1. To investigate the dose response of the combination therapy, Telmisartan and Hydrochlorothiazide for the Japanese patients with Essential Hypertension.
2. To compare this dose response with that in the US study.

Condition	Intervention	Phase
Hypertension	Drug: Hydrochlorothiazide 12.5 mg  Drug: Hydrochlorothiazide 6.25 mg  Drug: Telmisartan 40 mg  Drug: Telmisartan 40 mg +Hydrochlorothiazide 12.5 mg  Drug: Telmisartan 40 mg +Hydrochlorothiazide 6.25 mg  Drug: Telmisartan 80 mg  Drug: Telmisartan 80 mg +Hydrochlorothiazide 12.5 mg  Drug: Telmisartan 80 mg +Hydrochlorothiazide 6.25 mg	Phase II

Further Study Details: 

Primary Outcomes: Primary endpoint:; The primary efficacy parameter will be change from baseline in supine diastolic; blood pressure (DBP) at trough (24 hours post-dose) at the last visit during the; Double-Blind Period.
Secondary Outcomes: -Change from baseline in supine systolic blood pressure at trough at the last observation during double-blind treatment.; -Change from baseline in sitting systolic and diastolic blood pressure at trough at the last observation during double-blind treatmen
Expected Total Enrollment:  540

This is an 8-week multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group study utilizing all cells of a 3 x 3 factorial design. Following Screening examinations and a 4-week Placebo Run-In Period, 540 patients will be randomized to receive once-daily monotherapy with either telmisartan (MICARDIS®), hydrochlorothiazide, placebo, or combination therapy with telmisartan and hydrochlorothiazide for 8 weeks (Treatment Period).

This study includes nine cells, placebo, telmisartan (TEL) 40 mg, TEL 80 mg, hydrochlorothiazide (HCTZ) 6.25 mg, HCTZ 12.5 mg, TEL 40 mg / HCTZ 6.25 mg, TEL 40 mg / HCTZ 12.5 mg, TEL 80 mg / HCTZ 6.25 mg, and TEL 80 mg / HCTZ 12.5 mg.

Study Hypothesis:

The hypothesis is that the dose response model for the Japanese patient with essential hypertension which is constructed for the change of the supine diastolic blood pressure from the baseline value to end of treatment with the multiple regression analysis, is similar to that in the US study 502.204.

Comparison(s):

The primary efficacy parameter will be the change from baseline in supine diastolic blood pressure at trough (24 hours post-dose) at the last visit during the Double-Blind Period.

The dose response surface model will be constructed. The graphs of dose response surface will be generated based on the final model. The model in this study will compare with that in US study from the perspective of including the same terms in the model.

Ages Eligible for Study:  20 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

Essential hypertensive patients who meet the following criteria.

1. Mean supine DBP >= 95 and <= 114 mm Hg at each of Visits 2 and 3.
2. Mean supine DBP must not vary by more than 10 mm Hg between Visit 2 and Visit 3.
3. Mean supine systolic blood pressure (SBP) must be >= 140 and <= 200 mm Hg at Visit 3.

The mean DBP and SBP values are calculated as the mean of the three supine measurements taken two minutes apart.

Exclusion Criteria:

1. Known or suspected secondary hypertension (renovascular hypertension, primary aldosteronism, melanocytoma, etc.).
2. Mean supine DBP > 114 mmHg and/or mean supine SBP > 200 mmHg during any visit of the placebo run-in period.
3. Sustained ventricular tachycardia or other clinically relevant cardiac arrhythmias (atrioventricular conduction disturbance (grade II - III), atrial fibrillation etc.).
4. NYHA functional class heart failure III-IV.
5. Myocardial infarction or cardiac surgery within 6 months of signing the informed consent form.
6. Coronary artery bypass surgery or percutaneous transluminal coronary angioplasty (PTCA) within 3 months of signing the informed consent form.
7. Unstable angina within 3 months of signing the informed consent form.
8. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of aortic or mitral valve.
9. Stroke or transient ischemic attack within 6 months of signing the informed consent form.
10. History of sudden exacerbation of renal function with AT1 receptor antagonists or ACE inhibitors; post-renal transplant.
11. Patients who have previously experienced characteristic symptoms of angioedema (such as facial, tongue, pharyngeal, laryngeal swelling with dyspnea) during treatment with AT1 receptor antagonists or ACE inhibitors.
12. Known hypersensitivity to any component of the formulation, or a known hypersensitivity to sulfonamides or sulphonamide-derived drugs (e.g. thiazides).
13. Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

1) SGPT(ALT) or SGOT(AST) >= 2 times the upper limit of normal at screening (Visit 1) 2) Patients who have markedly poor bile secretion by the following laboratory parameters: Patients whose direct bilirubin >= 2.0 mg/dL at screening (Visit 1) 3) Serum creatinine >= 2.1 mg/dL at screening (Visit 1) 14. Clinically significant sodium depletion as defined by serum sodium level less than 130 mEq/L (Visit 1); clinically significant hyperkalemia as defined by serum potassium level > 6.0 mEq/L (Visit 1). Clinically significant hypokalemia as defined by serum potassium level < 3.0 mEq/L (Visit 1).

