Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy
Sponsor
Kitov Pharmaceuticals, Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT02172040
Collaborator
(none)
152
10
4
16.8
15.2
0.9
Study Details
Study Description
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."
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
152 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Jun 26, 2014
Actual Primary Completion Date
:
Nov 19, 2015
Actual Study Completion Date
:
Nov 19, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Amlodipine+Celecoxib 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
Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks
Other Names:
Drug: Over-encapsulated 200 mg celecoxib capsule
Over-encapsulated 200 mg celecoxib capsule once a day for two weeks
Other Names:
|
| Active Comparator: Amlodipine+Placebo 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
Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks
Other Names:
Drug: Matched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
Other Names:
|
| Placebo Comparator: Placebo+Celecoxib 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
Over-encapsulated 200 mg celecoxib capsule once a day for two weeks
Other Names:
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
Other Names:
|
| Sham Comparator: 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 |
Drug: Matched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
Other Names:
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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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) [1 month]
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].
Secondary Outcome Measures
- 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]
- Mean Non-transformed Amlodipine Plasma Concentration [24 hours post-dose on Day 14]
- Mean Non-transformed Celecoxib Plasma Concentration [24 hours post-dose on Day 14]
- Mean Log-transformed Amlodipine Plasma Concentration [24 hours post-dose on Day 14]
- Mean Log-transformed Celecoxib Plasma Concentration [24 hours post-dose on Day 14]
- Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint [Baseline and 2 weeks]
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
-
History of any illicit drug use within one year prior to Screening
-
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
-
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
-
Current treatment or treatment within 30 days prior to first dose of study drugs with an NSAID or systemic corticosteroid
-
Known history of human immunodeficiency virus, hepatitis B, or hepatitis C
-
Known hypersensitivity to amlodipine or celecoxib
-
Known hypersensitivity to the inactive ingredients in the over-encapsulated 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 for any reason including angina. Subjects will not be withdrawn from these drugs to be enrolled in the trial
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Celerion | Belfast | Antrim | United Kingdom | BT9 6AD |
| 2 | The Medicines Evaluation Unit Ltd. | Manchester | Greater Manchester | United Kingdom | M23 9QZ |
| 3 | Reading Clinical Research Aspect | Ledbury | Herefordshire | United Kingdom | HR8 2AA |
| 4 | Synexus Merseyside Clinical Research Centre | Liverpool | Merseyside | United Kingdom | L22 0LG |
| 5 | Oldfield Surgery | Bath | North East Somerset | United Kingdom | BA2 3HT |
| 6 | Rowden Surgery | Chippenham | Wiltshire | United Kingdom | SN15 2SB |
| 7 | Synexus Midlands Clinical Research Centre | Birmingham | United Kingdom | B15 2SQ | |
| 8 | Synexus Scotland Clinical Research Centre | Glasgow | United Kingdom | G20 0SP | |
| 9 | 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 | EC1M 6BQ | |
| 10 | Reading Clinical Research Aspect | Reading | United Kingdom | RG6 6BZ |
Sponsors and Collaborators
- Kitov Pharmaceuticals, Ltd.
Investigators
- Study Director: J. Paul Waymack, MD, ScD, Kitov Pharma Ltd
- Principal Investigator: 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.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Kitov Pharmaceuticals, Ltd.
