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

NCT ID: NCT02172040

Last Updated: 2018-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-26
• Study Completion Date: 2015-11-19

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."

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Amlodipine+Celecoxib

Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks

Group Type: EXPERIMENTAL

Over-encapsulated 10 mg amlodipine besylate tablet

Intervention Type: DRUG

Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks

Over-encapsulated 200 mg celecoxib capsule

Intervention Type: DRUG

Over-encapsulated 200 mg celecoxib capsule once a day for two weeks

Amlodipine+Placebo

Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks

Group Type: ACTIVE_COMPARATOR

Over-encapsulated 10 mg amlodipine besylate tablet

Intervention Type: DRUG

Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks

Matched placebo capsule for over-encapsulated celecoxib capsule

Intervention Type: DRUG

Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks

Placebo+Celecoxib

Matched placebo capsule for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks

Group Type: PLACEBO_COMPARATOR

Over-encapsulated 200 mg celecoxib capsule

Intervention Type: DRUG

Over-encapsulated 200 mg celecoxib capsule once a day for two weeks

Matched placebo capsule for over-encapsulated amlodipine besylate tablet

Intervention Type: DRUG

Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks

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

Group Type: SHAM_COMPARATOR

Matched placebo capsule for over-encapsulated celecoxib capsule

Intervention Type: DRUG

Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks

Matched placebo capsule for over-encapsulated amlodipine besylate tablet

Intervention Type: DRUG

Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks

Interventions

Over-encapsulated 10 mg amlodipine besylate tablet

Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks

Intervention Type: DRUG

Matched placebo capsule for over-encapsulated celecoxib capsule

Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks

Intervention Type: DRUG

Over-encapsulated 200 mg celecoxib capsule

Over-encapsulated 200 mg celecoxib capsule once a day for two weeks

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Norvasc; Placebo; Celebrex; Placebo

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kitov Pharmaceuticals, Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J. Paul Waymack, MD, ScD

Role: STUDY_DIRECTOR

Kitov Pharma Ltd

Brendan Colgan, MD

Role: PRINCIPAL_INVESTIGATOR

Celerion

Claire Kightley, MB

Role: PRINCIPAL_INVESTIGATOR

Reading Clinical Research Aspect

David Collier, MBBS, PhD, BSc

Role: PRINCIPAL_INVESTIGATOR

Barts Health NHS Trust, William Harvey Heart Centre, Barts & The London, Queen Mary School of Medicine and Dentistry, Queen Mary, University of London

Paul Ivan, MBBS

Role: PRINCIPAL_INVESTIGATOR

Synexus Merseyside Clinical Research Centre

Veronika Horvathova, MD

Role: PRINCIPAL_INVESTIGATOR

Synexus Scotland Clinical Research Centre

Amit Mathew, MS, MBBS

Role: PRINCIPAL_INVESTIGATOR

Synexus Midlands Clinical Research Centre

Alexander Thompson, MB, BS, DRCOG

Role: PRINCIPAL_INVESTIGATOR

Reading Clinical Research Aspect

Mohamed Okily, MB

Role: PRINCIPAL_INVESTIGATOR

Synexus Manchester Clinical Research Centre

Richard Gaunt, MB, ChB, MRCGP, DRCOG

Role: PRINCIPAL_INVESTIGATOR

Rowden Surgery

Patrick Eavis, MBBS, DRCOG, DFFP, MRCGP

Role: PRINCIPAL_INVESTIGATOR

Oldfield Surgery

Arjun Ravi, MBBS, MRCP

Role: PRINCIPAL_INVESTIGATOR

The Medicines Evaluation Unit Ltd.

Locations

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

Countries

United Kingdom

Other Identifiers

2013-005381-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KIT-302-03-01

Identifier Type: -

Identifier Source: org_study_id