Open-Labeled PK-PD Studies of Metoprolol ER
| Status: | Active, not recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 120 |
| Updated: | 12/30/2018 |
| Start Date: | August 2015 |
| End Date: | March 2019 |
Open-Labeled Pharmacokinetic and Pharmacodynamic (PK-PD) Studies of Metoprolol ER
Recently, the quality of generic metoprolol extended-release (ER) (Toprol XL,
Activas,Wockhardt) 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 formulation. 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.
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.
Activas,Wockhardt) 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 formulation. 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.
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.
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, Dr. Sigfried Schmidt 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 Group A- start with Toprol XL, switch to Wockhardt metoprolol, switch back to
Toprol XL, then switch to Activas metoprolol
- Study Group B- start with Toprol XL, switch to Activas metoprolol, switch back to Toprol
XL, then switch to Wockhardt metoprolol.
Each study group will consist of treatment with Toprol XL for 2 periods, treatment with
Wockhardt metoprolol for one period, and treatment with Activas metoprolol 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
parameters, 24-hour heart rate, 24-hour blood pressure, 24-hour holter monitor, exercise
treadmill to induced heart rate, and a 24-hour gastric pH through SmartPill Capsule.
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, Dr. Sigfried Schmidt 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 Group A- start with Toprol XL, switch to Wockhardt metoprolol, switch back to
Toprol XL, then switch to Activas metoprolol
- Study Group B- start with Toprol XL, switch to Activas metoprolol, switch back to Toprol
XL, then switch to Wockhardt metoprolol.
Each study group will consist of treatment with Toprol XL for 2 periods, treatment with
Wockhardt metoprolol for one period, and treatment with Activas metoprolol 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
parameters, 24-hour heart rate, 24-hour blood pressure, 24-hour holter monitor, exercise
treadmill to induced heart rate, and a 24-hour gastric pH through SmartPill Capsule.
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 UF
Health Family Medicine clinic
Exclusion Criteria:
- Documented secondary forms of HTN
- 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
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