Investigation of AAI101 Safety, Tolerability & PK in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT03685084
• Recruitment Status: Completed
• First Posted: September 26, 2018
• Last Update Posted: September 26, 2018
• Sponsor: Allecra
• Information provided by (Responsible Party): Allecra

Study Description

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: AAI101 i.v.; Drug: Saline 0.9% infusion; Drug: Piperacillin i.v.; Drug: Cefepime i.v.	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: October 10, 2013
• Actual Primary Completion Date: January 13, 2014
• Actual Study Completion Date: January 13, 2014

Arms and Interventions

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 Name: AAI101; Drug: Saline 0.9% infusion; Vehicle infusion; Other Name: 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 Name: AAI101; Drug: Saline 0.9% infusion; Vehicle infusion; Other Name: Vehicle
Experimental: Piperacillin i.v.; Piperacillin 3 g	Drug: Piperacillin i.v.; piperacillin 3 g i.v.; Other Name: Beta-lactam antibiotic
Experimental: Cefepime i.v.; Cefepime 1 g	Drug: Cefepime i.v.; cefepime 1 g i.v.; Other Name: Beta-lactam antibiotic

Outcome Measures

Primary Outcome Measures :

1. Safety Profile - Number of Subjects With at Least one Adverse Event [ Time Frame: 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 :

1. AAI101 maximum plasma concentration (Cmax) [ Time Frame: 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
2. AAI101 Clast [ Time Frame: 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
3. AAI101 AUC(0-t) - AUC(0-8) [ Time Frame: 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
4. AAI101 half life (t1/2) [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Healthy male subjects
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Allecra
• ClinicalTrials.gov Identifier: NCT03685084
• Other Study ID Numbers: AT-101
• First Posted: September 26, 2018
• Last Update Posted: September 26, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anti-Bacterial Agents; Piperacillin; Cefepime; Lactams; beta-Lactams; Enmetazobactam; Antibiotics, Antitubercular; Anti-Infective Agents; Antitubercular Agents; beta-Lactamase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action