Hydrochlorothiazide as add-on to Olmesartan/Amlodipine in Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00902538
First received: May 13, 2009
Last updated: February 20, 2012
Last verified: February 2012
  Purpose

Both Olmesartan (OLM)/Amlodipine (AML) combination and Hydrochlorothiazide (HCTZ) have proven to be efficacious and safe in lowering blood pressure, but may not always be sufficient. This study is to test efficacy and safety of the combination of OLM/AML and HCTZ in hypertensive patients whose blood pressure is not adequately controlled with OLM/AML alone. The following treatments will be included in the trial: OLM 40mg/AML 10mg; OLM 40mg/AML 10 mg/HCTZ 12.5 mg; OLM 40 mg/AML 10 mg/HCTZ 25 mg. The trial has four periods. The treatments that will be used are as follows:

Period 1 - OLM 40mg/AML 10mg; Period 2 - OLM 40mg/AML 10mg or OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg; Period 3 - OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 non-responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg


Condition Intervention Phase
Essential Hypertension
Drug: Olmesartan medoxomil 40 mg - Amlodipine 10 mg
Drug: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg
Drug: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg
Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg
Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Add-on Study of Hydrochlorothiazide in Patients With Moderate to Severe Hypertension Not Achieving Target Blood Pressure on Olmesartan/Amlodipine Alone

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg [ Time Frame: baseline (8 weeks) to 16 weeks ] [ Designated as safety issue: No ]
    Three cuff blood pressure measurements were taken at each visit.


Secondary Outcome Measures:
  • Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg [ Time Frame: baseline (8 weeks) to week 16 ] [ Designated as safety issue: No ]
    Three cuff blood pressure measurements were taken at each visit.

  • Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16. [ Time Frame: baseline (week 8) to week 16 ] [ Designated as safety issue: No ]
    Achieving blood pressure goal is defined as seated blood pressure <140/90 mm Hg; 130/80 mm Hg for participants with diabetes and/or other chronic renal and/or chronic cardiovascular disease. Three cuff blood pressure measurements were taken at each visit.

  • Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM). [ Time Frame: Baseline (8 weeks) to 16 weeks ] [ Designated as safety issue: No ]
    Three cuff blood pressure measurements were taken at each visit.

  • Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. [ Time Frame: Baseline (8 weeks) to 16 weeks ] [ Designated as safety issue: No ]
    Three cuff blood pressure measurements were taken at each visit.

  • In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. [ Time Frame: week 24 to week 32 ] [ Designated as safety issue: No ]
    Change in seated diastolic blood pressure from the beginning to the end of Period 4. Three cuff blood pressure measurements were taken at each visit.

  • In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. [ Time Frame: week 24 to week 32 ] [ Designated as safety issue: No ]
    Change in seated systolic blood pressure from the beginning to the end of Period 4. Three cuff blood pressure measurements were taken at each visit.

  • In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. [ Time Frame: week 24 to week 32 ] [ Designated as safety issue: No ]
    The number of non-responding participants who achieved their blood pressure goals at the end of Period 4. Achieving blood pressure goal is defined as seated blood pressure <140/90 mm Hg; 130/80 mm Hg for participants with diabetes and/or other chronic renal and/or chronic cardiovascular disease. Three cuff blood pressure measurements were taken at each visit.

  • In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. [ Time Frame: Week 16 to week 32 ] [ Designated as safety issue: No ]
    In non-responders, the change in 24-hour diastolic blood pressure assessed by 24-hour ambulatory blood pressure measurement from the beginning to the end of Period 4.

  • In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. [ Time Frame: Week 16 to week 32 ] [ Designated as safety issue: No ]
    In non-responders, the change in 24-hour systolic blood pressure assessed by 24-hour ambulatory blood pressure measurement from the beginning to the end of Period 4.