15. Known, suspected or history of gout; hyperuricemia (serum uric acid >= 8.0 mg/dL at screening (Visit 1) regardless of treatment).

16. Evidence of significant retinal hemorrhages/exudates/ papilledema. 17.Type I diabetes mellitus; Type II diabetes mellitus requiring the use of oral hypoglycemics.

18. Administration of medications known to affect blood pressure. 19. Chronic administration of high doses of acidic NSAIDs (oral medication, suppository and injection) (e.g., ibuprofen for rheumatoid arthritis and osteoarthritis in total daily dose in excess of 600 mg as upper limit of the approval dosage).

20. Chronic administration of high doses of acetaminophen (e.g., total daily dose in excess of 1.5 G per day as upper limit of the approval dosage).

21. Chronic use of salt substitutes containing potassium chloride; extreme dietary restrictions.

22. Pre-menopausal women who meet any one of the following 1) - 3):

1. Pregnant or possibly pregnant
2. Nursing
3. Desire to be pregnant during study period Even when a patient was confirmed not to fall under the criteria above at initiation of study, if the patient is of childbearing potential, pregnancy tests should be performed when possible. If pregnancy is turned out, the investigational product should be discontinued.

23. Known drug or alcohol dependency. 24. Complication of malignant tumour or a disease requiring oral or injection immunosuppressants. 25. Compliance of < 80% or > 120% during the Placebo Run-In Period. 26. Patients receiving any investigational therapy within 3 months of signing the informed consent form.

27. Any other clinical condition which, in the opinion of the principal investigator, would not allow safe completion of the protocol and safe administration of trial

Japan
      ToCROM Clinic, Shinjyuku, Tokyo,  160-0022,  Japan
      Uchino Clinic, Inzai, Chiba,  270-1347,  Japan
      Fukuoka Hara Rehabilitation Hospital, Fukuoka, Fukuoka,  819-8551,  Japan
      OCROM Clinic, Suita, Osaka,  565-0853,  Japan
      Makabe Hospital, Mono-gun, Miyagi,  981-0503,  Japan
      Sato Hospital, Sendai, Miyagi,  980-8660,  Japan
      Yamaki Clinic, Shiroishi, Miyagi,  989-0228,  Japan
      Katta Public General Hospital, Shiroishi, Miyagi,  989-0231,  Japan
      Sakurabashi Watanabe Hospital, Osaka, Osaka,  530-0001,  Japan
      Kitahorie Hospital, Osaka, Osaka,  550-0014,  Japan
      Koshigaya Seiwa Hospital, Koshigaya, Saitama,  343-0856,  Japan
      Muta Hospital, Fukuoka, Fukuoka,  814-0163,  Japan
      Matsumoto Clinic, Takasaki, Gunma,  370-0811,  Japan
      Shoda Hospital, Annaka, Gunma,  379-0016,  Japan
      Yoshii Central Clinic, Taya-gun, Gunma,  370-2132,  Japan
      Hikari Clinic, Kako-gun, Hyogo,  675-1112,  Japan
      Fukuoka Seisyukai Hospital, Kasuya-gun,Fukuoka,  811-2311,  Japan
      Shinkatsushika Royal Clinic, Katsushika-ku,Tokyo,  124-0006,  Japan
      Kizankai Memorial Hospital, Iida,Nagano,  395-8558,  Japan
      National Asahi Central Hospital, Asahi,Chiba,  289-2151,  Japan
      Daiyukai Clinic, Ichinomiya, Aichi,  491-0851,  Japan
      Shinko Hospital, Kobe, Hyogo,  651-0072,  Japan
      Cardiovascular Hospital of Central Japan, Setagun, Gunma,  377-0061,  Japan
      Ishii Hospital, Isesaki, Gunma,  372-0001,  Japan

Study chairs or principal investigators

Yoko Seki,  Study Chair,  Nippon Boehringer/Kawanishi   

Study ID Numbers:  502.439
Last Updated:  September 9, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00153049
Health Authority: Japan: Ministry of Health, Labor and Welfare
ClinicalTrials.gov processed this record on 2005-09-13