Hypertension MedDRA version: 18.1 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: Norvasc
Product Name: amlodipine besylate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: AMLODIPINE (AMLODIPINE BESYLATE)
CAS Number: 111470-99-6
Other descriptive name: AMLODIPIN
Sponsors
Kitov Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria A subject may be included in this study if he or she meets all of the following 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: a. 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; b. SBPday > 135 mmHg at Baseline Visit (Day 0); 3. BMI 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 ECG, and clinical laboratory tests; 5. A negative pregnancy test at Screening; 6. Both males and WCBP agree to use adequate contraceptive methods while on study (from Screening through final study visit); Adequate contraceptive methods include those with a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as abstinence from sexual intercourse, and some double barrier methods (condom with spermicide) in conjunction with use by the partner of an IUD, diaphragm with spermicide, oral contraceptives, birth control patch or vaginal ring, oral, or injectable or implanted contraceptives. Abstinence is acceptable only as true abstinence: when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. A woman that is postmenopausal (=2 years since last menstrual period) or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) is not considered a WCBP. 7. Able to comprehend and sign an ICF. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 115 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: A subject will be excluded from this study if he or she meets any of the following 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 an SBP24h > 169 mmHg or DBP24h > 110 mmHg immediately prior to scheduled 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 four 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 four 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 a NSAID or systemic corticosteroid; 20. Known history of HIV, hepatitis B, or hepatitis C; 21. Known hypersensitivity to amlodipine or celecoxib; 22. Known hypersensitivity to the inactive ingredients in the OE 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 (COX-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 correctly to use ABPM after instruction on its use; 27. Subjects with Child-Pugh Class B or C cirrhosis (Appendix I); 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 (CYP2C9) poor metabolizer; 31. Subjects with allergy or hypersensitivity to sulfonamides.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary Endpoint The primary efficacy endpoint for this trial will be the difference, between treatment arms 1 and 2, in the mean change in SBPday from Day 0 to Day 14. Using a hierarchical analysis plan, the secondary and tertiary efficacy endpoints will be comparing treatment arms 3 and 4, followed by treatment arms 1 and 3. ;Main Objective: The primary efficacy objective of this study is to demonstrate that the mean reduction in average daytime (9:00 to 21:00) ambulatory systolic blood pressure (SBPday) after oral administration of amlodipine tablets (10 mg) and celecoxib capsules (200 mg) given together (arm 1) qd for 14 days in adult subjects with newly diagnosed hypertension is no less than half the mean reduction in SBPday after oral administration of amlodipine tablets (10 mg) given alone (i.e., with matched celecoxib placebo; arm 2) qd for 14 days in the same population. Primary Safety Objective The primary safety objective of this study is to evaluate the safety of amlodipine tablets and celecoxib capsules given together qd for 14 days. ;Secondary Objective: The secondary efficacy objectives for this trial are to evaluate the differences, between treatment arm 1 and treatment arm 4, in the change in SBPday and between treatment arm 1 and treatment arms 2, 3 & 4, in the changes in average 24-hour ambulatory systolic blood pressure (SBP24h), average night-time (01:00 to 06:00) ambulatory systolic blood pressure (SBPnight), average 24 hour ambulatory diastolic blood pressure (DBP24h), average daytime (9:00 to 21:00) diastolic systolic blood pressure (DBPday) and average night-time (01:00 to 06:00) diastolic systolic blood pressure (DBPnight) from Day 0 to Day 14. An additional secondary objective of this trial is to evaluate for PK drug-drug interactions by comparing amlodipine and celecoxib plasma levels at Day 14 between treatment arm 1 and treatment arm 2 and between treatment arm 1 and treatment arm 3. The PK population will consist | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints The secondary efficacy endpoints for this trial will be the differences, between treatment arm 1 and treatment arm 4, in the mean change in SBPday and between treatment arm 1 and treatment arms 2, 3 & 4, in the mean changes in SBP24h, SBPnight, DBP24h, DBPday and DBPnight, as measured by ABPM, from Day 0 to Day 14. An additional secondary endpoint for this trial will be the differences, between treatment arms 1 and 2 and between treatment arms 1 and 3, in plasma concentrations of amlodipine and celecoxib at Day 14 to investigate for possible PK drug-drug interactions. The PK population will consist of a subset of the overall trial population; approximately 60 subjects randomized 1.5:1.5:1:1 will have blood drawn for the PK analysis. Safety will also be an endpoint and will be assessed primarily based on reported AEs. The severity of AEs will be graded according to World Health Organization (WHO) Toxicity Criteria. Secondary safety assessments will include physical examination, vital signs, orthostatic hypotension evaluations, ECG, hematology, serum chemistry, and urinalysis. ;Timepoint(s) of evaluation of this end point: Day 0 to Day 14 | — |
Countries
United Kingdom
Contacts
Public ContactMedical Monitor
Kitov Pharmaceuticals Ltd
Outcome results
None listed