Evaluation of Celecoxib Effects on Amlodipine in Subjects With Existing Hypertension Requiring Antihypertensives

This was a multi-center, randomized, double blind, placebo controlled study to evaluate the effect of celecoxib on the efficacy, safety, and pharmacokinetics of amlodipine in subjects with existing hypertension requiring antihypertensive therapy. Approximately 105 eligible subjects were to be randomized 3:3:1 to one of three treatment arms.

Arm 1:OE 10 mg Norvasc tablet+OE 200 mg Celebrex capsule (amlodipine+celecoxib arm)

Arm 2:OE 10 mg Norvasc tablet+matched placebo for OE Celebrex capsule (amlodipine+placebo arm)

Arm 3:Matched placebo for OE Norvasc tablet+matched placebo for OE Celebrex capsule (placebo+placebo arm).

Following an up to 14-day screening phase, eligible subjects were randomized to one of the 3 treatment arms. All drugs were to be administered orally qd for 14 days for a total of 14 doses. Visits at the clinic took place at the start and at the end of the screening phase, at Study Day 0 (start of treatment), Day 6, Day 7, Day 13 (end of treatment), Day 14 and Day 28 (end of follow-up).

Inclusion criteria

• Adult 40 to 75 years of age
• Existing hypertension that is being treated using pharmacological therapy with a single agent that is not a calcium channel blocker
• SBPday > 135 and ≤ 169 mmHg and average daytime (9:00 to 21:00) ambulatory diastolic blood pressure (DBPday) ≤ 110 mmHg at Day 0 (after the 10- to 14-day washout from prior blood pressure medication)
• Body Mass Index of 18.5 to 34.9 kg/m2
• Healthy (other than hypertension) as determined by the Investigator based on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests
• A negative pregnancy test at initial screening visit
• If woman of childbearing potential, agree to use a highly effective form of birth control while on study (from Screening through final study visit)
• Able to comprehend and sign an informed consent form.

Exclusion criteria

• Resting SBP > 169 mmHg or a resting DBP > 110 mmHg at initial screening visit while on their standard antihypertensive therapy (where resting is defined as supine for at least 10 minutes with minimal interaction)
• Weight < 55 kg
• Fragile health
• Evidence of clinically significant findings on screening evaluations (clinical, laboratory, and ECG) which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of safety data
• Current or recent history (within four weeks prior to initial screening visit) of a clinically significant bacterial, fungal, or mycobacterial infection
• Current clinically significant viral infection
• History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin
• Major surgery within four weeks prior to initial screening visit
• Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's disease or chronic pancreatitis)
• Active peptic ulceration or history of gastrointestinal bleeding
• History of myocardial infarction, congestive heart failure, or stroke
• Any current cardiovascular disease (other than hypertension)
• History of psychotic disorder
• History of alcoholism or drug addiction or current alcohol or drug use that, in the opinion of the Investigator, will interfere with the subject's ability to comply with the dosing schedule and study evaluations
• History of any illicit drug use within one year prior to initial screening visit
• Positive drug screen at initial screening visit. A positive drug screen for opiates only (with all other drug tests negative) will not be a basis for exclusion if the subject took over-the-counter narcotics as indicated on the product label within 24 hours prior to the drug screen
• Current treatment or treatment within 30 days prior to first dose of study drugs with another investigational drug or current enrollment in another clinical trial
• Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Known hypersensitivity to amlodipine or celecoxib
• Known hypersensitivity to the inactive ingredients in the over-encapsulated (OE) study drugs
• Asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic type reactions after taking acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors
• Subjects who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule and study evaluations
• Pregnant or lactating
• Unable to correctly use ambulatory blood pressure monitor after instruction on its use
• Subjects with Child-Pugh Class B or C cirrhosis
• Subjects currently taking a calcium channel blocker or any NSAID for any reason will be excluded. Subjects will not be withdrawn from these drugs to be enrolled in the trial
• Subjects that took a calcium channel blocker in the past for any indication
• Creatinine clearance < 50 ml/min as estimated by the Cockroft-Gault equation
• Known cytochrome P450 2C9 poor metabolizer
• Subjects with allergy or hypersensitivity to sulfonamides