Open-Labeled PK-PD Studies of Metoprolol ER
Condition: Blood Pressure
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): brand name metoprolol ER; Generic A; Generic B
Intervention type(s): Drug; Drug; Drug
Intervention description(s): This medication will be taken for 7 to 28 days; This medication will be taken for 7 days; This medication will be taken for 7 days
Other intervention name(s): Metoprolol extended-release (ER); Metoprolol extended-release (ER); Metoprolol extended-release (ER)
Intervention MeSH terms: Metoprolol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: pharmacokinetics; pharmacodynamics; pharmacogenetics