Open-Labeled PK-PD Studies of Metoprolol ER

NCT ID: NCT02417246

Last Updated: 2020-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2018-06-06

Brief 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.

Detailed Description

As a participant in this study the following will happen.

A study nurse will draw 3 teaspoonfuls (15 ml) of blood. Two teaspoons (10ml) will be drawn for basic blood work and one teaspoon (5ml) will be drawn for genotyping. The study physician will perform a physical exam and discuss all medical history.

The study will be randomized to one of two groups like flipping a coin.

• Study Sequence A- start with brand name metoprolol ER, switch to Generic B metoprolol, switch back to brand name metoprolol ER, then switch to Generic A metoprolol
• Study Sequence B- start with brand name metoprolol ER, switch to Generic A metoprolol, switch back to brand name metoprolol ER, then switch to Generic B metoprolol.

Each study sequence will consist of treatment with brand name metoprolol ER for 2 periods, treatment with Generic A metoprolol ER for one period, and treatment with Generic B metoprolol ER for one period. The generic drug periods will be in a different order for each study group. During the times the switch will take place the following tests will be performed: 24-hour pharmacokinetic parameter assessment, 24-hour heart rate monitoring, 24-hour blood pressure monitoring, 24-hour holter monitoring, exercise treadmill to induce heart rate, and a 24-hour gastric potential hydrogen (pH) monitoring via a wireless capsule.

Conditions

Blood Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Study Sequence A

Start with brand name metoprolol ER, switch to Generic B metoprolol, switch back to brand name metoprolol ER, then switch to Generic A metoprolol

Group Type: ACTIVE_COMPARATOR

brand name metoprolol ER

Intervention Type: DRUG

This medication will be taken for 7 to 28 days

Generic A

Intervention Type: DRUG

This medication will be taken for 7 days

Generic B

Intervention Type: DRUG

This medication will be taken for 7 days

Study Sequence B

Start with brand name metoprolol ER, switch to Generic A metoprolol, switch back to brand name metoprolol ER, then switch to Generic B metoprolol.

Group Type: ACTIVE_COMPARATOR

brand name metoprolol ER

Intervention Type: DRUG

This medication will be taken for 7 to 28 days

Generic A

Intervention Type: DRUG

This medication will be taken for 7 days

Generic B

Intervention Type: DRUG

This medication will be taken for 7 days

Interventions

brand name metoprolol ER

This medication will be taken for 7 to 28 days

Intervention Type: DRUG

Generic A

This medication will be taken for 7 days

Intervention Type: DRUG

Generic B

This medication will be taken for 7 days

Intervention Type: DRUG

Other Intervention Names

Metoprolol extended-release (ER); Metoprolol extended-release (ER); Metoprolol extended-release (ER)

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Larisa Cavallari, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Family Medicine at Hampton Oaks Medical Plaza

Gainesville, Florida, United States

Oak Hammock at the University of Florida

Gainesville, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

FD14-024

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OCR15985

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201500092

Identifier Type: -

Identifier Source: org_study_id