A study to test the effectiveness of a tablet containing both Nifedipine and Candesartan Cilexetil in adults with high blood pressure whose blood pressure is not well controlled with tablets containing 16 mg Candesartan Cilexetil

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2012-004493-26-PL
• Date of registration: 14/06/2013
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: A study to test the effectiveness of a tablet containing both Nifedipine and Candesartan Cilexetil in adults with high blood pressure whose blood pressure is not well controlled with tablets containing 16 mg Candesartan Cilexetil
• Scientific title: A Multicenter, Randomized, Double-Blind, Monotherapy-Controlled Study of Nifedipine Gastrointestinal Therapeutic System and Candesartan Cilexetil in Combination Taken Orally for 8 Weeks in Adult Subjects with Essential Hypertension Who Are Inadequately Controlled on 16 mg Candesartan Cilexetil Monotherapy
• Date of first enrolment: 05/08/2013
• Target sample size: 504
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004493-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Canada, Czech Republic, France, Germany, Lithuania, Poland, Russian Federation, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects 18 years or older are eligible.

2. At Visit 0, subjects not treated with antihypertensive medications are to have MSSBP of = 160 mmHg and < 200 mmHg, and 24 hours MASBP (mean ambulatory systolic blood pressure) = 130 mmHg; those subjects treated with antihypertensive medication are to have MSSBP = 150 mmHg and <200 mmHg, as measured by a calibrated electronic BP measuring device.

3. At Visit 3, subject must have MSSBP = 140 mmHg before randomization.

4. Women of childbearing potential and men must agree to use adequate contraception other than hormonal contraceptives when sexually active. This applies since signing of the IC form until the last study drug administration.

5. Written informed consent
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 252
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 252

Exclusion criteria:
1. MSSBP = 200 mmHg and/or MSDBP = 120 mmHg

2. MSDBP < 60 mmHg

3. If differences greater than 20 mmHg for SBP and 10 mmHg for DBP are present on 3 consecutive BP readings at visit 0, the subject should be excluded from the study.

4. Any history of hypertensive emergency

5. Evidence of secondary hypertension such as coarctation of the aorta, pheochromocytoma, hyperaldosteronism, etc.

6. Cerebrovascular ischemic event (stroke, transient ischemic attack [TIA]) within the previous 12 months

7. History of intracerebral hemorrhage or subarachnoid hemorrhage

8. History of hypertensive retinopathy – known Keith-Wagener Grade III or IV

9. Any history of heart failure, New York Heart Association (NYHA) classification III or IV

10. Severe coronary heart disease as manifest by a history of myocardial infarction or unstable angina in the last 6 months prior to visit 0.

11. Clinically significant cardiac valvular disease

12. Subjects with an aortic aneurysm that, in the opinion of the investigator, will be unsuitable to be enrolled in the study.

13. Type 1 diabetes mellitus (DM) or poorly controlled Type 2 DM as evidenced by glycosylated hemoglobin (HbA1C) of greater than 9% on visit 0.

14. History of malignancy in the last 5 years, excluding treated basal or nonmelanoma skin cancer, or treated cervical carcinoma in situ

15. Hyperkalemia: potassium above the upper limit of normal in the laboratory range

16. Present severe rhythm or conduction disorder , e.g.:

- Atrial fibrillation
- Second or third degree heart block without a pacemaker.

17. Subjects who have night employment (night shift).

18. Surgical or medical conditions that might alter the metabolism, excretion or distribution or absorption of any drug

- Gastrointestinal disease or surgery resulting in the potential for
malabsorption with the exception of lactose intolerance

- Severe gastro-intestinal tract narrowing; gastric banding; kock pouch (ileostomy after proctocolectomy)

- Cholestasis or biliary obstruction or history of pancreatic injury or disease.

- Liver disease or AST or ALT levels >3 x upper limit of normal (ULN) at Screening Visit

- Renal insufficiency, defined as estimated glomerular filtration rate (estimated GFR) of < 30 mL/min (see Section 7.6.3), or on
hemodialysis

19. For subjects with renal impairment, reduction of estimated GFR = 30% at Visit 2 compared with Screening visit as confirmed by a repeat laboratory test performed within 1 week

20. Investigational study participation with receipt of investigational study medication within the last month

21. Previous assignment to treatment in this study

22. Allergies or known intolerance to one of the investigational drugs/drug class or to one of their ingredients

23. Female subjects who are pregnant or lactating.

24. History of non-compliance, alcoholism, drug abuse or any other condition that in the opinion of the investigator will compromise successful completion of the study.

25. Subjects with pre-planned surgery during the course of the study

26. Inability to stop any of the medications listed in the prohibited concomitant medication list

27. Subjects who are on treatment with any drug approved for the treatment of hypertension, when prescribed for any reason other than control of blood pressure.

28. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Essential Hypertension
MedDRA version: 21.1 Level: PT Classification code 10015488 Term: Essential hypertension System Organ Class: 10047065 - Vascular disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Nifedipine GITS/Candesartan cilexetil 30/16
Product Code: BAY98-7106
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NIFEDIPINE
CAS Number: 21829-25-4
Current Sponsor code: BAYa1040
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
INN or Proposed INN: CANDESARTAN CILEXETIL
CAS Number: 145040-37-5
Current Sponsor code: BAY12-9333
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 16-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Nifedipine GITS/Candesartan cilexetil 60/16
Product Code: BAY98-7106
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NIFEDIPINE
CAS Number: 21829-25-4
Current Sponsor code: BAYa1040
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
INN or Proposed INN: CANDESARTAN CILEXETIL
CAS Number: 145040-37-5
Current Sponsor code: BAY12-9333
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 16-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Atacand 16 mg
Product Name: Candesartan Cilexetil
Pharmaceutical Form: Capsule
INN or Proposed INN: CANDESARTAN CILEXETIL
CAS Number: 145040-37-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 16-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8

Main Objective: The primary objective is to demonstrate the efficacy of two FDCs of nifedipine GITS and candesartan cilexetil compared to candesartan cilexetil monotherapy in subjects not adequately controlled on candesartan cilexetil alone, based on reduction of mean seated systolic blood pressure (MSSBP).

Primary end point(s): The primary efficacy variable will be change from baseline in MSSBP at Week 8.

Secondary Objective: - To demonstrate the efficacy of the FDCs of Nifedipine GITS/ candesartan cilexetil based on reduction of mean seated diastolic blood pressure (MSDBP), response rate and control rate

- To demonstrate the efficacy of the FDCs of Nifedipine GITS/ candesartan cilexetil based on reduction of mean diastolic blood pressure (DBP) and systolic blood pressure (SBP) on ABPM over a 24-h period, during both the daytime and night-time.

- To explore the safety and tolerability of the FDC treatments

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8

Secondary end point(s): As a secondary endpoint, this study will evaluate DBP reductions, as well as predefined response, control criteria and the mean change in SBP and DBP on ABPM over 24-hour period, during both daytime and night time at Week 8

Secondary ID(s)

2012-004493-26-DE

No subjects were recruited, no results available

BAY98-7106/14727

Source(s) of Monetary Support

Bayer HealthCare AG

Ethics review

Status: Approved
Approval date:
Contact: