Clinical trial NCT00158093: A Safety Evaluation of ECG Intervals and Blood Pressure in Normal Healthy Volunteers After Use of Nebivolol, Atenolol, Moxifloxacin, or Placebo
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Mylan Bertek Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
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 outcomes:
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.
Other outcomes:
Locations:
city: Miami
country: United States
facility: SFBC International, Inc.
state: Florida
Study officials:
affiliation: SFBC International
name: Lawrence A Galitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mylan Bertek Pharmaceuticals Inc.
name: Will A Sullivan, BS
role: STUDY_DIRECTOR
References: