Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Over-encapsulated 10 mg amlodipine besylate tablet; Matched placebo capsule for over-encapsulated celecoxib capsule; Over-encapsulated 200 mg celecoxib capsule; Matched placebo capsule for over-encapsulated amlodipine besylate tablet
Intervention description: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks; Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks; Over-encapsulated 200 mg celecoxib capsule once a day for two weeks; Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks
Intervention MeSH terms: Celecoxib; Amlodipine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 152.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: High blood pressure; Systolic blood pressure; Diastolic blood pressure; Antihypertensive

Summary:

      The purpose of this study was to evaluate the effect of celecoxib on the efficacy and safety
      of amlodipine besylate in subjects with newly diagnosed hypertension requiring
      antihypertensive therapy.

      This study was conducted to support a future marketing application for KIT-302. Kitov Pharma
      Ltd. (Kitov) is developing KIT-302, an oral fixed combination drug product (FCDP) consisting
      of the calcium channel blocker amlodipine besylate and the nonsteroidal anti-inflammatory
      drug (NSAID) celecoxib, as a "convenience reformulation" FCDP to facilitate and improve
      patient compliance with the once a day (qd) administration of its individual components,
      amlodipine and celecoxib.

      The formulation of KIT-302 consists of amlodipine besylate and celecoxib co-formulated in a
      single immediate release tablet. However, for this study, two separate capsules were
      utilized: one containing a commercial celecoxib capsule (Celebrex®) or matched placebo
      capsule and one containing a commercial amlodipine besylate tablet (Norvasc®) or matched
      placebo tablet.

      The study hypothesis was that treatment with the amlodipine besylate containing capsule plus
      the celecoxib containing capsule would reduce blood pressure (BP) in subjects with
      hypertension with an efficacy that is not substantially inferior to the effect of amlodipine
      besylate alone (i.e., the amlodipine containing capsule plus the matched placebo for the
      celecoxib capsule).

      The United States (US) Food and Drug Administration (FDA) recently approved KIT-302, under
      the brand name Consensi® (amlodipine and celecoxib) tablets [New Drug Application (NDA)
      210045] for the following indication: "patients for whom treatment with amlodipine for
      hypertension and celecoxib for osteoarthritis are appropriate. Lowering blood pressure
      reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and
      myocardial infarctions."
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult 40 to 75 years of age

          2. Newly diagnosed hypertension that requires chronic pharmacological therapy.
             Specifically, the subject must meet both of the following criteria:

               1. Resting systolic BP ≥140 mmHg and ≤179 mmHg (where resting is defined as supine
                  for at least 10 minutes with minimal interaction) at Initial Screening Visit

               2. SBPday >135 mmHg at Baseline Visit (Day 0)

          3. Body Mass Index of 18.5 to 34.9 kg/m2

          4. 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

          5. A negative pregnancy test at Screening

          6. Both males and women of child bearing potential agree to use adequate contraceptive
             methods while on study (from Screening through final study visit)

          7. Able to comprehend and sign an informed consent form

        Exclusion Criteria:

          1. Resting systolic BP >179 mmHg or a resting diastolic BP >110 mmHg at Screening (where
             resting is defined as supine for at least 10 minutes with minimal interaction) or
             SBP24h >169 mmHg or DBP24h >110 mmHg at randomization

          2. SBPday ≤135 mmHg at baseline (Day 0)

          3. Weight <55 kg

          4. Fragile health

          5. 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

          6. Current or recent history (within 4 weeks prior to Screening) of a clinically
             significant bacterial, fungal, or mycobacterial infection

          7. Current clinically significant viral infection

          8. History of malignancy, with the exception of cured basal cell or squamous cell
             carcinoma of the skin

          9. Major surgery within 4 weeks prior to Screening

         10. Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's
             disease or chronic pancreatitis)

         11. Active peptic ulceration or history of gastrointestinal bleeding

         12. History of myocardial infarction, congestive heart failure, or stroke

         13. Any current cardiovascular disease

         14. History of psychotic disorder

         15. 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

         16. History of any illicit drug use within one year prior to Screening

         17. Positive drug screen at Screening. 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

         18. 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

         19. Current treatment or treatment within 30 days prior to first dose of study drugs with
             an NSAID or systemic corticosteroid

         20. Known history of human immunodeficiency virus, hepatitis B, or hepatitis C

         21. Known hypersensitivity to amlodipine or celecoxib

         22. Known hypersensitivity to the inactive ingredients in the over-encapsulated study
             drugs

         23. Asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other
             allergic type reactions after taking acetylsalicylic acid or NSAIDs including
             cyclooxygenase-2 inhibitors

         24. Subjects who, in the opinion of the Investigator, are unable or unlikely to comply
             with the dosing schedule and study evaluations

         25. Pregnant or lactating

         26. Unable to correctly use ambulatory blood pressure monitor after instruction on its use

         27. Subjects with Child-Pugh Class B or C cirrhosis;

         28. Subjects currently taking a calcium channel blocker for any reason including angina.
             Subjects will not be withdrawn from these drugs to be enrolled in the trial

         29. Creatinine clearance <50 ml/min as estimated by the Cockroft-Gault equation

         30. Known cytochrome P450 2C9 poor metabolizer

         31. Subjects with allergy or hypersensitivity to sulfonamides