A Study to Evaluate the Effect of IV ACHN-490 Injection on the QT/QTc Interval in Healthy Volunteers

NCT01514929 | Completed Phase 1 DMC

• 1 other identifier: ACHN-490-006
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the study drug, ACHN-490 Injection, affects the QT interval in normal volunteers. The hypothesis is that the drug will not cause an increase in the QT interval.

Conditions

Cardiac Effects in Normal Healthy Volunteers

Keywords

Thorough QT

Outcome Measures

Primary Outcomes (2)

• Safety

  In Part 1, the safety and tolerability of a single 20 mg/kg dose of ACHN-490 Injection will be assessed by measuring adverse events, blood pressure and other vital sign measurements, incidence and magnitude of clinically significant changes from baseline in clinical laboratory values (hematology, chemistry, and urinalysis), and physical examination, through 24 hours after study drug administration or resolution of all adverse events.

  1 day

• Effect of ACHN-490 Injection on QTcF

  The primary endpoint for Part 2 of this study is the time-matched change from baseline in QTcF within 24 hours of receiving study drug.

  24 hours

Secondary Outcomes (5)

• PK Parameters

  24 hours

• ECG Parameters

  24 hours

• PK Parameters

  24 hours

• Correlation between drug concentration and QTc

  24 hours

• Safety and tolerability

  Up to 44 days

Study Arms (4)

Supratherapeutic Dose

EXPERIMENTAL

20mg/kg ACHN-490 Injection

Drug: ACHN-490 Injection

Possible Therapeutic Dose

EXPERIMENTAL

15mg/kg ACHN-490 Injection

Drug: ACHN-490 Injection

Moxifloxacin

ACTIVE COMPARATOR

400mg moxifloxacin

Drug: Moxifloxacin

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

ACHN-490 Injection DRUG

20mg/kg IV 30 minute infusion given once

Supratherapeutic Dose

Moxifloxacin DRUG

400mg oral pill given once

Moxifloxacin

Placebo DRUG

Placebo oral pill given once

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects between 18 and 50 years of age and with a body mass index ≥ 18 to ≤ 33 kg/m2, and weight of ≥ 40 to ≤ 100 kg inclusive.
• Subject is in good health as judged by the investigator based on the laboratory criteria and no clinically significant findings on the medical history or physical examination.
• Females of child-bearing potential (defined as less than one year post-menopause) are eligible for enrollment if they are not breast feeding, they have a negative serum pregnancy test before study entry, and they are using a highly effective method of contraception for at least 3 months before study drug administration, during the study, and for at least 6 months after study completion.
• Subjects who are willing to comply with all study activities and procedures and have provided written informed consent prior to any study procedures and have signed and dated a Health Insurance Portability and Accountability Act (HIPAA) authorization form.

You may not qualify if:

• A history of additional risk factors for TdP.
• Unstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia.
• Sustained supine systolic blood pressure \>150 mmHg, or \<110 mmHg in Part 1 or \<100mmHg in Part 2, or a diastolic blood pressure \>95 mmHg at screening or baseline.
• A resting pulse rate at rest, taken during screening, of \<40 bpm or \>100 bpm.
• An abnormal screening ECG indicating a second- or third-degree atrioventricular (AV) block, or one or more of the following: QRS \>110 milliseconds (msec), QTcB \>470 msec for females or 450 msec for males, PR interval \>240 msec, or any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant.
• Uncontrolled hypertension, asthma, unstable diabetes (type I or type II), thyroid disease, seizures, myasthenia gravis, or any other neuromuscular disorder.
• Positive results at screening for hepatitis B virus, hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection.
• History of central nervous system disorders, epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).
• The subject has a history of any cancer, except basal cell or stage 1 squamous cell carcinoma of the skin, which has not been in remission for at least 5 years prior to the first dose of study drug.
• Subjects who have any condition possibly affecting drug absorption.
• History of significant hearing loss or a family history of hearing loss, excluding age related (≥ age 65) hearing loss. A prior diagnosis of sensorineural hearing loss or Ménière's disease.
• Clinically significant illness, including viral syndromes within 3 weeks of dosing.
• The use of concomitant medications that prolong the QT/QTc interval.
• Used prescription medications, over-the-counter (OTC) medications, investigational medications/therapy, vitamins, or nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff, etc.) within 28 days or 5 half-lives, whichever is longer, before dosing of ACHN-490 Injection.
• Used aminoglycosides within 6 months prior to IMP administration.

Sponsors & Collaborators

• Achaogen, Inc.: lead
• Department of Health and Human Services: collaborator

Study Sites (1)

Investigational Site

West Bend, Wisconsin, 53095, United States

Location

Related Publications (1)

• Gall J, Choi T, Riddle V, Van Wart S, Gibbons JA, Seroogy J. A Phase 1 Study of Intravenous Plazomicin in Healthy Adults to Assess Potential Effects on the QT/QTc Interval, Safety, and Pharmacokinetics. Clin Pharmacol Drug Dev. 2019 Nov;8(8):1032-1041. doi: 10.1002/cpdd.653. Epub 2019 Jan 16.

  PMID: 30650259 DERIVED

MeSH Terms

Interventions

plazomicin; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Achaogen, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: January 23, 2012
• Study Start: October 1, 2011
• Study Completion: March 1, 2012
• Last Updated: May 9, 2012

Record last verified: 2012-05

Locations

US (1)