2, and 3 will be delivered with the PARI Investigational eFlow Nebulizer System. The fourth cohort (n=6) will be administered the 90/36 mg dose of amikacin/fosfomycin using the PARI LC Sprint Nebulizer. The fifth cohort (n=6) will test the lowest dose level at which all subjects achieved > 0.3 µg/mL amikacin peak serum concentration. The nebulizer used to deliver doses in cohort 5 will be determined after amikacin concentrations from cohorts 1 through 4 are reviewed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • DaVita Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females aged ≥18 years and ≤ 80 years of age (Cohorts 1, 2, 3, and 4). Males or females aged ≥ 18 years and ≤ 65 years of age (Cohort 5).
  • Females of childbearing potential must be using contraception. Acceptable methods of contraception include male or female condom with spermicide gel or foam, hormonal contraceptive combined with a condom, Intrauterine Device (IUD), tubal ligation, diaphragm with spermicide, or total abstinence with a back-up if the subject becomes active.
  • Able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form.

Exclusion Criteria:

  • History of previous allergy or sensitivity to amikacin or fosfomycin.
  • Use of oral fosfomycin in the 28 days prior to admission to Phase 1 facility.
  • History of reactive airways disease (such as asthma or chronic obstructive pulmonary disease [COPD]), cystic fibrosis, or bronchiectasis.
  • Human Immunodeficiency Virus (HIV) positive.
  • Active Hepatitis B or C.
  • Cigarette/e-Cigarette smoking or use of other nicotine or tobacco containing products within seven days prior to study drug administration.

  • Positive for drugs of abuse or alcohol use at screening or admission to Phase 1 facility. A Breathalyzer test will be used to screen for the presence of alcohol. A urine standard panel will be used to test for the following substances (with serum testing for confirmation, as needed):

    • Opiates
    • Oxycodone
    • Methadone
    • Cocaine
    • Tetrahydrocannabinol (THC)
    • Benzodiazepines
    • Amphetamines / Methamphetamines
    • Barbiturates
    • Methylenedioxy-methamphetamine (MDMA)
    • Phenylcyclohexyl piperidine (PCP)
    • Tricyclic Antidepressants
  • Participation in a clinical study with administration of an investigational drug product within the previous 30 days, or five half-lives of the previously administered investigational product.
  • Donation of blood or significant blood loss within the 8 weeks prior to admission to Phase 1 facility.
  • Donation of plasma within the week prior to admission to Phase 1 facility.
  • Any other condition which in the view of the Investigator is likely to interfere with the study or put the subject at risk.
  • Pregnant or nursing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
amikacin/fosfomycin (30/12 mg) delivered via the PARI Investigational eFlow Nebulizer (single dose)
Drug: amikacin/fosfomycin
single aerosolized dose
Experimental: Cohort 2
amikacin/fosfomycin (60/24 mg) delivered via the PARI Investigational eFlow Nebulizer (single dose)
Drug: amikacin/fosfomycin
single aerosolized dose
Experimental: Cohort 3
amikacin/fosfomycin (90/36 mg) delivered via the PARI Investigational eFlow Nebulizer (single dose)
Drug: amikacin/fosfomycin
single aerosolized dose
Experimental: Cohort 4
amikacin/fosfomycin (90/36 mg) delivered via the PARI LC Sprint Nebulizer (single dose)
Drug: amikacin/fosfomycin
single aerosolized dose
Experimental: Cohort 5
amikacin/fosfomycin (Dose and Nebulizer to be chosen based on results from Cohorts 1 - 4)
Drug: amikacin/fosfomycin
single aerosolized dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Peak plasma concentration (Cmax) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI Investigational eFlow Nebulizer System
Time Frame: 10 minutes to 24 hours post-dose
10 minutes to 24 hours post-dose
Peak plasma concentration (Cmax) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI LC Sprint Nebulizer
Time Frame: 10 minutes to 24 hours post-dose
10 minutes to 24 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to peak plasma concentration (Tmax) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI Investigational eFlow Nebulizer System
Time Frame: 10 minutes to 24 hours post-dose
10 minutes to 24 hours post-dose
Time to peak plasma concentration (Tmax) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI LC Sprint Nebulizer
Time Frame: 10 minutes to 24 hours post-dose
10 minutes to 24 hours post-dose
Plasma area under the concentration-time curve (AUC) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI Investigational eFlow Nebulizer System
Time Frame: 10 minutes to 24 hours post-dose
10 minutes to 24 hours post-dose
Plasma area under the concentration-time curve (AUC) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI LC Sprint Nebulizer
Time Frame: 10 minutes to 24 hours post-dose
10 minutes to 24 hours post-dose
Peak bronchoalveolar lavage concentration (Cmax) of amikacin/fosfomycin following delivery of nebulized 30/12 mg, 60/24 mg, or 90/36 mg amikacin/fosfomycin via the PARI Investigational eFlow Nebulizer System or the PARI LC Sprint Nebulizer
Time Frame: 30 minutes post-dose
The dose and nebulizer used for Cohort 5 will be chosen based on plasma Cmax results from Cohorts 1 - 4.
30 minutes post-dose

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Peak urine concentration (Cmax) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI Investigational eFlow Nebulizer System
Time Frame: 0 - 6 hours; 6 - 12 hours; and 12 - 24 hours post-dose
0 - 6 hours; 6 - 12 hours; and 12 - 24 hours post-dose
Peak urine concentration (Cmax) of nebulized amikacin/fosfomycin following delivery of 30/12 mg, 60/24 mg, and 90/36 mg amikacin/fosfomycin via the PARI LC Sprint Nebulizer
Time Frame: 0 - 6 hours; 6 - 12 hours; and 12 - 24 hours post-dose
0 - 6 hours; 6 - 12 hours; and 12 - 24 hours post-dose
Number of subjects with treatment-related adverse events
Time Frame: 0 - 24 hours post-dose
0 - 24 hours post-dose
Change in lung function from pre-dose to post-dose
Time Frame: pre-dose to 15 minutes post-dose
Spirometry (forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow in the middle 50% of the exhaled volume) will be measured prior to dosing with study drug and 15 minutes after completing the dose of study drug
pre-dose to 15 minutes post-dose
Change in vital signs from pre-dose to post-dose
Time Frame: pre-dose to 15 minutes post-dose
Vital signs (heart rate, respiratory rate, blood pressure, and oximetry) will be measured prior to dosing with study drug and 15 minutes after completing the dose of study drug
pre-dose to 15 minutes post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cardeas Pharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2016

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAP-01-104

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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