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

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: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: amikacin/fosfomycin

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: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 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

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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	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	10 minutes to 24 hours post-dose

Secondary Outcome Measures

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		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		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		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		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	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

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		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		0 - 6 hours; 6 - 12 hours; and 12 - 24 hours post-dose
Number of subjects with treatment-related adverse events		0 - 24 hours post-dose
Change in lung function from pre-dose to 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	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

• Sponsor: Cardeas Pharma

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: March 8, 2016
• First Submitted That Met QC Criteria: March 10, 2016
• First Posted (Estimate): March 16, 2016

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: July 8, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Amikacin; Fosfomycin
• Other Study ID Numbers: CAP-01-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No