Hypertension
Conditions
Keywords
High blood pressure, Systolic blood pressure, Diastolic blood pressure, Antihypertensive
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.
Interventions
DRUGOver-encapsulated 10 mg amlodipine besylate tablet
Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks
DRUGMatched placebo capsule for over-encapsulated celecoxib capsule
Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks
DRUGOver-encapsulated 200 mg celecoxib capsule
Over-encapsulated 200 mg celecoxib capsule once a day for two weeks
DRUGMatched placebo capsule for over-encapsulated amlodipine besylate tablet
Matched placebo capsule for over-encapsulated amlodipine besylate tablet once a day for two weeks
Sponsors
Kitov Pharmaceuticals, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Adult 40 to 75 years of age 2. Newly diagnosed hypertension that requires chronic pharmacological therapy. Specifically, the subject must meet both of the following criteria: 1. Resting systolic BP ≥140 mmHg and ≤179 mmHg (where resting is defined as supine for at least 10 minutes with minimal interaction) at Initial Screening Visit 2. SBPday \>135 mmHg at Baseline Visit (Day 0) 3. Body Mass Index of 18.5 to 34.9 kg/m2 4. Healthy (other than hypertension) as determined by the Investigator based on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests 5. A negative pregnancy test at Screening 6. Both males and women of child bearing potential agree to use adequate contraceptive methods while on study (from Screening through final study visit) 7. Able to comprehend and sign an informed consent form
Exclusion criteria
1. Resting systolic BP \>179 mmHg or a resting diastolic BP \>110 mmHg at Screening (where resting is defined as supine for at least 10 minutes with minimal interaction) or SBP24h \>169 mmHg or DBP24h \>110 mmHg at randomization 2. SBPday ≤135 mmHg at baseline (Day 0) 3. Weight \<55 kg 4. Fragile health 5. Evidence of clinically significant findings on screening evaluations (clinical, laboratory, and ECG) which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of safety data 6. Current or recent history (within 4 weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection 7. Current clinically significant viral infection 8. History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin 9. Major surgery within 4 weeks prior to Screening 10. Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's disease or chronic pancreatitis) 11. Active peptic ulceration or history of gastrointestinal bleeding 12. History of myocardial infarction, congestive heart failure, or stroke 13. Any current cardiovascular disease 14. History of psychotic disorder 15. History of alcoholism or drug addiction or current alcohol or drug use that, in the opinion of the Investigator, will interfere with the subject's ability to comply with the dosing schedule and study evaluations 16. History of any illicit drug use within one year prior to Screening 17. Positive drug screen at Screening. A positive drug screen for opiates only (with all other drug tests negative) will not be a basis for exclusion if the subject took over-the-counter narcotics as indicated on the product label within 24 hours prior to the drug screen 18. Current treatment or treatment within 30 days prior to first dose of study drugs with another investigational drug or current enrollment in another clinical trial 19. Current treatment or treatment within 30 days prior to first dose of study drugs with an NSAID or systemic corticosteroid 20. Known history of human immunodeficiency virus, hepatitis B, or hepatitis C 21. Known hypersensitivity to amlodipine or celecoxib 22. Known hypersensitivity to the inactive ingredients in the over-encapsulated study drugs 23. Asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic type reactions after taking acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors 24. Subjects who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule and study evaluations 25. Pregnant or lactating 26. Unable to correctly use ambulatory blood pressure monitor after instruction on its use 27. Subjects with Child-Pugh Class B or C cirrhosis; 28. Subjects currently taking a calcium channel blocker for any reason including angina. Subjects will not be withdrawn from these drugs to be enrolled in the trial 29. Creatinine clearance \<50 ml/min as estimated by the Cockroft-Gault equation 30. Known cytochrome P450 2C9 poor metabolizer 31. Subjects with allergy or hypersensitivity to sulfonamides
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) | Baseline and 2 weeks |
| 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 |
