A Safety Evaluation of ECG Intervals and Blood Pressure in Normal Healthy Volunteers After Use of Nebivolol, Atenolol, Moxifloxacin, or Placebo

A Randomized, Parallel Group Safety Evaluation of Electrocardiographic Intervals and Blood Pressure in Normal Healthy Volunteers After Nebivolol, Atenolol, Moxifloxacin, or Placebo Administration After Single and Repeated Doses

Nebivolol is one of a class of drugs known as beta-blockers. These drugs are useful in the treatment of high blood pressure, angina, abnormal heart rhythms and following a heart attack. The purpose of this study is to explore the potential of nebivolol to cause a certain type of abnormal heart rhythm, known as QTc prolongation. The potential of nebivolol to cause this adverse event will be compared to three other drugs: atenolol, a beta-blocker approved by the FDA; Avelox (moxifloxacin), an anti-biotic approved for use by the FDA which is known to cause QTc prolongation; and placebo, a drug look-alike that contains no drug. The working hypothesis was that 20 or 40 mg of nebivolol would not prolong corrected QT intervals measured during peak nebivolol concentrations (i.e., 2 hours after dosing) on Day 7.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Moxifloxacin; Drug: Atenolol; Drug: Nebivolol

• Study Type: Interventional
• Enrollment: 260
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33181
      • SFBC International, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and nonpregnant, nonlactating women were 18 years or older.
• Women declaring postmenopausal or surgical sterility.
• Women of childbearing potential who had a negative serum HCG within 2 weeks of dosing.
• Male subjects weighed at least 60 kg (132 lb), and female subjects weighed at least 48 kg (106 lb). All volunteers weighed within 15% of their ideal body weight (IBW).

Exclusion Criteria:

• Institutionalized

• Reported or was known to have done the following:

  • Used any tobacco product.
  • Ingested any alcoholic, caffeine or xanthine containing food or beverage within the 48 hours prior to the initial dose of study medication
  • Consumed grapefruit or grapefruit containing products within 7 days prior to the initial dose of study medication.
  • Ingested any vitamins or herbal products within the 48 hours prior to the initial dose of study medication.
  • Recently changed dietary or exercise habits significantly
• Used any medication (including over-the-counter [OTC]) within the 14 days prior to the initial dose of study medication.
• Used any medication known to alter hepatic enzyme activity within 28 days prior to the initial dose of study medication.
• Received an investigational drug within 30 days prior to the initial dose of study medication.
• History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic disease.
• History of drug and/or alcohol abuse within 1 year prior to the study.
• Acute illness at the time of either the pre study medical evaluation or dosing.
• Any laboratory results deemed clinically significant by the physician.
• Abnormal and clinically relevant ECG tracing.
• Donated or lost a significant volume of blood or plasma (>450 mL) within 28 days prior to the initial dose of study medication.
• Allergic or hypersensitive to nebivolol, atenolol, or other β blocking drugs or to moxifloxacin or other quinolone antibiotics.
• History of seizures or cerebrovascular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The primary study endpoint was the change in the average QTc intervals from Day 0 to 2 hours after dosing on Day 7.

Secondary Outcome Measures

Outcome Measure
The secondary endpoints were the change in average QTc intervals from Day 0 to all other evaluation times and the change in other ECG intervals (PR, RR, QRS, QT) and HR from Day 0 to all other evaluation times.

Collaborators and Investigators

• Sponsor: Mylan Bertek Pharmaceuticals
• Investigators: Principal Investigator: Lawrence A Galitz, MD, SFBC International; Study Director: Will A Sullivan, BS, Mylan Bertek Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Study Completion: July 1, 2003

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): September 12, 2005
• Last Update Submitted That Met QC Criteria: September 7, 2005
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antineoplastic Agents; Adrenergic Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Moxifloxacin; Nebivolol; Atenolol
• Other Study ID Numbers: NEB122