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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02172040
• Other study ID #: KIT-302-03-01
• Secondary ID: 2013-005381-19
• Status: Completed
• Phase: Phase 3
• Start date: June 26, 2014
• Est. completion date: November 19, 2015

Study information

• Verified date: September 2018
• Source: Kitov Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: November 19, 2015
• Est. primary completion date: November 19, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Over-encapsulated 10 mg amlodipine besylate tablet
Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks
• Matched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
• Over-encapsulated 200 mg celecoxib capsule
Over-encapsulated 200 mg celecoxib capsule once a day for two weeks
• Matched placebo capsule for over-encapsulated amlodipine besylate tablet
Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks

Locations

Country	Name	City	State
United Kingdom	Oldfield Surgery	Bath	North East Somerset
United Kingdom	Celerion	Belfast	Antrim
United Kingdom	Synexus Midlands Clinical Research Centre	Birmingham
United Kingdom	Rowden Surgery	Chippenham	Wiltshire
United Kingdom	Synexus Scotland Clinical Research Centre	Glasgow
United Kingdom	Reading Clinical Research Aspect	Ledbury	Herefordshire
United Kingdom	Synexus Merseyside Clinical Research Centre	Liverpool	Merseyside
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	The Medicines Evaluation Unit Ltd.	Manchester	Greater Manchester
United Kingdom	Reading Clinical Research Aspect	Reading

Sponsors (1)

Lead Sponsor	Collaborator
Kitov Pharma Ltd

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint		Baseline and 2 weeks
Primary	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].	1 month
Secondary	Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h)		Baseline and 2 weeks
Secondary	Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight)		Baseline and 2 weeks
Secondary	Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h)		Baseline and 2 weeks
Secondary	Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday)		Baseline and 2 weeks
Secondary	Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight)		Baseline and 2 weeks
Secondary	Mean Non-transformed Amlodipine Plasma Concentration		24 hours post-dose on Day 14
Secondary	Mean Non-transformed Celecoxib Plasma Concentration		24 hours post-dose on Day 14
Secondary	Mean Log-transformed Amlodipine Plasma Concentration		24 hours post-dose on Day 14
Secondary	Mean Log-transformed Celecoxib Plasma Concentration		24 hours post-dose on Day 14
Secondary	Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint		Baseline and 2 weeks