Open-Labeled PK-PD Studies of Metoprolol ER

• Status: Completed
• Trial end date: 2018-06-06
• Target enrollment: 0
• Participant gender: All

Summary

Recently, the quality of generic metoprolol extended-release (ER) products has been called into question with reports of inconsistent effects when switching from the brand name product to a generic formulation. Problems with how the body processes these drugs could have serious and widespread consequences given the high frequency of metoprolol ER use in the management of various cardiovascular disorders, including high blood pressure, coronary heart disease, heart failure, and cardiac arrhythmias. Investigators hypothesize that both product- and subject-specific factors lead to variability in the way the body breaks down the drug (pharmacokinetics) and clinical response to generic versus name brand metoprolol ER formulations. Investigators will study the brand name and generic metoprolol ER formulations in subjects with high blood pressure to compare the pharmacokinetics and cardiovascular responses among equivalent labeled doses of each product (brand name and two approved generics).

The study objective is to provide information on how the body breaks down generic and brand name metoprolol ER products (pharmacokinetics) and how the body responds to generic and brand name metoprolol ER products (pharmacodynamics) to better understand if generic metoprolol ER products are as good as the brand name product.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Florida
• Collaborator: Food and Drug Administration (FDA)
• Treatments: Metoprolol

Criteria

Inclusion Criteria:

• Subjects will be targeted for enrollment based on current treatment of their hypertension with a beta-blocker or known tolerability to a beta-blocker based on their previous participation in the Pharmacogenomic Evaluation of Antihypertensive Responses studies (PEAR-1 and PEAR-2). If necessary to meet enrollment targets, additional patients will be recruited from the existing patient population in the University of Florida Health Family Medicine clinic or through other means.

Exclusion Criteria:

• Documented secondary forms of hypertension

• Known cardiovascular disease (including history of angina pectoris, myocardial infarction, coronary revascularization procedure, heart failure, or presence of a cardiac pacemaker)

• Known cerebrovascular disease (including stroke and TIA)

• Known peripheral vascular disease

• Diabetes mellitus (Type 1 or 2) (defined as a diabetes diagnosis in the medical record or fasting blood glucose greater than or equal to 126 mg per dl or nonfasting blood glucose greater than or equal to 200 mg per dl on screening laboratories)

• Systolic blood pressure (SBP) greater than180 mm Hg on screening visit

• Heart rate less than 55 bpm on screening visit (in the absence of treatment with a beta-blocker)

• Renal insufficiency (serum creatinine greater than 1.5 in men or greater than 1.4 in women on screening laboratories)

• Liver enzymes (ALT and or AST) greater than 3 times the upper limit of normal on screening laboratories.

• Known Raynaud's phenomenon

• Known asthma or chronic obstructive pulmonary disease

• Pregnancy or lactation

• Gastric bezoar

• Swallowing disorders

• Strictures

• Fistulas

• GI obstruction

• Severe dysphagia

• Crohn's disease

• Diverticulitis

• Any implantable electromedical device

• Use of non-dihydropyridine calcium channel blockers (diltiazem or verapamil)

• Use of digoxin to avoid additive effects on heart rate