| Mean Non-transformed Celecoxib Plasma Concentration | 24 hours post-dose on Day 14 |
| Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) | Baseline and 2 weeks |
Countries
United Kingdom
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine+Celecoxib 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 | 49 |
| Amlodipine+Placebo 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 | 45 |
| Placebo+Celecoxib 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 | 31 |
| Placebo+Placebo 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 | 27 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 0 |
| Overall Study | Family emergency abroad | 0 | 0 | 0 | 1 |
| Overall Study | Not available for Day 13 & 14 visits | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Amlodipine+Celecoxib | Amlodipine+Placebo | Placebo+Celecoxib | Placebo+Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 8 | 57.3 years STANDARD_DEVIATION 9.4 | 54.9 years STANDARD_DEVIATION 8.2 | 52.5 years STANDARD_DEVIATION 9.1 | 56.1 years STANDARD_DEVIATION 8.8 |
| Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) | 148.7 mmHg STANDARD_DEVIATION 7.4 | 147.6 mmHg STANDARD_DEVIATION 8.7 | 150.8 mmHg STANDARD_DEVIATION 8.9 | 147.3 mmHg STANDARD_DEVIATION 8.6 | 148.5 mmHg STANDARD_DEVIATION 8.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 43 Participants | 29 Participants | 26 Participants | 144 Participants |
| Region of Enrollment United Kingdom | 49 Participants | 45 Participants | 31 Participants | 27 Participants | 152 Participants |
| Sex: Female, Male Female | 17 Participants | 19 Participants | 10 Participants | 10 Participants | 56 Participants |
| Sex: Female, Male Male | 32 Participants | 26 Participants | 21 Participants | 17 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 45 | 0 / 31 | 0 / 27 |
| other Total, other adverse events | 17 / 49 | 17 / 45 | 5 / 31 | 6 / 27 |
| serious Total, serious adverse events | 0 / 49 | 0 / 45 | 0 / 31 | 0 / 27 |
Outcome results
Primary
Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk)
Including any untoward medical occurrence in a participant administered study drug, which do not necessarily have a causal relationship with the study drug \[i.e., any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug\].
Time frame: 1 month
Population: Safety population: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amlodipine+Celecoxib | Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk) | 27 Participants |
| Amlodipine+Placebo | Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk) | 28 Participants |
| Placebo+Celecoxib | Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk) | 14 Participants |
| Placebo+Placebo | Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk) | 10 Participants |
p-value: =0.166Chi-squared
Primary
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint
Time frame: Baseline and 2 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint | -10.6 mmHg | Standard Deviation 9.2 |
| Amlodipine+Placebo | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint | -8.83 mmHg | Standard Deviation 8.13 |
| Placebo+Celecoxib | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint | -0.5 mmHg | Standard Deviation 8.8 |
| Placebo+Placebo | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint | -2.11 mmHg | Standard Deviation 8.2 |
Comparison: 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.p-value: =0.001t-test, 1 sided
Comparison: 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.p-value: =0.491t-test, 1 sided
Secondary
Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h)
Time frame: Baseline and 2 weeks
Population: ITT Population as described for primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h) | -7.1 mmHg | Standard Deviation 5.6 |
| Amlodipine+Placebo | Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h) | -4.8 mmHg | Standard Deviation 4.83 |
| Placebo+Celecoxib | Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h) | -0.5 mmHg | Standard Deviation 4.6 |
| Placebo+Placebo | Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h) | 0.22 mmHg | Standard Deviation 4.28 |
p-value: =0.038t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.562t-test, 1 sided
Secondary
Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h)
Time frame: Baseline and 2 weeks
Population: ITT population as described for primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) | -10.3 mmHg | Standard Deviation 8.9 |
| Amlodipine+Placebo | Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) | -8.02 mmHg | Standard Deviation 7.6 |