ClinicalTrials.gov Identifier:
NCT02172040
Other Study ID Numbers:
- KIT-302-03-01
- 2013-005381-19
First Posted:
Jun 24, 2014
Last Update Posted:
Oct 10, 2018
Last Verified:
Sep 1, 2018
Keywords provided by Kitov Pharmaceuticals, Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants underwent assessments to determine eligibility at the Initial Screening Visit (Day -7 to -2; 458 participants), Final Screening Visit (Day -1; 228 participants), and the morning prior to randomization (Study Day 0; 227 participants). A total of 306 participants were screen failures and the remaining 152 were randomized. |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Period Title: Overall Study | ||||
| STARTED | 49 | 45 | 31 | 27 |
| COMPLETED | 49 | 42 | 29 | 26 |
| NOT COMPLETED | 0 | 3 | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Total of all reporting groups |
| Overall Participants | 49 | 45 | 31 | 27 | 152 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
57.7
(8.0)
|
57.3
(9.4)
|
54.9
(8.2)
|
52.5
(9.1)
|
56.1
(8.8)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
17
34.7%
|
19
42.2%
|
10
32.3%
|
10
37%
|
56
36.8%
|
| Male |
32
65.3%
|
26
57.8%
|
21
67.7%
|
17
63%
|
96
63.2%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
6.1%
|
0
0%
|
1
3.2%
|
1
3.7%
|
5
3.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
4.4%
|
1
3.2%
|
0
0%
|
3
2%
|
| White |
46
93.9%
|
43
95.6%
|
29
93.5%
|
26
96.3%
|
144
94.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||||
| United Kingdom |
49
100%
|
45
100%
|
31
100%
|
27
100%
|
152
100%
|
| Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) (mmHg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mmHg] |
148.7
(7.4)
|
147.6
(8.7)
|
150.8
(8.9)
|
147.3
(8.6)
|
148.5
(8.4)
|
Outcome Measures
| Title | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT): All randomized participants who received at least 1 dose of study drug and had at least a valid baseline ambulatory blood pressure monitor measurement (ABPM) and either: a) a valid Day 13-14 ABPM, where participant completed treatment or b) a valid Day 6-7 or Day 0-1 ABPM, where participant was withdrawn early. |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-10.6
(9.2)
|
-8.83
(8.13)
|
-0.5
(8.8)
|
-2.11
(8.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | A serial gatekeeping strategy was used for the primary efficacy endpoint analysis. The primary comparison was a two-sample t-test to test the one-sided hypothesis that treatment with amlodipine + celecoxib was non-inferior to half of the effect achieved with amlodipine. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority margin definition: lower limit of the 95% confidence interval (CI) for amlodipine + celecoxib arm did not cross the 50% value for the amlodipine arm. | |
| Statistical Test of Hypothesis | p-Value | = 0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | A serial gatekeeping strategy was used for the primary efficacy endpoint analysis. The secondary comparison was a two-sample t-test to test the one-sided hypothesis that treatment with placebo was superior to treatment with celecoxib. This was only to be performed if statistical significance was achieved for the primary comparison. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.491 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk) |
|---|---|
| Description | 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]. |
| Time Frame | 1 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population: all randomized participants who received at least one dose of study drug. |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 31 | 27 |
| Count of Participants [Participants] |
27
55.1%
|
28
62.2%
|
14
45.2%
|
10
37%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo, Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.166 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Title | Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population as described for primary outcome |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-10.3
(8.9)
|
-8.02
(7.6)
|
-0.5
(7.8)
|
-1.19
(5.87)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.177 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.719 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population as described for primary outcome |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-10.5
(10.6)
|
-6.35
(11.35)
|
-1.7
(12.3)
|
-1.42
(9.15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.069 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.097 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.064 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.924 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h) |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population as described for primary outcome |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-7.1
(5.6)
|
-4.8
(4.83)
|
-0.5
(4.6)
|
0.22
(4.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.038 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.562 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday) |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population as described for primary outcome |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-7.5
(6.4)
|
-5.53
(5.06)
|
-1.5
(5.6)
|
-0.32
(5.39)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.104 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.002 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.419 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight) |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population as defined for primary outcome |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-7.0
(8.6)
|
-3.23
(7.79)
|
0.3
(7.1)
|
0.01
