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HypertensionPhase 3NCT02979197

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

A Phase 3 study testing OE 10 mg amlodipine besylate tablet and OE 200 mg celecoxib capsule in people with Hypertension, run by Kitov Pharma Ltd at 9 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 75 years
Conditions the study is for
Hypertension
What is being tested?
OE 10 mg amlodipine besylate tablet and OE 200 mg celecoxib capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
105 participants
Where
9 sitesUnited Kingdom
Study dates
3 Nov 2016to 21 Jul 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 30Show fewer
  • 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
  • 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
  • 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
  • Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Known hypersensitivity to amlodipine or celecoxib
  • Known hypersensitivity to the inactive ingredients in the over-encapsulated (OE) study drugs
  • Asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic type reactions after taking acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors
  • Subjects who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule and study evaluations
  • Pregnant or lactating
  • Unable to correctly use ambulatory blood pressure monitor after instruction on its use
  • Subjects with Child-Pugh Class B or C cirrhosis
  • 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
  • Subjects that took a calcium channel blocker in the past for any indication
  • Creatinine clearance < 50 ml/min as estimated by the Cockroft-Gault equation
  • Known cytochrome P450 2C9 poor metabolizer
  • Subjects with allergy or hypersensitivity to sulfonamides

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United Kingdom9 sites
  • Oldfield Surgery

    Bath, BA2 3HT

  • Celerion

    Belfast, BT9 6AD

  • Hathaway Medical Centre

    Chippenham, SN14 8GT

  • Rowden Surgery

    Chippenham, SN15 2SB

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

    London, EC1M 6BQ

  • Medicines Evaluation Unit Ltd.

    Manchester, M23 9QZ

  • St Chad's Surgery

    Radstock, BA3 2UH

  • Bradford Road Medical Centre

    Trowbridge, BA1 49AR

  • Adcroft Surgery

    Trowbridge, BA14 8QA

Other trials in United Kingdom

About this study

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

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.

Read more

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."

Read the detailed description

This was a multi-center, randomized, double blind, placebo controlled study to evaluate the effect of celecoxib on the efficacy, safety, and pharmacokinetics of amlodipine in subjects with existing hypertension requiring antihypertensive therapy. Approximately 105 eligible subjects were to be randomized 3:3:1 to one of three treatment arms.

Arm 1:OE 10 mg Norvasc tablet+OE 200 mg Celebrex capsule (amlodipine+celecoxib arm)

Arm 2:OE 10 mg Norvasc tablet+matched placebo for OE Celebrex capsule (amlodipine+placebo arm)

Arm 3:Matched placebo for OE Norvasc tablet+matched placebo for OE Celebrex capsule (placebo+placebo arm).

Following an up to 14-day screening phase, eligible subjects were randomized to one of the 3 treatment arms. All drugs were to be administered orally qd for 14 days for a total of 14 doses. Visits at the clinic took place at the start and at the end of the screening phase, at Study Day 0 (start of treatment), Day 6, Day 7, Day 13 (end of treatment), Day 14 and Day 28 (end of follow-up).

Conditions
Hypertension
Being tested
OE 10 mg amlodipine besylate tablet, OE 200 mg celecoxib capsule, Matched placebo for OE amlodipine besylate tablet, Matched placebo for OE celecoxib capsule
Keywords
High blood pressure, Systolic blood pressure, Diastolic blood pressure, Antihypertensive
Medical subject headings
Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OE 10 mg amlodipine besylate tabletDrug

    Also called OE 10 mg Norvasc tablet

  • OE 200 mg celecoxib capsuleDrug

    Also called OE 200 mg Celebrex capsule

  • Matched placebo for OE amlodipine besylate tabletDrug

    Also called Matched placebo for OE Norvasc tablet

  • Matched placebo for OE celecoxib capsuleDrug

    Also called Matched placebo for OE Celebrex capsule

Study groups in NCT02979197
Study groupRoleWhat they receive
Amlodipine+CelecoxibExperimentalOE 10 mg amlodipine besylate tablet + OE 200 mg celecoxib capsule qd for 14 days
Receives: Drug: OE 10 mg amlodipine besylate tablet; Drug: OE 200 mg celecoxib capsule
Amlodipine+PlaceboActive comparatorOE 10 mg amlodipine besylate tablet + matched placebo for OE celecoxib capsule qd for 14 days
Receives: Drug: OE 10 mg amlodipine besylate tablet; Drug: Matched placebo for OE celecoxib capsule
Placebo+PlaceboSham comparatorMatched placebo for OE amlodipine besylate tablet + matched placebo for OE celecoxib capsule qd for 14 days
Receives: Drug: Matched placebo for OE amlodipine besylate tablet; Drug: Matched placebo for OE celecoxib capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and 14 days

