Investigation of AAI101 Safety, Tolerability & PK in Healthy Volunteers

Study Overview
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Brief Summary
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To assess the safety and tolerability of single and multiple ascending intravenous doses of AAI101 (SAD & MAD) in healthy male subjects. To assess the safety and tolerability of single and multiple ascending intravenous doses of AAI101 in combination with fixed intravenous doses of piperacillin or cefepime in healthy male subjects

Official Title
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Phase I, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of AAI101 Administered Intravenously Alone or in Combination With Piperacillin or Cefepime to Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: AAI101 i.v.
* Drug: Saline 0.9% infusion
* Drug: Piperacillin i.v.
* Drug: Cefepime i.v.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male healthy volunteers aged between 18 and 45 years (inclusive) at screening. Body mass index (BMI) of 18.0 to 30.0 Kg/m2 (inclusive) at screening. Healthy as determined by the investigator on the basis of medical history, physical examination findings, clinical laboratory test results, vital sign measurements, and digital 12 lead ECG readings (all results were to be within normal range or considered non-clinically significant by the investigator). Non-smoker or smoker of fewer than 10 cigarettes per day as determined by medical history. Had to be able to abstain from smoking during the inpatient stay. Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study. Main Exclusion Criteria: Any significant cardiovascular (e.g., hypertension), hepatic, renal, respiratory (e.g., childhood asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia), immunologic, hematological, neurologic, or psychiatric disease. Acute disease state (e.g., nausea, vomiting, fever, diarrhea) within 7 days before study Day 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 0.9% saline infusion<br>Saline 0.9% infusion | Drug: AAI101 i.v.<br>* 600 mg, 1 g, 2 g, 4 g, 1 g (every 6h), 2 g (every 6h)<br>* Other names: AAI101;Drug: Saline 0.9% infusion<br>* Vehicle infusion<br>* Other names: Vehicle;|
| Experimental: AAI101 i.v.<br>600 mg, 1g, 2g, 4g, 1g q6h, 2g q6h. Drug-Drug Interaction: Sequence 1 = piperacillin 4 g i.v. - AAI101 2 g i.v. - AAI101 2 g + piperacillin 4 g i.v. - cefepime 2 g i.v. - AAI101 2 g + cefepime 2 g i.v. Sequence 2 = cefepime 2 g i.v. - piperacillin 4 g i.v. - AAI101 2 g + cefepime 2 g i.v. - AAI101 2 g i.v. - AAI101 2 g + piperacillin 4 g i.v. | Drug: AAI101 i.v.<br>* 600 mg, 1 g, 2 g, 4 g, 1 g (every 6h), 2 g (every 6h)<br>* Other names: AAI101;Drug: Saline 0.9% infusion<br>* Vehicle infusion<br>* Other names: Vehicle;|
| Experimental: Piperacillin i.v.<br>Piperacillin 3 g | Drug: Piperacillin i.v.<br>* piperacillin 3 g i.v.<br>* Other names: Beta-lactam antibiotic;|
| Experimental: Cefepime i.v.<br>Cefepime 1 g | Drug: Cefepime i.v.<br>* cefepime 1 g i.v.<br>* Other names: Beta-lactam antibiotic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile - Number of Subjects With at Least one Adverse Event | Safety will be evaluated from reported signs and symptoms and clinical laboratory tests | Throughout the period that subjects receive study drug up to 5 days following discontinuation of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AAI101 maximum plasma concentration (Cmax) | Cmax will be compared before and after administration of AAI101 either alone or in the presence of cefepime or piperacillin | Up to 24 hours post-dose | 
| AAI101 Clast | Clast will be compared before and after administration of AAI101 either alone or in the presence of cefepime or piperacillin | Up to 24 hours post-dose | 
| AAI101 AUC(0-t) - AUC(0-8) | AAI101 Urea Under the Curve will be compared before and after administration of AAI101 either alone or in the presence of cefepime or piperacillin | Up to 24 hours post-dose | 
| AAI101 half life (t1/2) | AAI101 t1/2 plasma pharmacokinetic parameter will be compared for AAI101 alone or in the presence of cefepime or piperacillin | Up to 24 hours post-dose |