(6.23)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.028 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.051 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.074 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.878 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Non-transformed Amlodipine Plasma Concentration |
|---|---|
| Description | |
| Time Frame | 24 hours post-dose on Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No amlodipine PK statistical analyses were performed for the PK participants in the placebo+celecoxib and placebo+placebo arms. |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo |
|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 |
| Measure Participants | 24 | 20 |
| Mean (Standard Deviation) [pg/mL] |
15,800.83
(4,161.929)
|
23,453
(5,746.337)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Non-transformed Celecoxib Plasma Concentration |
|---|---|
| Description | |
| Time Frame | 24 hours post-dose on Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No celecoxib PK statistical analyses were performed for the PK participants in the amlodipine+placebo and placebo+placebo arms. |
| Arm/Group Title | Amlodipine+Celecoxib | Placebo+Celecoxib |
|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet 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 tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 24 | 15 |
| Mean (Standard Deviation) [ng/mL] |
139.708
(86.504)
|
138.667
(118.811)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.977 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Log-transformed Amlodipine Plasma Concentration |
|---|---|
| Description | |
| Time Frame | 24 hours post-dose on Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No amlodipine PK statistical analyses were performed for the PK participants in the placebo+celecoxib and placebo+placebo arms. |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo |
|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 |
| Measure Participants | 24 | 20 |
| Mean (Standard Deviation) [log(pg/mL)] |
9.634
(0.268)
|
10.025
(0.310)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Log-transformed Celecoxib Plasma Concentration |
|---|---|
| Description | |
| Time Frame | 24 hours post-dose on Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No celecoxib PK statistical analyses were performed for the PK participants in the amlodipine+placebo and placebo+placebo arms. |
| Arm/Group Title | Amlodipine+Celecoxib | Placebo+Celecoxib |
|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet 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 tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 24 | 15 |
| Mean (Standard Deviation) [log(ng/mL)] |
4.785
(0.564)
|
4.636
(0.781)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Amlodipine+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.527 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint |
|---|---|
| Description | |
| Time Frame | Baseline and 2 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population as described for primary outcome |
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo |
|---|---|---|---|---|
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks |
| Measure Participants | 49 | 45 | 30 | 26 |
| Mean (Standard Deviation) [mmHg] |
-10.6
(9.2)
|
-8.83
(8.13)
|
-0.5
(8.8)
|
-2.11
(8.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Celecoxib, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Celecoxib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Amlodipine+Placebo, Placebo+Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Adverse Events
| Time Frame | 1 month | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo | ||||
| Arm/Group Description | Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks | Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks 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 | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg 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 tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule 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 Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks | ||||
All Cause Mortality |
||||||||
| Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/49 (0%) | 0/45 (0%) | 0/31 (0%) | 0/27 (0%) | ||||
Serious Adverse Events |
||||||||
| Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/49 (0%) | 0/45 (0%) | 0/31 (0%) | 0/27 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/49 (34.7%) | 17/45 (37.8%) | 5/31 (16.1%) | 6/27 (22.2%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 2/49 (4.1%) | 2 | 4/45 (8.9%) | 4 | 0/31 (0%) | 0 | 0/27 (0%) | 0 |
| General disorders | ||||||||
| Oedema peripheral | 4/49 (8.2%) | 4 | 7/45 (15.6%) | 8 | 0/31 (0%) | 0 | 0/27 (0%) | 0 |
| Infections and infestations | ||||||||
| Nasopharyngitis | 5/49 (10.2%) | 5 | 0/45 (0%) | 0 | 2/31 (6.5%) | 2 | 0/27 (0%) | 0 |
| Upper respiratory tract infection | 0/49 (0%) | 0 | 2/45 (4.4%) | 3 | 2/31 (6.5%) | 2 | 1/27 (3.7%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Gout | 0/49 (0%) | 0 | 0/45 (0%) | 0 | 0/31 (0%) | 0 | 2/27 (7.4%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Joint swelling | 5/49 (10.2%) | 5 | 3/45 (6.7%) | 4 | 0/31 (0%) | 0 | 0/27 (0%) | 0 |
| Nervous system disorders | ||||||||
| Headache | 4/49 (8.2%) | 5 | 6/45 (13.3%) | 10 | 2/31 (6.5%) | 3 | 2/27 (7.4%) | 2 |
| Vascular disorders | ||||||||
| Orthostatic hypotension | 0/49 (0%) | 0 | 2/45 (4.4%) | 3 | 0/31 (0%) | 0 | 2/27 (7.4%) | 2 |
Limitations/Caveats
No limitations
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | J. Paul Waymack, M.D., Chief Medical Officer |
|---|---|
| Organization | Kitov Pharmaceuticals, Ltd. |
| Phone | (202) 965-2215 |
| paul@kitovpharma.com |
Responsible Party:
Kitov Pharmaceuticals, Ltd.
ClinicalTrials.gov Identifier:
NCT02172040
Other Study ID Numbers:
- KIT-302-03-01
- 2013-005381-19
First Posted:
Jun 24, 2014
Last Update Posted:
Oct 10, 2018
Last Verified:
Sep 1, 2018