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

NCT02979197 | Completed Phase 3 Results

• 2 other identifiers: KIT-302-03-022016-002214-47
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study was to evaluate the effect of celecoxib on the efficacy and safety of amlodipine besylate on renal and vascular function in subjects with existing hypertension requiring antihypertensive therapy. 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 (KIT-302-03-02), commercial celecoxib capsules (Celebrex®) and commercial amlodipine besylate tablets (Norvasc®) were separately over-encapsulated (OE) and matched placebos were used to allow for blinding. Kitov 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) was conducted to quantify the beneficial renovascular effects noted in the prior study in subjects with existing hypertension requiring antihypertensive therapy. On May 31, 2018, the United States (US) Food and Drug Administration (FDA) 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 (1)

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

  An ambulatory blood pressure monitor (ABPM) fitted to upper arm was used for continuous recording of blood pressure over three 25-hour periods: Days -1 to 0 (Baseline), Days 6 to 7, \& Days 13 to 14. The ABPM recorded blood pressure every 20 minutes between 09:00 and 21:59 and every 30 minutes between 22:00 and 08:59. SBPday was calculated by averaging all of the systolic blood pressure measurements between the protocol-defined first \& last study measurements of the period that fell between 9:00 and 21:00; measurements during the first hour (white-coat window) were not included. Change in SBPday was calculated by subtracting the Baseline value from the end of study value (Day 13 to Day 14 period). If the Day 13 to Day 14 value was not available, the Day 6 to Day 7 value was used \[last observation carried forward (LOCF) method\]. A negative value for change in SBPday indicates a decrease in systolic blood pressure and a positive value indicates an increase.

  Baseline and 14 days

Secondary Outcomes (7)

• Change in Body Weight

  Baseline and 14 days

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

  Baseline and 14 days

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

  Baseline and 14 days

• Change in Creatinine Clearance

  Baseline and 14 days

• Occurrence of Treatment Emergent Adverse Events

  1 month

Other Outcomes (1)

• Change in Serum Creatinine

  Baseline and 14 Days

Study Arms (3)

Amlodipine+Celecoxib

EXPERIMENTAL

OE 10 mg amlodipine besylate tablet + OE 200 mg celecoxib capsule qd for 14 days

Drug: OE 10 mg amlodipine besylate tablet; Drug: OE 200 mg celecoxib capsule

Amlodipine+Placebo

ACTIVE COMPARATOR

OE 10 mg amlodipine besylate tablet + matched placebo for OE celecoxib capsule qd for 14 days

Drug: OE 10 mg amlodipine besylate tablet; Drug: Matched placebo for OE celecoxib capsule

Placebo+Placebo

SHAM COMPARATOR

Matched placebo for OE amlodipine besylate tablet + matched placebo for OE celecoxib capsule qd for 14 days

Drug: Matched placebo for OE amlodipine besylate tablet; Drug: Matched placebo for OE celecoxib capsule

Interventions

OE 10 mg amlodipine besylate tablet DRUG

Also known as: OE 10 mg Norvasc tablet

Amlodipine+Celecoxib; Amlodipine+Placebo

OE 200 mg celecoxib capsule DRUG

Also known as: OE 200 mg Celebrex capsule

Amlodipine+Celecoxib

Matched placebo for OE amlodipine besylate tablet DRUG

Also known as: Matched placebo for OE Norvasc tablet

Placebo+Placebo

Matched placebo for OE celecoxib capsule DRUG

Also known as: Matched placebo for OE Celebrex capsule

Amlodipine+Placebo; 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
• Existing hypertension that is being treated using pharmacological therapy with a single agent that is not a calcium channel blocker
• 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)
• 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 initial screening visit
• If woman of childbearing potential, agree to use a highly effective form of birth control while on study (from Screening through final study visit)
• Able to comprehend and sign an informed consent form.

You may not qualify if:

• 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)
• 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 four weeks prior to initial screening visit) 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 four weeks prior to initial screening visit
• 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 (other than hypertension)
• 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
• History of any illicit drug use within one year prior to initial screening visit

Sponsors & Collaborators

• Kitov Pharma Ltd: lead

Study Sites (9)

Oldfield Surgery

Bath, BA2 3HT, United Kingdom

Location

Celerion

Belfast, BT9 6AD, United Kingdom

Location

Hathaway Medical Centre

Chippenham, SN14 8GT, United Kingdom

Location

Rowden Surgery

Chippenham, SN15 2SB, United Kingdom

Location

Barts Health NHS Trust, Barts Queen Mary University of London, William Harvey Heart Centre

London, EC1M 6BQ, United Kingdom

Location

Medicines Evaluation Unit Ltd.

Manchester, M23 9QZ, United Kingdom

Location

St Chad's Surgery

Radstock, BA3 2UH, United Kingdom

Location

Bradford Road Medical Centre

Trowbridge, BA1 49AR, United Kingdom

Location

Adcroft Surgery

Trowbridge, BA14 8QA, 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

Results Point of Contact

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

paul@kitovpharma.com

(202) 965-2215

Study Officials

• J. Paul Waymack, MD, PhD

  Kitov Pharma Ltd

  STUDY DIRECTOR

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: FACTORIAL
• Sponsor Type: UNKNOWN
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 1, 2016
• Study Start: November 3, 2016
• Primary Completion: July 21, 2017
• Study Completion: July 21, 2017
• Last Updated: October 21, 2019
• Results First Posted: October 21, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (9)