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

Primary Purpose

Hypertension

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Telmisartan
Hydrochlorothiazide
Telmisartan + Hydrochlorothiazide
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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.) Male or female. Age >= 20 and Age <= 80 years. Outpatient. Able to stop current antihypertensive therapy without risk to the patient. 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: Known or suspected secondary hypertension (renovascular hypertension, primary aldosteronism, melanocytoma, etc.). Mean supine DBP > 114 mmHg and/or mean supine SBP > 200 mmHg during any visit of the placebo run-in period. Sustained ventricular tachycardia or other clinically relevant cardiac arrhythmias (atrioventricular conduction disturbance (grade II - III), atrial fibrillation etc.). NYHA functional class heart failure III-IV. Myocardial infarction or cardiac surgery within 6 months of signing the informed consent form. Coronary artery bypass surgery or percutaneous transluminal coronary angioplasty (PTCA) within 3 months of signing the informed consent form. Unstable angina within 3 months of signing the informed consent form. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of aortic or mitral valve. Stroke or transient ischemic attack within 6 months of signing the informed consent form. History of sudden exacerbation of renal function with AT1 receptor antagonists or ACE inhibitors; post-renal transplant. 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. Known hypersensitivity to any component of the formulation, or a known hypersensitivity to sulfonamides or sulphonamide-derived drugs (e.g. thiazides). 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).

Sites / Locations

  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site
  • Boehringer Ingelheim Investigational Site

Outcomes

Primary Outcome Measures

Change from baseline in supine diastolic blood pressure (DBP) at trough (24 hours post-dose)

Secondary Outcome Measures

Change in supine systolic blood pressure (SBP) at trough (24 hours post-dose)
Change in sitting systolic and diastolic blood pressure at trough (24 hours post-dose)
DBP control rate
DBP response rate
SBP response rate
Incidence of adverse events

Full Information

First Posted
September 9, 2005
Last Updated
November 7, 2013
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT00153049
Brief Title
3 x 3 Factorial Trial of Telmisartan and Hydrochlorothiazide in Patients With Essential Hypertension
Official Title
A Randomised, Double-Blind, Placebo-Controlled, 3 x 3 Factorial Trial of Telmisartan and Hydrochlorothiazide in Patients With Essential Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
June 2004 (undefined)
Primary Completion Date
June 2005 (Actual)
Study Completion Date
June 2005 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
Double
Allocation
Randomized
Enrollment
583 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Telmisartan
Intervention Type
Drug
Intervention Name(s)
Hydrochlorothiazide
Intervention Type
Drug
Intervention Name(s)
Telmisartan + Hydrochlorothiazide
Primary Outcome Measure Information:
Title
Change from baseline in supine diastolic blood pressure (DBP) at trough (24 hours post-dose)
Time Frame
after 8 weeks
Secondary Outcome Measure Information:
Title
Change in supine systolic blood pressure (SBP) at trough (24 hours post-dose)
Time Frame
after 8 weeks
Title
Change in sitting systolic and diastolic blood pressure at trough (24 hours post-dose)
Time Frame
after 8 weeks
Title
DBP control rate
Time Frame
after 8 weeks
Title
DBP response rate
Time Frame
after 8 weeks
Title
SBP response rate
Time Frame
after 8 weeks
Title
Incidence of adverse events
Time Frame
up to 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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.) Male or female. Age >= 20 and Age <= 80 years. Outpatient. Able to stop current antihypertensive therapy without risk to the patient. 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: Known or suspected secondary hypertension (renovascular hypertension, primary aldosteronism, melanocytoma, etc.). Mean supine DBP > 114 mmHg and/or mean supine SBP > 200 mmHg during any visit of the placebo run-in period. Sustained ventricular tachycardia or other clinically relevant cardiac arrhythmias (atrioventricular conduction disturbance (grade II - III), atrial fibrillation etc.). NYHA functional class heart failure III-IV. Myocardial infarction or cardiac surgery within 6 months of signing the informed consent form. Coronary artery bypass surgery or percutaneous transluminal coronary angioplasty (PTCA) within 3 months of signing the informed consent form. Unstable angina within 3 months of signing the informed consent form. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of aortic or mitral valve. Stroke or transient ischemic attack within 6 months of signing the informed consent form. History of sudden exacerbation of renal function with AT1 receptor antagonists or ACE inhibitors; post-renal transplant. 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. Known hypersensitivity to any component of the formulation, or a known hypersensitivity to sulfonamides or sulphonamide-derived drugs (e.g. thiazides). 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim Study Coordinator
Organizational Affiliation
Nippon Boehringer Ingelheim Co., Ltd.
Official's Role
Study Chair
Facility Information:
Facility Name
Boehringer Ingelheim Investigational Site
City
Annaka, Gunma
ZIP/Postal Code
379-0016
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Asahi,Chiba
ZIP/Postal Code
289-2151
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Fukuoka, Fukuoka
ZIP/Postal Code
814-0163
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Fukuoka, Fukuoka
ZIP/Postal Code
819-8551
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Ichinomiya, Aichi
ZIP/Postal Code
491-0851
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Iida,Nagano
ZIP/Postal Code
395-8558
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Inzai, Chiba
ZIP/Postal Code
270-1347
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Isesaki, Gunma
ZIP/Postal Code
372-0001
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Kako-gun, Hyogo
ZIP/Postal Code
675-1112
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Kasuya-gun,Fukuoka
ZIP/Postal Code
811-2311
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Katsushika-ku,Tokyo
ZIP/Postal Code
124-0006
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Kobe, Hyogo
ZIP/Postal Code
651-0072
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Koshigaya, Saitama
ZIP/Postal Code
343-0856
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Mono-gun, Miyagi
ZIP/Postal Code
981-0503
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Osaka, Osaka
ZIP/Postal Code
530-0001
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Osaka, Osaka
ZIP/Postal Code
550-0014
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Sendai, Miyagi
ZIP/Postal Code
980-8660
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Setagun, Gunma
ZIP/Postal Code
377-0061
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Shinjyuku, Tokyo
ZIP/Postal Code
160-0022
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Shiroishi, Miyagi
ZIP/Postal Code
989-0228
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Shiroishi, Miyagi
ZIP/Postal Code
989-0231
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Suita, Osaka
ZIP/Postal Code
565-0853
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Takasaki, Gunma
ZIP/Postal Code
370-0811
Country
Japan
Facility Name
Boehringer Ingelheim Investigational Site
City
Taya-gun, Gunma
ZIP/Postal Code
370-2132
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
17389151
Citation
Horie Y, Higaki J, Takeuchi M. Design, statistical analysis and sample size calculation of dose response study of telmisartan and hydrochlorothiazide. Contemp Clin Trials. 2007 Sep;28(5):647-53. doi: 10.1016/j.cct.2007.02.005. Epub 2007 Feb 27.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/502/502.439_U06-3030.pdf
Description
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3 x 3 Factorial Trial of Telmisartan and Hydrochlorothiazide in Patients With Essential Hypertension

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