Secondary outcomes (7)
  1. Change in Body Weight

    Body weight was measured at the Initial Screening Visit (Day -10 to -14), at Baseline (Day 0), and at Days 7 and 14. The measurements were made using a calibrated scale with the subject wearing underwear and a light gown. Change in body weight was calculated by subtracting the Baseline value from the end of treatment value (recorded on Day 14). If the Day 14 value was not available, the Day 7 value was used (LOCF method). A negative value for change in body weight indicates a decrease in body weight and a positive value indicates an increase.

    Measured: Baseline and 14 days

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

    An 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. SBP24h was calculated by averaging all of the systolic blood pressure measurements between the protocol-defined first \& last study measurements of the period; measurements during the first hour (white-coat window) were not included. Change in SBP24h 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 (LOCF method). A negative value for change in SBP24h indicates a decrease in systolic blood pressure and a positive value indicates an increase.

    Measured: Baseline and 14 days

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

    An 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. DBP24h was calculated by averaging all of the diastolic blood pressure measurements between the protocol-defined first \& last study measurements of the period; measurements during the first hour (white-coat window) were not included. Change in DBP24h 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 (LOCF method). A negative value for change in DBP24h indicates a decrease in diastolic blood pressure and a positive value indicates an increase.

    Measured: Baseline and 14 days

  4. Change in Creatinine Clearance

    Subjects had blood collected for the measurement of creatinine at the Initial Screening Visit (Day -10 to -14), at Baseline (Day 0), and at Days 7 and 14. Estimated creatinine clearance was calculated using Cockcroft-Gault equation: (140 - age) X body weight (kg)/72 X serum creatinine concentration (mg/dL); multiplied by 0.85 for women. Change in creatinine clearance was calculated by subtracting the Baseline value from the end of treatment value (recorded on Day 14). If the Day 14 value was not available, the Day 7 value was used (LOCF method). A negative value for change in creatinine clearance indicates a decrease in creatinine clearance and a positive value indicates an increase.

    Measured: Baseline and 14 days

  5. Occurrence of Treatment Emergent Adverse Events

    Treatment emergent adverse events (TEAEs) included any untoward medical occurrence that initiated or worsened after the first dose of study drugs and within 14 days of the last dose of study drugs.

    Measured: 1 month

  6. Non-transformed Plasma Concentration of Amlodipine

    A venous blood sample was collected 24 hours ± 1 hour after the last dose of study drugs (i.e., on Day 14). The blood sample was processed to plasma and the concentration of amlodipine measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The resulting concentrations, without logarithmic transformation, were used for the comparison between the amlodipine+celecoxib and amlodipine+placebo arms to evaluate the effect of celecoxib on the mean non-transformed plasma concentrations of amlodipine.

    Measured: 24 hours post-dose on Day 14

  7. Log-transformed Plasma Concentration of Amlodipine

    A venous blood sample was collected 24 hours ± 1 hour after the last dose of study drugs (i.e., on Day 14). The blood sample was processed to plasma and the concentration of amlodipine measured using a validated LC-MS/MS method. The concentrations were logarithmically transformed and used for the comparison between the amlodipine+celecoxib and amlodipine+placebo arms to evaluate the effect of celecoxib on the mean log-transformed plasma concentrations of amlodipine.

    Measured: 24 hours post-dose on Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2016 (estimated)
  2. Study start3 Nov 2016
  3. Primary completion21 Jul 2017
  4. Study completion21 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02979197
Sponsor's protocol ID
KIT-302-03-02
Other IDs
2016-002214-47, 2016
Status last verified
Sep 2019
First submitted
29 Nov 2016
Last updated
21 Oct 2019
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing OE 10 mg amlodipine besylate tablet and OE 200 mg celecoxib capsule in people with Hypertension, run by Kitov Pharma Ltd at 9 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) (time frame: Baseline and 14 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2019.

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