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

NCT02172040 | Completed Phase 3 Results

• 2 other identifiers: KIT-302-03-012013-005381-19
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 10

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

Keywords

High blood pressure; Systolic blood pressure; Diastolic blood pressure; Antihypertensive

Outcome Measures

Primary Outcomes (2)

• Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint

  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 \[i.e., any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug\].

  1 month

Secondary Outcomes (10)

• Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h)

  Baseline and 2 weeks

• Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight)

  Baseline and 2 weeks

• Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h)

  Baseline and 2 weeks

• Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday)

  Baseline and 2 weeks

• Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight)

  Baseline and 2 weeks

Study Arms (4)

Amlodipine+Celecoxib

EXPERIMENTAL

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; Drug: Over-encapsulated 200 mg celecoxib capsule

Amlodipine+Placebo

ACTIVE COMPARATOR

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; Drug: Matched placebo capsule for over-encapsulated celecoxib capsule

Placebo+Celecoxib

PLACEBO COMPARATOR

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; Drug: Matched placebo capsule for over-encapsulated amlodipine besylate tablet

Placebo+Placebo

SHAM COMPARATOR

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; Drug: Matched placebo capsule for over-encapsulated amlodipine besylate tablet

Interventions

Over-encapsulated 10 mg amlodipine besylate tablet DRUG

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

Also known as: Norvasc

Amlodipine+Celecoxib; Amlodipine+Placebo

Matched placebo capsule for over-encapsulated celecoxib capsule DRUG

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

Also known as: Placebo

Amlodipine+Placebo; Placebo+Placebo

Over-encapsulated 200 mg celecoxib capsule DRUG

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

Also known as: Celebrex

Amlodipine+Celecoxib; Placebo+Celecoxib

Matched placebo capsule for over-encapsulated amlodipine besylate tablet DRUG

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

Also known as: Placebo

Placebo+Celecoxib; Placebo+Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult 40 to 75 years of age
• Newly diagnosed hypertension that requires chronic pharmacological therapy. Specifically, the subject must meet both of the following criteria:
• 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
• SBPday \>135 mmHg at Baseline Visit (Day 0)
• Body Mass Index of 18.5 to 34.9 kg/m2
• 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
• A negative pregnancy test at Screening
• Both males and women of child bearing potential agree to use adequate contraceptive methods while on study (from Screening through final study visit)
• Able to comprehend and sign an informed consent form

You may not qualify if:

• 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
• SBPday ≤135 mmHg at baseline (Day 0)
• Weight \<55 kg
• Fragile health
• 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
• Current or recent history (within 4 weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection
• Current clinically significant viral infection
• History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin
• Major surgery within 4 weeks prior to Screening
• Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's disease or chronic pancreatitis)
• Active peptic ulceration or history of gastrointestinal bleeding
• History of myocardial infarction, congestive heart failure, or stroke
• Any current cardiovascular disease
• History of psychotic disorder
• 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

Sponsors & Collaborators

• Kitov Pharmaceuticals, Ltd.: lead

Study Sites (10)

Celerion

Belfast, Antrim, BT9 6AD, United Kingdom

Location

The Medicines Evaluation Unit Ltd.

Manchester, Greater Manchester, M23 9QZ, United Kingdom

Location

Reading Clinical Research Aspect

Ledbury, Herefordshire, HR8 2AA, United Kingdom

Location

Synexus Merseyside Clinical Research Centre

Liverpool, Merseyside, L22 0LG, United Kingdom

Location

Oldfield Surgery

Bath, North East Somerset, BA2 3HT, United Kingdom

Location

Rowden Surgery

Chippenham, Wiltshire, SN15 2SB, United Kingdom

Location

Synexus Midlands Clinical Research Centre

Birmingham, B15 2SQ, United Kingdom

Location

Synexus Scotland Clinical Research Centre

Glasgow, G20 0SP, United Kingdom

Location

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

London, EC1M 6BQ, United Kingdom

Location

Reading Clinical Research Aspect

Reading, RG6 6BZ, United Kingdom

Location

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Celecoxib

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles

Limitations and Caveats

No limitations

Results Point of Contact

• Title: J. Paul Waymack, M.D., Chief Medical Officer
• Organization: Kitov Pharmaceuticals, Ltd.

paul@kitovpharma.com

(202) 965-2215

Study Officials

• J. Paul Waymack, MD, ScD

  Kitov Pharma Ltd

  STUDY DIRECTOR

• 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.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 24, 2014
• Study Start: June 26, 2014
• Primary Completion: November 19, 2015
• Study Completion: November 19, 2015
• Last Updated: October 10, 2018
• Results First Posted: October 3, 2017

Record last verified: 2018-09

Locations

GB (10)