| Placebo+Celecoxib | Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) | -0.5 mmHg | Standard Deviation 7.8 |
| Placebo+Placebo | Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h) | -1.19 mmHg | Standard Deviation 5.87 |
p-value: 0.177t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.719t-test, 1 sided
Secondary
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday)
Time frame: Baseline and 2 weeks
Population: ITT Population as described for primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday) | -7.5 mmHg | Standard Deviation 6.4 |
| Amlodipine+Placebo | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday) | -5.53 mmHg | Standard Deviation 5.06 |
| Placebo+Celecoxib | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday) | -1.5 mmHg | Standard Deviation 5.6 |
| Placebo+Placebo | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday) | -0.32 mmHg | Standard Deviation 5.39 |
p-value: =0.104t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.002t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.419t-test, 1 sided
Secondary
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint
Time frame: Baseline and 2 weeks
Population: ITT Population as described for primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint | -10.6 mmHg | Standard Deviation 9.2 |
| Amlodipine+Placebo | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint | -8.83 mmHg | Standard Deviation 8.13 |
| Placebo+Celecoxib | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint | -0.5 mmHg | Standard Deviation 8.8 |
| Placebo+Placebo | Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint | -2.11 mmHg | Standard Deviation 8.2 |
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.001t-test, 1 sided
Secondary
Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight)
Time frame: Baseline and 2 weeks
Population: ITT Population as defined for primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight) | -7.0 mmHg | Standard Deviation 8.6 |
| Amlodipine+Placebo | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight) | -3.23 mmHg | Standard Deviation 7.79 |
| Placebo+Celecoxib | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight) | 0.3 mmHg | Standard Deviation 7.1 |
| Placebo+Placebo | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight) | 0.01 mmHg | Standard Deviation 6.23 |
p-value: =0.028t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.051t-test, 1 sided
p-value: =0.074t-test, 1 sided
p-value: =0.878t-test, 1 sided
Secondary
Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight)
Time frame: Baseline and 2 weeks
Population: ITT Population as described for primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) | -10.5 mmHg | Standard Deviation 10.6 |
| Amlodipine+Placebo | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) | -6.35 mmHg | Standard Deviation 11.35 |
| Placebo+Celecoxib | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) | -1.7 mmHg | Standard Deviation 12.3 |
| Placebo+Placebo | Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight) | -1.42 mmHg | Standard Deviation 9.15 |
p-value: =0.069t-test, 1 sided
p-value: =0.001t-test, 1 sided
p-value: <0.001t-test, 1 sided
p-value: =0.097t-test, 1 sided
p-value: =0.064t-test, 1 sided
p-value: =0.924t-test, 1 sided
Secondary
Mean Log-transformed Amlodipine Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Log-transformed Amlodipine Plasma Concentration | 9.634 log(pg/mL) | Standard Deviation 0.268 |
| Amlodipine+Placebo | Mean Log-transformed Amlodipine Plasma Concentration | 10.025 log(pg/mL) | Standard Deviation 0.31 |
p-value: <0.001t-test, 1 sided
Secondary
Mean Log-transformed Celecoxib Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Log-transformed Celecoxib Plasma Concentration | 4.785 log(ng/mL) | Standard Deviation 0.564 |
| Amlodipine+Placebo | Mean Log-transformed Celecoxib Plasma Concentration | 4.636 log(ng/mL) | Standard Deviation 0.781 |
p-value: =0.527t-test, 1 sided
Secondary
Mean Non-transformed Amlodipine Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Amlodipine+Celecoxib | Mean Non-transformed Amlodipine Plasma Concentration | 15,800.83 pg/mL |
| Amlodipine+Placebo | Mean Non-transformed Amlodipine Plasma Concentration | 23,453 pg/mL |
p-value: <0.001t-test, 1 sided
Secondary
Mean Non-transformed Celecoxib Plasma Concentration
Time frame: 24 hours post-dose on Day 14
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Celecoxib | Mean Non-transformed Celecoxib Plasma Concentration | 139.708 ng/mL | Standard Deviation 86.504 |
| Amlodipine+Placebo | Mean Non-transformed Celecoxib Plasma Concentration | 138.667 ng/mL | Standard Deviation 118.811 |
p-value: =0.977t-test, 1 sided