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."
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
152
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
Celerion
Belfast, Antrim, United Kingdom
The Medicines Evaluation Unit Ltd.
Manchester, Greater Manchester, United Kingdom
Reading Clinical Research Aspect
Ledbury, Herefordshire, United Kingdom
Synexus Merseyside Clinical Research Centre
Liverpool, Merseyside, United Kingdom
Oldfield Surgery
Bath, North East Somerset, United Kingdom
Rowden Surgery
Chippenham, Wiltshire, United Kingdom
Synexus Midlands Clinical Research Centre
Birmingham, United Kingdom
Synexus Scotland Clinical Research Centre
Glasgow, United Kingdom
Barts Health NHS Trust, William Harvey Heart Centre, Barts & The London, Queen Mary School of Medicine and Dentistry, Queen Mary, University of London
London, United Kingdom
Reading Clinical Research Aspect
Reading, United Kingdom
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint
Time frame: Baseline and 2 weeks
Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk)
Including any untoward medical occurrence in a participant administered study drug, which do not necessarily have a causal relationship with the study drug \[i.e., any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug\].
Time frame: 1 month
Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h)
Time frame: Baseline and 2 weeks
Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight)
Time frame: Baseline and 2 weeks
Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h)
Time frame: Baseline and 2 weeks
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday)
Time frame: Baseline and 2 weeks
Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight)
Time frame: Baseline and 2 weeks
Mean Non-transformed Amlodipine Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Mean Non-transformed Celecoxib Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Mean Log-transformed Amlodipine Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Mean Log-transformed Celecoxib Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint
Time frame: Baseline and 2 weeks
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