| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with essential hypertension |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | M15 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10015488 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To demonstrate that supportive measures improve drug adherence in patients with mild essential hypertension treated with valsartan 160 mg or valsartan 160 mg plus HCTZ 12.5 mg for 34 weeks. To assess adherence, data on compliance and persistence will be collected.
For primary efficacy the daily proportion of patients taking one tablet of the prescribed hypertensive therapy between 07:00 and 11:00AM will be assessed using an electronic monitor (MEMS) and will be compared between randomized groups over the course of the study.
|
|
| E.2.2 | Secondary objectives of the trial |
Adherence to the prescribed regimen defines the patient’s general tendency to follow medical advice. It is therefore useful to define two substituent terms: (a) compliance, and (b) persistence. The former is defined as ‘the degree of correspondence between the patient’s actual dosing history and the prescribed dosing regimens. The latter is defined as ‘the time elapsed between the first dose taken and time of treatment discontinuation’. Both components will be compared between randomized groups over time.
To assess discrepancies between pill counts, Morisky questionnaire and electronic monitoring to estimate patient adherence to prescribed therapy
To assess the relation between drug exposure and BP reduction.
To assess the relation between drug exposure and the likelihood to switch to valsartan 160 mg plus HCTZ 12.5 mg
To assess the safety and tolerability of valsartan 160 mg and valsartan 160 mg plus HCTZ 12.5 mg.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Male or female patients >= 18 years
2. Patients with mild essential hypertension (MSDBP >= 90 mmHg and < 100 mmHg and/or MSSBP >= 140 mmHg and < 160 mmHg) at visits 1 and 2 not having been treated with antihypertensive drugs before or not having been treated with antihypertensive drugs for at least one year prior to visit 1
3. Written informed consent to participate in the study prior to any study procedures
|
|
| E.4 | Principal exclusion criteria |
1. MSSBP ≥ 160 mmHg and/or MSDBP ≥ 100 mmHg at any time between Visit 1 and 2
2. Patients currently requiring / likely to require any regular long-term drug treatment, i.e. for more than 28 days, (e.g., asthma, COPD, diabetes, rheumatoid arthritis, pain medication, depression, psychotropic drugs, inflammatory bowel disease, estrogen replacement therapy, thyroid hormones, hypercholersterolemia, oral contraception, oral anticoagulation).
3. History of hypersensitivity to valsartan or HCTZ, inactive ingredients of these study drugs or to drugs with similar chemical structures
4. A history of cardiovascular disease, including angina pectoris, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and peripheral artery disease
5. Known Keith-Wagener grade III or IV hypertensive retinopathy
6. Second or third degree heart block without a pacemaker, concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, clinically significant valvular heart disease
7. Heart failure NYHA II -IV
8. Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, Cushing’s disease, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease
9. Diabetes mellitus type I or diabetes mellitus type II requiring drug treatment
10. Evidence of hepatic disease as determined by AST (SGOT) or ALT (SGPT) values > 2 x ULN at Visit 1, severe liver failure, biliary cirrhosis, cholestasis
11. A history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt
12. Evidence of renal impairment as determined by one of the followings: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome. If creatinine is found to be between 1.5 and 2 x UNL, a retest can be performed prior to initiation of treatment
13. Therapy resistant hypokalaemia, hyponatraemia, hypercalcaemia, or symptomatic hyperuricaemia
14. Any severe, life-threatening disease within the past five years
15. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug.
16. Any surgical or medical condition which, at the discretion of the investigator, places the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period
17. History of drug or alcohol abuse within the last 2 years
18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lifes before enrollment, whichever is longer
19. History of noncompliance with medical regimens, or patients unwilling to comply with the study protocol
20. Persons directly involved in the execution of this protocol/study
21. Inability to communicate and comply with all study requirements
22. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
23. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml).
24. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Detailed analysis of patient adherence is the focus of the primary analysis. Any concomitant therapies reported during the trials will be listed in a table format.
For each patient, the relative time is defined as the time (in days) since date of study entry. For each patient, a longitudinal binary outcome variable Zit will be defined as follows
Zit = 1 if patient i has opened the MEMS monitor exactly once between 07:00 and 11:00 AM on day t.
Zit = 0 otherwise
Comparison of binary time series are realized using logistic regression where dependence among observations from a given patient over time is taken into account through a generalized estimating equation (GEE) approach with a first order autoregressive covariance structure and accounting for the effect of clustering. The effect of intervention will be tested using the above describe model by testing if either the coefficient for GROUP or for the interaction between GROUP and TIME are significantly different from zero. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Supportive measures are blinded for centers not randomized to use of them |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Use / no use of supportive measures |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
Print
