To demonstrate that a fixed dose combination of telmisartan 80 mg plus HCTZ 12.5 mg is superior to telmisartan 80 mg alone in patients, who fail to respond adequately to telmisartan 80 mg monotherapy, in lowering seated trough diastolic blood pressure after eight weeks of treatment.

Condition	Intervention	Phase
Hypertension	Drug: Telmisartan  Drug: Telmisartan/HCTZ	Phase III

Further Study Details: 

Primary Outcomes: The primary efficacy variable is change from baseline in seated DBP at trough (24 hours post-dosing) after eight weeks of randomized treatment or at last trough observation during the double-blind phase (i.e. last trough observation carried forward).
Secondary Outcomes: 1. Change from baseline in seated SBP, standing DBP and SBP at trough after eight weeks of randomized treatment or at last trough observation during the double-blind phase. 2.The percentage of patients responding to the treatment. 3. Sfaty.
Expected Total Enrollment:  244

This is a multi-centre, prospective, randomized, double-blind, parallel-group study in approximately 244 patients with a history of mild-to-moderate hypertensive who have been shown not to respond to telmisartan monotherapy.

All patients will enter a one-week screening phase prior to starting the eight-week open-label T80 mg period. At end of four weeks only patients who fail to respond to T80 mg (DBP >=90 mm Hg) will continue the treatment with T80 mg for another four weeks. At the end of eight weeks, only patients who fail to respond to T80 mg (DBP >= 90 mm Hg) will be randomized, double-blind, to receive either T80 mg alone or the fixed dose combination of T80 mg plus HCTZ 12.5 mg for eight weeks. Seated BP will be taken 24 hours post-dose at each visit. Labs, ECG, and physical examination will be done at screening, at baseline and at the final visit.

Study Hypothesis:

The primary objective of the study, showing that fixed dose combination is superior to telmisartan 80 mg alone will be tested using the hypotheses given below.

H0 : u T80/H12.5 - uT80 = 0 mm Hg vs H1 : uT80/H12.5 - uT80 not equal 0 mm Hg, where uT80/H12.5 anduT80 represent the average reduction from baseline (Visit 4) in trough seated DBP for the fixed dose combination and telmisartan 80 mg, respectively.

Testing of the null hypothesis will be performed using a two-sided test of significance at an a-level (type-I error rate) of 0.05.

Comparison(s):

The primary efficacy endpoint will be the change from baseline in seated DBP 24 hours post-dose at the last visit duirng the double-blind treatment phase. The pre-dose measurement on visit 4 will be viewed as the baseline measurement.

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

1. History of mild-to-moderate hypertension defined by a mean seated DBP >=95 and <=109mmHg before inclusion in the open-label phase 2. Patients who fail to respond adequately to telmisartan monotherapy (mean seated DBP>=90 mmHg ) 3. Participants between 18 and 80 years of age 4. Ability to provide written informed consent Exclusion Criteria

1. Patients taking more than three anti-hypertensive medications at the screening visit.

2. Pre-menopausal women (last menstruation 1 year prior to start of screening):

   1. Who are not surgically sterile (hysterectomy, tubal ligation)
   2. Who are NOT practicing acceptable means of birth control or who do NOT plan to continue using an acceptable method throughout the study. Acceptable methods of birth control include IUD, oral, implantable or injectable contraceptives

3. Any woman:

   1. Who has a positive urine pregnancy test at screening (Visit 1)
   2. Who is nursing

4. Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

   1. SGPT(ALT) or SGOT(AST) greater than two times the upper limit of normal
   2. Serum creatinine >3.0 mg/dL (or 265mol/L) or creatinine clearance <0.6 ml/sec
5. Clinically relevant hypokalaemia or hyperkalaemia
6. Uncorrected volume depletion
7. Uncorrected sodium depletion
8. Primary aldosteronism
9. Hereditary fructose intolerance
10. Biliary obstructive disorders, cholestatis or moderate to severe hepatic insufficiency
11. Known or suspected secondary hypertension
12. Bilateral renal artery stenosis; renal artery stenosis in a solitary kidney; post-renal transplant patients, presence of only one functioning kidney
13. Congestive heart failure (NYHA functional class CHF III-IV
14. Unstable angina within the past three months
15. Stroke within the past six months
16. Myocardial infarction or cardiac surgery within the past three months
17. PTCA within the past three months
18. Patients who have previously experienced symptoms characteristic of angiodema during treatment with ACE inhibitor or angiotensin II receptor antagonists
19. Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator
20. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve
21. Administration of digoxin or other digitalis-type drugs
22. Patients with insulin treated Type II diabetes mellitus whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C >=10%
23. History of drug or alcohol dependency within 6 months prior to enrollment of the study.
24. Concomitant administration of medications known to affect blood pressure, except medications allowed by the protocol
25. Patients receiving any investigational therapy within one month of signing the informed consent form. Patients who have participated in previous telmisartan studies may participate in this study provided there has been at least one month between discontinuing the previous study and signing the consent for the present study
26. Known hypersensitivity to any component of the formulations
27. Any clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of trial medication
28. Concomitant use of lithium or cholestyramine or colestipol resins (potential drug interations with hydrochlorothiazide)

Please refer to this study by ClinicalTrials.gov identifier  NCT00146341

Vivian Gu, Clinical Monitor      +86 (21) 58882200-1127  Ext. 1127    guwei@sha.boehringer-ingelheim.com

China
      254 PLA Hospital, Tianjin,  300150,  China; Recruiting
      Shanghai Ruijin Hospital, Shanghai,  200025,  China; Recruiting
      No. 1 Hospital Affiliated Nanjing, Nanjing,  210006,  China; Recruiting
      No. 1 Hosp Affiliated to Med College, Zhejiang Province,  310003,  China; Recruiting
      Peking Union Medical College Hospital, Beijing,  100730,  China; Recruiting
      China-Japan Friendship Hospital, Beijing,  100029,  China; Recruiting
      Beijing Tiantan Hospital, Beijing,  100050,  China; Recruiting
      Second Hospital Affiliated to Tianjin Med University, Tianjin,  300211,  China; Recruiting
      Shanghai Changhai Hospital, Shanghai,  200433,  China; Recruiting
      No. 6 People''''s Hospital Affiliated to Jiaotong University, Shanghai,  200233,  China; Not yet recruiting
      Shanghai Huadong Hospital, Shanghai,  200040,  China; Not yet recruiting
      Beijing Anzhen Hospital, Beijing,  100029,  China; Not yet recruiting

Study chairs or principal investigators

Vivian Gu, Clinical Monitor,  Study Chair,  Boehringer Ingelheim Shanghai   

Study ID Numbers:  502.472
Last Updated:  September 6, 2005
Record first received:  September 5, 2005
ClinicalTrials.gov Identifier:  NCT00146341
Health Authority: China: State Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13