Evaluation of Celecoxib Effects on Amlodipine in Subjects With Existing Hypertension Requiring Antihypertensives
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study was to evaluate the effect of celecoxib on the efficacy and safety
      of amlodipine besylate on renal and vascular function in subjects with existing hypertension
      requiring antihypertensive therapy.

      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 (KIT-302-03-02), commercial
      celecoxib capsules (Celebrex®) and commercial amlodipine besylate tablets (Norvasc®) were
      separately over-encapsulated (OE) and matched placebos were used to allow for blinding.

      Kitov completed a phase 3 pivotal trial in subjects with newly diagnosed hypertension
      (KIT-302-03-01) demonstrating that the amlodipine + celecoxib combination was statistically
      non-inferior to amlodipine monotherapy with regard to reduction of blood pressure. Further,
      trends towards superior blood pressure lowering effects and improved renal function were
      observed for the combination. This study (KIT-302-03-02) was conducted to quantify the
      beneficial renovascular effects noted in the prior study in subjects with existing
      hypertension requiring antihypertensive therapy.

      On May 31, 2018, the United States (US) Food and Drug Administration (FDA) 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."
    

Detailed description: 
      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).
    

Intervention name(s): OE 10 mg amlodipine besylate tablet; OE 200 mg celecoxib capsule; Matched placebo for OE amlodipine besylate tablet; Matched placebo for OE celecoxib capsule
Intervention type(s): Drug; Drug; Drug; Drug
Other intervention name(s): OE 10 mg Norvasc tablet; OE 200 mg Celebrex capsule; Matched placebo for OE Norvasc tablet; Matched placebo for OE Celebrex capsule
Intervention MeSH terms: Celecoxib; Amlodipine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: High blood pressure; Systolic blood pressure; Diastolic blood pressure; Antihypertensive