Compare Efficacy and Safety of Telmisartan/Hydrochlorothiazide With Telmisartan/Hydrochlorothiazide Plus Amlodipine

An Eight-week Randomised Double-blind Study to Compare the Efficacy and Safety of Telmisartan 80 mg and Amlodipine 5 mg and Hydrochlorothiazide 12.5 mg vs. Telmisartan 80 mg and Hydrochlorothiazide 12.5 mg in Patients With Hypertension Who Fail to Respond Adequately to Treatment With Telmisartan 80 mg and Hydrochlorothiazide 12.5 mg, Followed by a 52 Weeks Extension Study to Assess Long Term Safety of Telmisartan 80 mg and Amlodipine 5 mg and Hydrochlorothiazide 12.5 mg

This is a multi-centre, randomised, double-blind, active-controlled, parallel-group comparative trial to compare the fixed dose combination (FDC) of telmisartan 80 mg + hydrochlorothiazide 12.5 mg and amlodipine 5 mg (T80/A5/H12.5 mg) to telmisartan 80 mg+ hydrochlorothiazide 12.5 mg (T80/H12.5 mg) in blood pressure lowering effect at week 8, the end of the double-blind period in essential hypertensive patients who fail to respond adequately to telmisartan 80 mg+ hydrochlorothiazide 12.5 mg.

Patients are assigned to one of the two groups after a 6-week open-label run-in period taking T80/H12.5 mg.

In addition the long-term safety of telmisartan 80 mg+ amlodipine 5 mg+ hydrochlorothiazide 12.5 mg will be evaluated in a 52-week extension period.

In the 52-week open label extension period patients who are assigned to the T80/A5/H12.5 mg group continue the T80/A5/H12.5 mg therapy, and patients who are assigned to the T80/ /H12.5 mg group change to the T80/A5/H12.5 mg therapy.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: telmisartan + HCTZ; Drug: amlodipine; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiyoda-ku, Tokyo, Japan
    • 1348.2.020 Boehringer Ingelheim Investigational Site
  • Chuo-ku, Fukuoka, Fukuoka, Japan
    • 1348.2.008 Boehringer Ingelheim Investigational Site
  • Chuo-ku,Kobe, Hyogo, Japan
    • 1348.2.018 Boehringer Ingelheim Investigational Site
  • Chuo-ku,Tokyo, Japan
    • 1348.2.006 Boehringer Ingelheim Investigational Site
  • Chuo-ku,Tokyo, Japan
    • 1348.2.013 Boehringer Ingelheim Investigational Site
  • Chuo-ku,Tokyo, Japan
    • 1348.2.021 Boehringer Ingelheim Investigational Site
  • Hirakata, Osaka, Japan
    • 1348.2.012 Boehringer Ingelheim Investigational Site
  • Kasaoka, Okayama, Japan
    • 1348.2.011 Boehringer Ingelheim Investigational Site
  • Kawasaki, Kanagawa, Japan
    • 1348.2.001 Boehringer Ingelheim Investigational Site
  • Kita-ku, Osaka-shi, Osaka, Japan
    • 1348.2.019 Boehringer Ingelheim Investigational Site
  • Kiyota-ku, Sapporo-shi, Hokkaido, Japan
    • 1348.2.014 Boehringer Ingelheim Investigational Site
  • Kumamoto, Kumamoto, Japan
    • 1348.2.002 Boehringer Ingelheim Investigational Site
  • Nakano-ku,Tokyo, Japan
    • 1348.2.007 Boehringer Ingelheim Investigational Site
  • Nishi-ku, Fukuoka, Fukuoka, Japan
    • 1348.2.009 Boehringer Ingelheim Investigational Site
  • Takatsuki, Osaka, Japan
    • 1348.2.005 Boehringer Ingelheim Investigational Site
  • Uji, Kyoto, Japan
    • 1348.2.016 Boehringer Ingelheim Investigational Site
  • Yoshikawa, Saitama, Japan
    • 1348.2.010 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Essential hypertensive patients who have already taking 2 or 3 antihypertensive drugs and mean seated diastolic blood pressure (DBP) must be >=90 and <=114 mmHg and mean seated systolic blood pressure (SBP) must be =<200 mmHg
2. Able to stop all current antihypertensive drugs (other than study medication) from Visit 1b through the end of the trial without risk to the patient based on the investigator's opinion
3. Age 20 years or older

Exclusion criteria:

1. Patients with known or suspected secondary hypertension
2. Patients with clinically relevant cardiac arrhythmia
3. Congestive heart failure with New York Heart Association (NYHA) functional class III-IV
4. Patients with recent cardiovascular events
5. Patients with recent stroke events
6. Patients with a history of sudden deterioration of renal function with angiotensin II receptor blockers or angiotensin converting enzyme inhibitors; or patients with post-renal transplant or post-nephrectomy
7. Patients with hepatic and/or renal dysfunction
8. Pre-menopausal women who are nursing or pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: telmisartan + HCTZ + amlodipine; telmisartan 80 mg + hydrochlorothiazide (HCTZ) 12.5 mg fixed dose combination (FDC) and amlodipine 5 mg capsule (after the 8-week double-blind period, patients will continue the 52-week open label extension period taking 1 telmisartan 80 mg and hydrochlorothiazide 12.5 FDC tablet and 1 amlodipine 5 mg tablet)	Drug: telmisartan + HCTZ; FDC tablet; Drug: amlodipine; capsule
Active Comparator: telmisartan + HCTZ + placebo; telmisartan 80 mg + HCTZ FDC tablet and placebo matching amlodipine 5 mg capsule (after the 8-week double-blind period, patients will continue the 52-week open label extension period taking 1 telmisartan 80 mg and hydrochlorothiazide 12.5 FDC tablet and 1 amlodipine 5 mg tablet)	Drug: telmisartan + HCTZ; FDC tablet; Drug: placebo; placebo matching amlodipine capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period.	Change from baseline in mean seated diastolic blood pressure (DBP) at trough (24-hour post dosing) after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.	baseline and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period.	Change from baseline in mean seated systolic blood pressure (SBP) at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.	baseline and 8 weeks
The Percentage of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 8 Weeks of Double-blind Period.	The percentage of patients with DBP<90 mmHg and SBP<140 mmHg as seated blood pressure at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.	Double-blind and 8 weeks
The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period.	The number of patients with DBP<90 mmHg and SBP<140 mmHg as seated blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.	Reference baseline (week 0) and week 60 (end of extension period)
Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period.	Change from baseline in mean seated diastolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.	Reference baseline (week 0) and week 60 (end of extension period)
Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period.	Change from baseline in mean seated systolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'.	Reference baseline (week 0) and week 60 (end of extension period)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: July 26, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (Estimate): July 30, 2013

Study Record Updates

• Last Update Posted (Estimate): March 28, 2016
• Last Update Submitted That Met QC Criteria: February 26, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Hydrochlorothiazide; Telmisartan
• Other Study ID Numbers: 1348.2