Evaluation of the Effect of ATX-101 on QT/QTc Intervals

NCT01706679 | Completed Phase 1

• 1 other identifier: ATX-101-11-24
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the effect of maximum therapeutic and supratherapeutic doses of ATX-101 treatment on Fridericia's corrected QT interval (QTcF).

Conditions

Healthy

Keywords

Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• The effect of maximum therapeutic and supratherapeutic doses of ATX-101 treatment on Fridericia's corrected QT interval (QTcF)

  The primary endpoint will be the mean change between time-matched measurements of QTcF for ATX-101 and placebo after baseline adjustment calculating the upper bound of the one-sided 95% confidence interval. A negative TQT study can be claimed if each upper bound of the one-sided 95% CI is below 10 msec.

  2.5 days

Secondary Outcomes (1)

• To evaluate change from placebo and baseline of the maximum therapeutic and supratherapeutic doses of ATX-101 treatment on QT interval corrected for individuals

  2.5 days

Study Arms (4)

Maximum therapeutic dose of ATX-101

ACTIVE COMPARATOR

ATX-101 10 mg/ml

Drug: ATX-101 (10 mg/ml)

Supratherapeutic dose of ATX-101

ACTIVE COMPARATOR

ATX-101 20 mg/ml

Drug: ATX-101 (20 mg/ml)

Moxifloxacin

ACTIVE COMPARATOR

moxifloxacin (400mg)

Drug: Moxifloxacin (400 mg)

Placebo vehicle

PLACEBO COMPARATOR

placebo vehicle (PBS)

Drug: Placebo vehicle (PBS)

Interventions

ATX-101 (10 mg/ml) DRUG

Maximum therapeutic dose of ATX-101

ATX-101 (20 mg/ml) DRUG

Supratherapeutic dose of ATX-101

Moxifloxacin (400 mg) DRUG

Moxifloxacin

Placebo vehicle (PBS) DRUG

Placebo vehicle

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or nonpregnant, nonlactating females who are aged 18 to 65 years (inclusive). Females must have a negative serum human chorionic gonadotropin (hCG) test result from a sample obtained during the screening period and after admission to the research facility, but before the dose of study material. Females of postmenopausal status must not have had menses for at least one year and if younger than 55 years of age must have a serum FSH level ≥ 35 mIU/mL. Females of childbearing potential must agree to practice adequate contraception, in the judgment of the investigator, during the course of the trial.
• Body Mass Index (BMI) in the range of 20 - 38 kg/m2 (inclusive). Refer to Appendix A.
• Presence of sufficient submental fat into which 25 subcutaneous injections spaced on a 1.0-cm grid can be safely administered based on the investigator's judgment.
• Normal vital signs after 10 minutes resting in a supine position:
• Systolic Blood Pressure: 90 mm Hg to 140 mm Hg
• Diastolic Blood Pressure: 45 mm Hg to 90 mm Hg
• Heart Rate: 45 bpm to 100 bpm
• Normal Resting ECG
• PR Interval: 120 msec to 220 msec
• QRS Duration: \< 120 msec
• QTcF Duration: \< 450 msec
• Serum hemoglobin test result of 11.0 g/dL or greater and negative hepatitis B, hepatitis C, and HIV test result within 28 days before the dose of study material.
• Willing and able to comply with and understand the visit schedule and all of the protocol-specified tests and procedures.
• Medically able to undergo the administration of study material as determined by clinical and laboratory evaluations obtained within 28 days before dosing with study material for which the investigator identifies no clinically significant abnormality.
• Signed informed consent obtained before any study-specific procedure is conducted.

You may not qualify if:

• Any prescription medication taken within 14 days (or 5 elimination half-lives, whichever is longer) of Study Day -2, or have taken any over-the-counter medications, including topical medications, herbal or dietary supplements/remedies within 7 days of Study Day 2, or planned concomitant medication while in the study (except for acetaminophen up to 2 g/day and hormonal birth control).
• A history of additional risk factors for Torsade de Pointes (e.g. hypokalemia, history of drowning survival, family history of Long QT Syndrome, family history of Short QT Syndrome, or family history of unexplainable early sudden death).
• Participation in a study of an investigational drug or device within 30 days prior to the baseline ECG.
• Any condition that, in the judgment of the investigator, would place a subject at undue risk, or potentially compromise the results or interpretation of the study.
• Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest \> 100 beats per minute.
• Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
• Subjects not in sinus rhythm at screening.
• Hypersensitivity to Moxifloxacin
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
• Use of tobacco or nicotine-containing products within 3 months prior to dose.
• History of any intervention to treat submental fat (e.g. liposuction, surgery, or lipolytic agents).
• History of trauma associated with the chin or neck areas, which in the judgment of the investigator may affect evaluation of safety of treatment.
• Loose skin in the neck or chin area for which reduction in submental fat may, in the judgment of the investigator, result in a cosmetically unacceptable outcome.
• Prominent platysmal bands at rest that interfere with the evaluation of submental fat.
• Evidence of any cause of enlargement in the submental area other than localized subcutaneous fat.

Sponsors & Collaborators

• Kythera Biopharmaceuticals: lead

Study Sites (1)

Comprehensive Clinical Development

Miramar, Florida, 33027, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Royce Morrison, MD, PhD

  Comprehensive Clinical Development

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2012
• First Posted: October 15, 2012
• Study Start: October 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 14, 2013

Record last verified: 2012-10

Locations

US (1)