Inclusion criteria:

• Adult males or females of non-child bearing potential who are between 18 and 60 years old.
• Have a history of mild to moderate essential hypertension or present with mild to moderate essential hypertension defined by Diastolic Blood Pressure >/90 and </109 mmHg, and/or Systolic Blood Pressure >/140 and </179 mmHg
• Body weight > 60 kg (132 pounds) and body mass index (BMI) between 19 and 35

Exclusion criteria:

• Any clinically relevant abnormality identified on the screening history, physical or laboratory examination, or any other medical condition or circumstances making the volunteer unsuitable for participation in the study.
• History of advanced retinopathy (i.e., Keith-Wagener Grade III or IV)
• Secondary forms of hypertension including (but not limited to) coarctation of the aorta, primary aldosteronism, renal artery stenosis, or pheochromocytoma
• Type 1 diabetics [note: Type 2 diabetics with HgbA1c less than or equal to 9.0% can be enrolled provided the Investigator considers the subject clinically stable]
• Signs, symptoms, or history of congestive heart failure, angina pectoris, myocardial infarction, cerebrovascular accident, or transient ischemic attacks
• History or presence of clinically significant hepatic disease
• Liver function tests (ALT, AST, total bilirubin or alkaline phosphatase) more than 2 times the upper limit of the laboratory reference range
• History of severe pulmonary disease including asthma or chronic obstructive lung disease or previous history of 'hypersensitivity' to B-blockers
• Previously treated hypertension in subjects in whom, at the discretion of the Investigator, antihypertensive therapy cannot be safely withdrawn during the study
• Subjects who are on more than 3 antihypertensive or diuretic medications [Note: combination antihypertensive and/or diuretic products (such as lisinopril and hydrochlorothiazide) should be considered as 2 medications, and the doses of each component should be recorded.]
• Subjects who metabolize carvedilol poorly based on CYP2D6 genotyping as determined at screening
• History of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening
• Positive urine drug screen (UDS) including alcohol at screening. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• Treatment with an investigational drug within 30 days or five half-lives, whichever is longer, prior to the first dose of study medication (this includes investigational formulations of marketed products)

• Subjects receiving ongoing treatment or anticipated to receive treatment with any of the following medications during treatment with study medication:

  • monoamine oxidase (MAO) inhibitors
  • any Class I or III antiarrhythmic
  • alpha-adrenergic receptor blockers
  • beta-2-adrenergic receptor agonists
  • lithium
• Consumption of grapefruit or grapefruit juice within 7 days prior to dosing
• Women of child-bearing potential
• NOTE: Pre-menopausal females with a documented tubal ligation or hysterectomy are eligible. Postmenopausal females are eligible, defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].
• Resting pulse rate of ≤ 50 beats per minute (bpm) at screening
• QTc ≥ 450 msec
• ECG criteria as defined in protocol
• Refusal or inability to discontinue use of medications known to be inhibitors/inducers of cytochrome P-450 2C9, 2D6 and 3A4 for at least 14 days or 5 half-lives [which ever is longer] prior to Day 1 of Session 1 and until 48 hours after the last dose of study medication. [Examples include: paroxetine, isoniazid, "azole"antifungal drugs (e.g. itraconazole), erythromycin, ticlopidine, amiodarone, quinidine, rifampin, phenobarbital]
• Donation of blood in excess of 500 mL within a 56-day period including the estimated 210 mL of blood to be drawn during this study
• History of sensitivity to carvedilol, lisinopril, alpha-blockers, beta-blockers or ACE inhibitors
• History of sensitivity to heparin, heparin-induced thrombocytopenia, or sensitivity to any of the study medications or components thereof
• History of angioedema
• Positive for Hepatitis B surface antigen
• Positive for HIV
• Unwillingness or inability to follow the procedures outlined in the protocol or inability to provide written informed consent