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

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ClinicalTrials.gov Identifier: NCT02979197
Recruitment Status : Completed
First Posted : December 1, 2016
Last Update Posted : August 2, 2017
Sponsor:
Information provided by (Responsible Party):
Kitov Pharma Ltd

Brief Summary:

The purpose of this study is to evaluate the effect of celecoxib on the efficacy and safety of amlodipine on renal and vascular function in subjects with existing hypertension requiring antihypertensive therapy.

Kitov Pharmaceuticals, Ltd. (Kitov) is developing KIT-302, an oral fixed combination drug product (FCDP) consisting of the antihypertensive drug amlodipine besylate and the non-steroidal anti-inflammatory drug (NSAID) celecoxib.

KIT-302 is being developed 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, when used together for the treatment of hypertension, to lower blood pressure, in patients who also require the use of an NSAID for relief of the signs and symptoms of osteoarthritis. It is also intended to provide prescribers with detailed data on how the combination affects the antihypertensive effect of the calcium channel blocker.

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 will be 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.

Kitov recently 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) is being conducted to quantify the beneficial renovascular effects noted in the prior study in subjects with existing hypertension requiring antihypertensive therapy.


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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Factorial 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 on Renal and Vascular Function in Subjects With Existing Hypertension Requiring Antihypertensive Therapy
Study Start Date : November 2016
Actual Primary Completion Date : July 21, 2017
Actual Study Completion Date : July 21, 2017

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 qd for 14 days
Drug: Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule
Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule qd for 14 days
Other Names:
  • Norvasc
  • Celebrex

Active Comparator: Amlodipine+Placebo
Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule qd for 14 days
Drug: Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule
Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule qd for 14 days
Other Name: Norvasc

Sham Comparator: Placebo+Placebo
Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule qd for 14 days
Drug: Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule qd for 14 days
Other Name: Placebo




Primary Outcome Measures :
  1. Mean reduction in average daytime (9:00 to 21:00) ambulatory systolic blood pressure (SBPday) [ Time Frame: Baseline and 14 days ]

Secondary Outcome Measures :
  1. Mean change in body weight [ Time Frame: Baseline and 14 days ]
  2. Mean reduction in average 24-hour ambulatory systolic blood pressure (SBP24h) [ Time Frame: Baseline and 14 days ]
  3. Mean reduction in average 24-hour ambulatory diastolic blood pressure (DBP24h) [ Time Frame: Baseline and 14 days ]
  4. Mean change in creatinine clearance [ Time Frame: Baseline and 14 days ]
  5. Incidence of treatment emergent adverse events [ Time Frame: 1 month ]
  6. Plasma concentration of amlodipine [ Time Frame: 24 hours post-dose on Day 14 ]


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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. Existing hypertension that is being treated using pharmacological therapy with a single agent that is not a calcium channel blocker
  3. 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)
  4. Body Mass Index of 18.5 to 34.9 kg/m2
  5. 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
  6. A negative pregnancy test at initial screening visit
  7. If woman of childbearing potential, agree to use a highly effective form of birth control while on study (from Screening through final study visit)
  8. Able to comprehend and sign an informed consent form.

Exclusion Criteria:

  1. 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)
  2. Weight < 55 kg
  3. Fragile health
  4. 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
  5. Current or recent history (within four weeks prior to initial screening visit) of a clinically significant bacterial, fungal, or mycobacterial infection
  6. Current clinically significant viral infection
  7. History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin
  8. Major surgery within four weeks prior to initial screening visit
  9. Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's disease or chronic pancreatitis)
  10. Active peptic ulceration or history of gastrointestinal bleeding
  11. History of myocardial infarction, congestive heart failure, or stroke
  12. Any current cardiovascular disease (other than hypertension)
  13. History of psychotic disorder
  14. 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
  15. History of any illicit drug use within one year prior to initial screening visit
  16. 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
  17. 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
  18. Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  19. Known hypersensitivity to amlodipine or celecoxib
  20. Known hypersensitivity to the inactive ingredients in the over-encapsulated (OE) study drugs
  21. Asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic type reactions after taking acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors
  22. Subjects who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule and study evaluations
  23. Pregnant or lactating
  24. Unable to correctly use ambulatory blood pressure monitor after instruction on its use
  25. Subjects with Child-Pugh Class B or C cirrhosis
  26. 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
  27. Subjects that took a calcium channel blocker in the past for any indication
  28. Creatinine clearance < 50 ml/min as estimated by the Cockroft-Gault equation
  29. Known cytochrome P450 2C9 poor metabolizer
  30. 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): NCT02979197


Locations
United Kingdom
Oldfield Surgery
Bath, United Kingdom, BA2 3HT
Celerion
Belfast, United Kingdom, BT9 6AD
Hathaway Medical Centre
Chippenham, United Kingdom, SN14 8GT
Rowden Surgery
Chippenham, United Kingdom, SN15 2SB
Barts Health NHS Trust, Barts Queen Mary University of London, William Harvey Heart Centre
London, United Kingdom, EC1M 6BQ
Medicines Evaluation Unit Ltd.
Manchester, United Kingdom, M23 9QZ
St Chad's Surgery
Radstock, United Kingdom, BA3 2UH
Bradford Road Medical Centre
Trowbridge, United Kingdom, BA1 49AR
Adcroft Surgery
Trowbridge, United Kingdom, BA14 8QA
Sponsors and Collaborators
Kitov Pharma Ltd
Investigators
Study Director: J. Paul Waymack, MD, PhD Kitov Pharma Ltd

Responsible Party: Kitov Pharma Ltd
ClinicalTrials.gov Identifier: NCT02979197     History of Changes
Other Study ID Numbers: KIT-302-03-02
2016-002214-47 ( EudraCT Number )
First Posted: December 1, 2016    Key Record Dates
Last Update Posted: August 2, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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