DDI Study to Investigate Interaction Between Amikacin and POL7080

Study Overview
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Brief Summary
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Single-center, open-label, 2-sequence, 3-period crossover drug-drug interaction study. Repeated doses of POL7080 and repeated doses of amikacin will be administered alone or combined. In total, 14 subjects will be enrolled to obtain at least 10 evaluable subjects. The study consists of an eligibility screening period, up to 3 treatments periods and a follow-up visit.

Official Title
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A Single-center, Open-label, Two Sequence, Crossover Study to Investigate the Interaction Between Amikacin and POL7080 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: POL7080
* Drug: Amikacin
* Drug: POL7080 + Amikacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female (of non-childbearing potential) subjects between 18 to 55 years of age (inclusive) BMI between 18.0-30.0 kg/m2 Creatinine clearance estimated by Cockroft Gault formula > 80 mL/min and < 160 ml/min (for males), or < 150ml/min (females) Non smokers Normal audiogram. Exclusion Criteria: History or suspicion of alcohol and/or drug abuse in the last 5 years Within 2 months prior to screening: exposure to aminoglycoside antibiotic, chemotherapy, or current use of loop diuretics Regular consumption of large amounts of xanthine Any medication that inhibits active tubular secretion within 4 weeks prior to first dosing Infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) Any signs of renal impairment Clinically significant abnormalities (e.g. cardiovascular, laboratory values) Clinically significant abnormal ECG

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1<br>Participants will be randomized to one of two treatment sequences. Sequence 1 is: Period 1, POL7080; Period 2, Amikacin; Period 3,POL7080+Amikacin. Each period is separated by a wash-out period of at least 12 days between last dose and start of next treatment. | Drug: POL7080<br>* 7 doses of POL7080 alone over 2.5 days<br>Drug: Amikacin<br>* 3 doses of Amikacin alone over 2.5 days<br>Drug: POL7080 + Amikacin<br>* 7 doses of POL7080 and 3 doses of Amikacin over 2.5 days<br>|
| Experimental: Treatment sequence 2<br>Participants will be randomized to one of two treatment sequences. Sequence 1 is: Period 1, Amikacin; Period 2, POL7080; Period 3,POL7080+Amikacin. Each period is separated by a wash-out period of at least 12 days between last dose and start of next treatment. | Drug: POL7080<br>* 7 doses of POL7080 alone over 2.5 days<br>Drug: Amikacin<br>* 3 doses of Amikacin alone over 2.5 days<br>Drug: POL7080 + Amikacin<br>* 7 doses of POL7080 and 3 doses of Amikacin over 2.5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple dose pharmacokinetics of POL7080 and Amikacin (as appropriate): Peak Plasma Concentration (Cmax) |  | Up to 4 days for each period | 
| Multiple dose pharmacokinetics of POL7080 and Amikacin (as appropriate):Area under the plasma concentration versus time curve (AUC) |  | Up to 4 days for each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse Events |  | up to 19 days |