Investigation of AAI101 Safety, Tolerability & PK in Healthy Volunteers
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT03685084
- Lead Sponsor
- Allecra
- Brief Summary
* 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 56
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Piperacillin i.v. Piperacillin i.v. Piperacillin 3 g AAI101 i.v. Saline 0.9% infusion 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. AAI101 i.v. AAI101 i.v. 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. Cefepime i.v. Cefepime i.v. Cefepime 1 g 0.9% saline infusion AAI101 i.v. Saline 0.9% infusion 0.9% saline infusion Saline 0.9% infusion Saline 0.9% infusion
- Primary Outcome Measures
Name Time Method Safety Profile - Number of Subjects With at Least one Adverse Event Throughout the period that subjects receive study drug up to 5 days following discontinuation of study treatment Safety will be evaluated from reported signs and symptoms and clinical laboratory tests
- Secondary Outcome Measures
Name Time Method AAI101 maximum plasma concentration (Cmax) Up to 24 hours post-dose Cmax will be compared before and after administration of AAI101 either alone or in the presence of cefepime or piperacillin
AAI101 Clast Up to 24 hours post-dose Clast will be compared before and after administration of AAI101 either alone or in the presence of cefepime or piperacillin
AAI101 AUC(0-t) - AUC(0-8) Up to 24 hours post-dose AAI101 Urea Under the Curve will be compared before and after administration of AAI101 either alone or in the presence of cefepime or piperacillin
AAI101 half life (t1/2) Up to 24 hours post-dose AAI101 t1/2 plasma pharmacokinetic parameter will be compared for AAI101 alone or in the presence of cefepime or piperacillin