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Trial record 2 of 2 for:    kit-302

Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy

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ClinicalTrials.gov Identifier: NCT02172040
Recruitment Status : Completed
First Posted : June 24, 2014
Results First Posted : October 3, 2017
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
Kitov Pharma Ltd

Brief 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."


Condition or disease Intervention/treatment Phase
Hypertension Drug: Over-encapsulated 10 mg amlodipine besylate tablet Drug: Matched placebo capsule for over-encapsulated celecoxib capsule Drug: Over-encapsulated 200 mg celecoxib capsule Drug: Matched placebo capsule for over-encapsulated amlodipine besylate tablet Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective Randomized Placebo Controlled Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy
Actual Study Start Date : June 26, 2014
Actual Primary Completion Date : November 19, 2015
Actual Study Completion Date : November 19, 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Amlodipine+Celecoxib
Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks
Drug: Over-encapsulated 10 mg amlodipine besylate tablet
Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks
Other Name: Norvasc

Drug: Over-encapsulated 200 mg celecoxib capsule
Over-encapsulated 200 mg celecoxib capsule once a day for two weeks
Other Name: Celebrex

Active Comparator: Amlodipine+Placebo
Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
Drug: Over-encapsulated 10 mg amlodipine besylate tablet
Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks
Other Name: Norvasc

Drug: Matched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
Other Name: Placebo

Placebo Comparator: Placebo+Celecoxib
Matched placebo capsule for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks
Drug: Over-encapsulated 200 mg celecoxib capsule
Over-encapsulated 200 mg celecoxib capsule once a day for two weeks
Other Name: Celebrex

Drug: Matched placebo capsule for over-encapsulated amlodipine besylate tablet
Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks
Other Name: Placebo

Sham Comparator: Placebo+Placebo
Matched placebo capsule for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
Drug: Matched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
Other Name: Placebo

Drug: Matched placebo capsule for over-encapsulated amlodipine besylate tablet
Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks
Other Name: Placebo




Primary Outcome Measures :
  1. Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint [ Time Frame: Baseline and 2 weeks ]
  2. Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk) [ Time Frame: 1 month ]
    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].


Secondary Outcome Measures :
  1. Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) [ Time Frame: Baseline and 2 weeks ]
  2. Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) [ Time Frame: Baseline and 2 weeks ]
  3. Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h) [ Time Frame: Baseline and 2 weeks ]
  4. Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday) [ Time Frame: Baseline and 2 weeks ]
  5. Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight) [ Time Frame: Baseline and 2 weeks ]
  6. Mean Non-transformed Amlodipine Plasma Concentration [ Time Frame: 24 hours post-dose on Day 14 ]
  7. Mean Non-transformed Celecoxib Plasma Concentration [ Time Frame: 24 hours post-dose on Day 14 ]
  8. Mean Log-transformed Amlodipine Plasma Concentration [ Time Frame: 24 hours post-dose on Day 14 ]
  9. Mean Log-transformed Celecoxib Plasma Concentration [ Time Frame: 24 hours post-dose on Day 14 ]
  10. Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint [ Time Frame: Baseline and 2 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02172040


Locations
United Kingdom
Celerion
Belfast, Antrim, United Kingdom, BT9 6AD
The Medicines Evaluation Unit Ltd.
Manchester, Greater Manchester, United Kingdom, M23 9QZ
Reading Clinical Research Aspect
Ledbury, Herefordshire, United Kingdom, HR8 2AA
Synexus Merseyside Clinical Research Centre
Liverpool, Merseyside, United Kingdom, L22 0LG
Oldfield Surgery
Bath, North East Somerset, United Kingdom, BA2 3HT
Rowden Surgery
Chippenham, Wiltshire, United Kingdom, SN15 2SB
Synexus Midlands Clinical Research Centre
Birmingham, United Kingdom, B15 2SQ
Synexus Scotland Clinical Research Centre
Glasgow, United Kingdom, G20 0SP
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, EC1M 6BQ
Reading Clinical Research Aspect
Reading, United Kingdom, RG6 6BZ
Sponsors and Collaborators
Kitov Pharma Ltd
Investigators
Study Director: J. Paul Waymack, MD, ScD Kitov Pharma Ltd
Principal Investigator: Brendan Colgan, MD Celerion
Principal Investigator: Claire Kightley, MB Reading Clinical Research Aspect
Principal Investigator: David Collier, MBBS, PhD, BSc Barts Health NHS Trust, William Harvey Heart Centre, Barts & The London, Queen Mary School of Medicine and Dentistry, Queen Mary, University of London
Principal Investigator: Paul Ivan, MBBS Synexus Merseyside Clinical Research Centre
Principal Investigator: Veronika Horvathova, MD Synexus Scotland Clinical Research Centre
Principal Investigator: Amit Mathew, MS, MBBS Synexus Midlands Clinical Research Centre
Principal Investigator: Alexander Thompson, MB, BS, DRCOG Reading Clinical Research Aspect
Principal Investigator: Mohamed Okily, MB Synexus Manchester Clinical Research Centre
Principal Investigator: Richard Gaunt, MB, ChB, MRCGP, DRCOG Rowden Surgery
Principal Investigator: Patrick Eavis, MBBS, DRCOG, DFFP, MRCGP Oldfield Surgery
Principal Investigator: Arjun Ravi, MBBS, MRCP The Medicines Evaluation Unit Ltd.

Responsible Party: Kitov Pharma Ltd
ClinicalTrials.gov Identifier: NCT02172040     History of Changes
Other Study ID Numbers: KIT-302-03-01
2013-005381-19 ( EudraCT Number )
First Posted: June 24, 2014    Key Record Dates
Results First Posted: October 3, 2017
Last Update Posted: October 10, 2018
Last Verified: September 2018

Keywords provided by Kitov Pharma Ltd:
High blood pressure
Systolic blood pressure
Diastolic blood pressure
Antihypertensive

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Antihypertensive Agents
Celecoxib
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents