Investigation of AAI101 Safety, Tolerability & PK in Healthy Volunteers

NCT03685084 | Completed Phase 1

• 1 other identifier: AT-101
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• AAI101 maximum plasma concentration (Cmax)

  Up to 24 hours post-dose

• AAI101 Clast

  Up to 24 hours post-dose

• AAI101 AUC(0-t) - AUC(0-8)

  Up to 24 hours post-dose

• AAI101 half life (t1/2)

  Up to 24 hours post-dose

Study Arms (4)

0.9% saline infusion

PLACEBO COMPARATOR

Saline 0.9% infusion

Drug: AAI101 i.v.; Drug: Saline 0.9% infusion

AAI101 i.v.

EXPERIMENTAL

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.; Drug: Saline 0.9% infusion

Piperacillin i.v.

EXPERIMENTAL

Piperacillin 3 g

Drug: Piperacillin i.v.

Cefepime i.v.

EXPERIMENTAL

Cefepime 1 g

Drug: Cefepime i.v.

Interventions

AAI101 i.v. DRUG

600 mg, 1 g, 2 g, 4 g, 1 g (every 6h), 2 g (every 6h)

Also known as: AAI101

0.9% saline infusion; AAI101 i.v.

Saline 0.9% infusion DRUG

Vehicle infusion

Also known as: Vehicle

0.9% saline infusion; AAI101 i.v.

Piperacillin i.v. DRUG

piperacillin 3 g i.v.

Also known as: Beta-lactam antibiotic

Piperacillin i.v.

Cefepime i.v. DRUG

cefepime 1 g i.v.

Also known as: Beta-lactam antibiotic

Cefepime i.v.

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Healthy male subjects
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Allecra: lead

MeSH Terms

Interventions

enmetazobactam; Sodium Chloride; Monobactams

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 26, 2018
• Study Start: October 10, 2013
• Primary Completion: January 13, 2014
• Study Completion: January 13, 2014
• Last Updated: September 26, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share