Cardiac Effects in Normal Healthy VolunteersPhase 1NCT01514929

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

A Phase 1 study testing ACHN-490 Injection and Moxifloxacin in people with Cardiac Effects in Normal Healthy Volunteers, run by Achaogen, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Cardiac Effects in Normal Healthy Volunteers
What is being tested?: ACHN-490 Injection and Moxifloxacin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 64 participants
Where: 1 siteUnited States
Study dates: Oct 2011to Mar 2012
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

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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.
Used herbal preparations including St. John's wort, ginseng, kava kava, ginkgo biloba, melatonin, and other nutraceuticals within 28 days prior to IMP administration.
Consumed caffeine- or xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.), Seville oranges (sour), grapefruit, grapefruit juice, or fish liver oils within 72 hours prior to IMP administration.
Current participation in a clinical study of an investigational product.
Consumed more than 28 units of ethanol per week at any time in the 6 months before dosing (1 unit of ethanol is equivalent to 8 ounces of beer, 4 ounces of wine, or 1 ounce of spirits) or history of alcoholism and/or drug/chemical abuse. Also, consumption of any amount of ethanol within 72 hours of ACHN-490 Injection dosing.
Donated blood or blood components within 60 days prior to receiving study drug.
Women who are pregnant (or planning to become pregnant within the next 3 months) or currently breastfeeding.
Previous participation in this or any other ACHN-490 Injection study.
Known hypersensitivity to aminoglycosides or any component of the ACHN-490 Injection.
Subjects with poor venous access.
Unable to understand verbal or written English or any other language for which a certified translation of the informed consent is not available.
Any other medical, psychological, or social condition which, in the opinion of the PI or the medical monitor, would prevent the subject from fully participating in the study would represent a concern for study compliance or would constitute a safety concern to the subject.
An employee of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or investigator.
* (Part 1 only) * Acceptable and reproducible spirometry measurements defined as: forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 80% of predicted or FEV1/FVC ratio <70% of predicted. See Appendix 7 for definitions of acceptability and reproducibility.
* (Part 2 only) * Known hypersensitivity to moxifloxacin or other quinolones.
* (Part 2 only) * Taken antacids, sucralfate, multivitamins, or other products with multivalent cations within 8 hours before oral dose in Part 2 or need to take any of the above within 4 hours after the dose administration.
* (Part 2 only) * Taken warfarin or Class IA or Class III antiarrhythmics within one week prior to study drug administration or expected to need to take any of the above during the study period.
* (Part 2 only) * Participation in Part 1 of the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Investigational Site
West Bend, Wisconsin, 53095

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo and Positive-Controlled, Crossover Study to Evaluate the Effect of IV ACHN-490 Injection on the QT/QTc Interval in Healthy Volunteers

Conditions: Cardiac Effects in Normal Healthy Volunteers
Being tested: ACHN-490 Injection, Moxifloxacin, Placebo
Keywords: Thorough QT

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ACHN-490 InjectionDrug
20mg/kg IV 30 minute infusion given once
ACHN-490 InjectionDrug
15mg/kg IV 30 minute infusion given once
MoxifloxacinDrug
400mg oral pill given once
PlaceboDrug
Placebo oral pill given once

Study groups in NCT01514929
Study group	Role	What they receive
Supratherapeutic Dose	Experimental	20mg/kg ACHN-490 Injection Receives: Drug: ACHN-490 Injection
Possible Therapeutic Dose	Experimental	15mg/kg ACHN-490 Injection Receives: Drug: ACHN-490 Injection
Moxifloxacin	Active comparator	400mg moxifloxacin Receives: Drug: Moxifloxacin
Placebo	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 24 hours

Secondary outcomes (5)

PK Parameters
The secondary endpoints for Part 1 of this study will include relevant PK parameters such as AUC0-t, AUC0-∞, CLT, Vss, Cmax, Tmax, and t1/2 measured for 24 hours after receiving study drug.
Measured: 24 hours
ECG Parameters
Part 2 of the study will measure the effect of ACHN-490 Injection compared to placebo within 24 hours of study drug administration on heart rate, PR interval, QRS interval, QTcB, uncorrected QT interval, RR intervals, change in ST and T-wave morphology, and categorical change in QTc variables.
Measured: 24 hours
PK Parameters
Part 2 of this study will measure multiple PK parameters such as AUC0-t, AUC0-∞, CLT, Vss, Cmax, Tmax, and t1/2 measured for 24 hours after receiving study drug.
Measured: 24 hours
Correlation between drug concentration and QTc
Part 2 of this study will measure the correlation between the QTc change from baseline and plasma concentrations of ACHN-490 Injection within 24 hours of study drug administration.
Measured: 24 hours
Safety and tolerability
Part 2 of this study will measure safety and tolerability of ACHN-490 Injection including adverse events, incidence and magnitude of clinically significant changes from baseline in clinical laboratory values (hematology, chemistry, and urinalysis) and physical examination; all for up to 44 days after receiving study drug.
Measured: Up to 44 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2011Mar 2012

First posted23 Jan 2012 (estimated)
Study startOct 2011
Study completionMar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cardiac Effects in Normal Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01514929
Sponsor's protocol ID: ACHN-490-006
Status last verified: May 2012
First submitted: 28 Nov 2011
Last updated: 9 May 2012
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 30650259

Study at a glance

From the registry record, last updated by the sponsor on 9 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo and Positive-Controlled, Crossover Study to Evaluate the Effect of IV ACHN-490 Injection on the QT/QTc Interval in Healthy Volunteers
ClinicalTrials.gov ID: NCT01514929
Acronym / sponsor ID: ACHN-490-006
Conditions: Cardiac Effects in Normal Healthy Volunteers
Keywords: Thorough QT
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: Achaogen, Inc.Industry (pharma, biotech, devices)
Collaborators: Department of Health and Human Services
Study start: Oct 2011
Study completion: Mar 2012 (actual)
First posted: 23 Jan 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Supratherapeutic Dose	Experimental	Drug: ACHN-490 Injection20mg/kg ACHN-490 Injection
Possible Therapeutic Dose	Experimental	Drug: ACHN-490 Injection15mg/kg ACHN-490 Injection
Moxifloxacin	Active comparator	Drug: Moxifloxacin400mg moxifloxacin
Placebo	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (32 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ACHN-490 Injection20mg/kg IV 30 minute infusion given once	Drug	Supratherapeutic Dose
ACHN-490 Injection15mg/kg IV 30 minute infusion given once	Drug	Possible Therapeutic Dose
Moxifloxacin400mg oral pill given once	Drug	Moxifloxacin
PlaceboPlacebo oral pill given once	Drug	Placebo

Primary outcome

Safety
Time frame: 1 day
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.
Effect of ACHN-490 Injection on QTcF
Time frame: 24 hours
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.

5 secondary outcomes

PK Parameters
Time frame: 24 hours
ECG Parameters
Time frame: 24 hours
PK Parameters
Time frame: 24 hours
Correlation between drug concentration and QTc
Time frame: 24 hours
Safety and tolerability
Time frame: Up to 44 days

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2012.
Derived from this study: PubMed 30650259Gall 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Achaogen, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ACHN-490 Injection and Moxifloxacin in people with Cardiac Effects in Normal Healthy Volunteers, run by Achaogen, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety (time frame: 1 day). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01514929, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2012.