3 x 3 Factorial Trial of Telmisartan and Hydrochlorothiazide in Patients With Essential Hypertension

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00153049
First received: September 9, 2005
Last updated: November 7, 2013
Last verified: November 2013
  Purpose
  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: Telmisartan
Drug: Hydrochlorothiazide
Drug: Telmisartan + Hydrochlorothiazide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blind, Placebo-Controlled, 3 x 3 Factorial Trial of Telmisartan and Hydrochlorothiazide in Patients With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline in supine diastolic blood pressure (DBP) at trough (24 hours post-dose) [ Time Frame: after 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in supine systolic blood pressure (SBP) at trough (24 hours post-dose) [ Time Frame: after 8 weeks ] [ Designated as safety issue: No ]
  • Change in sitting systolic and diastolic blood pressure at trough (24 hours post-dose) [ Time Frame: after 8 weeks ] [ Designated as safety issue: No ]
  • DBP control rate [ Time Frame: after 8 weeks ] [ Designated as safety issue: No ]
  • DBP response rate [ Time Frame: after 8 weeks ] [ Designated as safety issue: No ]
  • SBP response rate [ Time Frame: after 8 weeks ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 583
Study Start Date: June 2004
Estimated Study Completion Date: June 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Essential hypertensive patients who meet the following criteria:

    • Mean supine DBP >= 95 and <= 114 mm Hg at each of Visits 2 and 3.
    • Mean supine DBP must not vary by more than 10 mm Hg between Visit 2 and Visit 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.)

  2. Male or female.
  3. Age >= 20 and Age <= 80 years.
  4. Outpatient.
  5. Able to stop current antihypertensive therapy without risk to the patient.
  6. Ability to provide written Informed Consent in accordance with ?Good Clinical Practice (GCP)? (MHW Ordinance No. 28, as of Mar. 27, 1997) and the local legislation.

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:

    • SGPT(ALT) or SGOT(AST) >= 2 times the upper limit of normal at screening (Visit 1).
    • Patients who have markedly poor bile secretion by the following laboratory parameters: Patients whose direct bilirubin >= 2.0 mg/dL at screening (Visit 1).
    • Serum creatinine >= 2.1 mg/dL at screening (Visit 1).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00153049

Locations
Japan
Boehringer Ingelheim Investigational Site
Annaka, Gunma, Japan, 379-0016
Boehringer Ingelheim Investigational Site
Asahi,Chiba, Japan, 289-2151
Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka, Japan, 814-0163
Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka, Japan, 819-8551
Boehringer Ingelheim Investigational Site
Ichinomiya, Aichi, Japan, 491-0851
Boehringer Ingelheim Investigational Site
Iida,Nagano, Japan, 395-8558
Boehringer Ingelheim Investigational Site
Inzai, Chiba, Japan, 270-1347
Boehringer Ingelheim Investigational Site
Isesaki, Gunma, Japan, 372-0001
Boehringer Ingelheim Investigational Site
Kako-gun, Hyogo, Japan, 675-1112
Boehringer Ingelheim Investigational Site
Kasuya-gun,Fukuoka, Japan, 811-2311
Boehringer Ingelheim Investigational Site
Katsushika-ku,Tokyo, Japan, 124-0006
Boehringer Ingelheim Investigational Site
Kobe, Hyogo, Japan, 651-0072
Boehringer Ingelheim Investigational Site
Koshigaya, Saitama, Japan, 343-0856
Boehringer Ingelheim Investigational Site
Mono-gun, Miyagi, Japan, 981-0503
Boehringer Ingelheim Investigational Site
Osaka, Osaka, Japan, 530-0001
Boehringer Ingelheim Investigational Site
Osaka, Osaka, Japan, 550-0014
Boehringer Ingelheim Investigational Site
Sendai, Miyagi, Japan, 980-8660
Boehringer Ingelheim Investigational Site
Setagun, Gunma, Japan, 377-0061
Boehringer Ingelheim Investigational Site
Shinjyuku, Tokyo, Japan, 160-0022
Boehringer Ingelheim Investigational Site
Shiroishi, Miyagi, Japan, 989-0231
Boehringer Ingelheim Investigational Site
Shiroishi, Miyagi, Japan, 989-0228
Boehringer Ingelheim Investigational Site
Suita, Osaka, Japan, 565-0853
Boehringer Ingelheim Investigational Site
Takasaki, Gunma, Japan, 370-0811
Boehringer Ingelheim Investigational Site
Taya-gun, Gunma, Japan, 370-2132
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Nippon Boehringer Ingelheim Co., Ltd.
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00153049     History of Changes
Other Study ID Numbers: 502.439
Study First Received: September 9, 2005
Last Updated: November 7, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Telmisartan
Hydrochlorothiazide
Telmisartan, hydrochlorothiazide drug combination
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators

ClinicalTrials.gov processed this record on October 19, 2014