Enrollment: 2204
Study Start Date: April 2009
Study Completion Date: October 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olmesartan (OLM) 40mg-Amlodipine (AML) 10mg
The participants in this arm received these 2 drugs for the 8-week, single-blind, run-in Period 1. Participants could then randomized to this same combination for an additional 8 weeks in the double-blind, Period 2.
Drug: Olmesartan medoxomil 40 mg - Amlodipine 10 mg
Oral tablets containing Olmesartan medoxomil-Amlodipine 40-10 mg, given once daily
Experimental: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg
Participants could start receiving this combination in randomized, double-blind, 8-week Period 2. This combination was continued into single-blind, 8-week Period 3 for all participants entering Period 3.
Drug: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
Experimental: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg
Participants could start receiving this combination in randomized, double-blind, 8- week Period 2.
Drug: Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablets. All tablets are given once a day.
Other Name: Olmesartan 40mg-Amlodipine 10mg tablet + 2 Hydrochlorothiazide 12.5mg tablets
Experimental: OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg (Responders)
Participants who meet their blood pressure goals in Period 3 and continued into the 8-week, double-blind Period 4 continued to receive this combination.
Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
Experimental: OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg (Non-responders)
Participants finishing Period 3, but, who did not meet their blood pressure goals could receive this combination in the double-blind, randomized, Period 4
Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
Experimental: OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg (Non-responders)
Participants finishing Period 3, but, who did not meet their blood pressure goals could receive this combination in the double-blind, randomized, Period 4
Drug: OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablet. All tablets are given once a day.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged 18 years or older.
  • Mean trough seated systolic blood pressure (SeSBP) of ≥ 160/100 mmHg (SeSBP of ≥ 160 mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at screening if not currently on antihypertensive medication (e.g. newly diagnosed subjects)

OR:

For subjects on monotherapy: mean trough SeSBP of ≥ 150/95 mmHg (SeSBP of ≥ 150 mmHg and SeDBP ≥ 95 mmHg) at screening

OR:

For subjects on any combination of antihypertensive medications that includes either hydrochlorothiazide or amlodipine or olmesartan for a duration of at least four weeks: mean trough SeSBP of ≥ 140/90 mmHg (SeSBP of ≥ 140 mmHg and SeDBP ≥ 90 mmHg) at screening

OR:

For subjects on any other combination of antihypertensive medications that includes neither hydrochlorothiazide, amlodipine nor olmesartan: mean trough SeSBP ≥ 160 mmHg, mean trough SeDBP ≥ 100mmHg, at the end of the taper-off period

  • Subject freely signs the Informed Consent Form (ICF) after the nature of the study and the disclosure of his/her data has been explained.
  • Female subjects of childbearing potential must be using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study [Visit 1]). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable), and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If a female becomes pregnant during the study, she has to be withdrawn immediately.

Exclusion Criteria:

  • Female subjects of childbearing potential who are pregnant or lactating.
  • Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of the investigational products, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic subjects.
  • Subjects having a history of the following within the last six months: myocardial infarction (MI), unstable angina pectoris, percutaneous coronary intervention, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischaemic attack.
  • Subjects with clinically significant abnormal laboratory values at Screening, including subjects with one or more of the following:

    • Aspartate aminotransferase (AST) > 3 times upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) > 3 times ULN
    • Gamma-glutamyltransferase (GGT) > 3 times ULN
    • Potassium above ULN (unless high value is due to haemolytic blood sample)
  • Subjects with secondary hypertension of any aetiology such as renal disease, phaeochromocytoma, or Cushing's syndrome.
  • Subjects with contraindication to olmesartan, amlodipine, hydrochlorothiazide, or any of the excipients.
  • Subjects with a mean SeSBP > 200 mmHg or mean SeDBP > 115 mmHg or bradycardia (heart rate < 50 beats/min at rest documented by mean radial pulse rate [PR] or electrocardiogram [ECG]) at Screening (Visit 1) or immediately before taking Period I study medication (Visit 2).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00902538

  Show 117 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT00902538     History of Changes
Other Study ID Numbers: CS8635-A-E303
Study First Received: May 13, 2009
Results First Received: September 6, 2011
Last Updated: February 20, 2012
Health Authority: Austria: Federal Office for Safety in Health Care
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Daiichi Sankyo Inc.:
Add on treatment
essential hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Olmesartan
Olmesartan medoxomil
Amlodipine
Hydrochlorothiazide
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on September 18, 2014