Investigation of AAI101 Safety, Tolerability & PK in Healthy Volunteers

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

• 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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AAI101 i.v.; Drug: Saline 0.9% infusion; Drug: Piperacillin i.v.; Drug: Cefepime i.v.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 0.9% saline infusion; Saline 0.9% infusion	Drug: AAI101 i.v.; 600 mg, 1 g, 2 g, 4 g, 1 g (every 6h), 2 g (every 6h); Other Names: AAI101; Drug: Saline 0.9% infusion; Vehicle infusion; Other Names: Vehicle
Experimental: 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.	Drug: AAI101 i.v.; 600 mg, 1 g, 2 g, 4 g, 1 g (every 6h), 2 g (every 6h); Other Names: AAI101; Drug: Saline 0.9% infusion; Vehicle infusion; Other Names: Vehicle
Experimental: Piperacillin i.v.; Piperacillin 3 g	Drug: Piperacillin i.v.; piperacillin 3 g i.v.; Other Names: Beta-lactam antibiotic
Experimental: Cefepime i.v.; Cefepime 1 g	Drug: Cefepime i.v.; cefepime 1 g i.v.; Other Names: Beta-lactam antibiotic

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Allecra

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2013
• Primary Completion (Actual): January 13, 2014
• Study Completion (Actual): January 13, 2014

Study Registration Dates

• First Submitted: September 19, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): September 26, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antitubercular Agents; beta-Lactamase Inhibitors; Anti-Bacterial Agents; Antibiotics, Antitubercular; Piperacillin; Lactams; Cefepime; beta-Lactams; Enmetazobactam
• Other Study ID Numbers: AT-101

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No