Antihypertensive Efficacy and Safety of Candesartan/HCT 32/25 mg in Comparison With Individual Components and Placebo

• ClinicalTrials.gov Identifier: NCT00434967
• Recruitment Status: Completed
• First Posted: February 14, 2007
• Results First Posted: June 17, 2009
• Last Update Posted: December 16, 2010
• Sponsor: AstraZeneca
• Information provided by: AstraZeneca

Tracking Information

• First Submitted Date: February 13, 2007
• First Posted Date: February 14, 2007
• Results First Submitted Date: January 9, 2009
• Results First Posted Date: June 17, 2009
• Last Update Posted Date: December 16, 2010
• Study Start Date: January 2007
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2009)

• Change in Sitting Diastolic Blood Pressure (DBP) From Baseline to the End of the Study (From Baseline to 8 Weeks). [ Time Frame: 8 weeks ]
  Change (reduction) in sitting DBP at the end of the study, when compared to sitting DBP at baseline.
• Change in Sitting Systolic Blood Pressure (SBP) From Baseline to the End of the Study (Baseline to 8 Weeks) [ Time Frame: 8 weeks ]
  Change (reduction) in sitting SBP at the end of the study, when compared to sitting SBP at baseline.

• Original Primary Outcome Measures (submitted: February 13, 2007): Change (reduction) in sitting BP (24 hours after dose) from baseline (randomisation) to the end of the study.

Current Secondary Outcome Measures (submitted: April 29, 2009)

• The Number of Patients With Controlled Sitting DBP and Sitting SBP in Each Treatment Group at the End of the Study [ Time Frame: 8 weeks ]
  Controlled sitting SBP and sitting DBP are defined as having sitting SBP < 140 mmHg and sitting DBP < 90 mmHg at the end of the study
• Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Hypertension Control Rate at the End of the Study (Patients With Controlled Sitting SBP and Sitting DBP). [ Time Frame: Baseline to 8 weeks ]
• To Describe Safety and Tolerability of the Study Treatments With Regard to Adverse Events Including Those That Lead to Treatment Discontinuation as Well as With Regard to Pulse Rate, Laboratory, Electrocardiographic and Physical Examination Findings. [ Time Frame: Baseline to 8 weeks ]
• To Compare Treatment With Candesartan/HCT 32/25 mg to Each of Its Components With Regard to Change From Baseline to Week 8 in Standing DBP and Standing SBP. [ Time Frame: Baseline to 8 weeks ]
• To Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Sitting DBP Control Rate at the End of the Study (Patients With Controlled Sitting DBP Are Defined as Having a Sitting DBP <90 mmHg at the End of the Study). [ Time Frame: Baseline to 8 weeks ]
• To Compare Candesartan/HCT 32/25 mg to Its Components and to Placebo With Regard to Sitting DBP Responder Rate (Decrease in Sitting DBP ≥10 mmHg From Baseline to the End of the Study or a Sitting DBP <90 mmHg at the End of the Study). [ Time Frame: Baseline to 8 weeks ]

Original Secondary Outcome Measures (submitted: February 13, 2007)

• Proportion of patients with controlled sitting BP in each treatment group at the end of the study.
• Occurrence of Adverse Events and discontinuation of study medication due to AEs from baseline (randomisation) to the end of the study.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Antihypertensive Efficacy and Safety of Candesartan/HCT 32/25 mg in Comparison With Individual Components and Placebo
• Official Title: A Double-blind, Randomised, 4-arm Parallel Group, Multicentre, 8-week, Phase III Study to Assess the Antihypertensive Efficacy and Safety of the Combination of Candesartan Cilexetil (CC) 32 mg and Hydrochlorothiazide (HCT) 25 mg Compared With CC 32 mg, HCT 25 mg and Placebo in Hypertensive Adults
• Brief Summary: The aim is to compare the blood pressure lowering effect of the combination of candesartan cilexetil (candesartan) 32 mg and hydrochlorothiazide (HCT) 25 mg to that of candesartan 32 mg alone, HCT 25 mg alone and placebo in hypertensive adults.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: Candesartan cilexetil
  32 mg oral tablet
  Other Name: ATACAND
• Drug: Hydrochlorothiazide
  25 mg oral tablet
  Other Name: HCTZ
• Drug: Candesartan/HCT 32/25 mg

Study Arms

• No Intervention: 4
  Placebo
• Active Comparator: 2
  Candesartan cilexetil
  Intervention: Drug: Candesartan cilexetil
• Active Comparator: 3
  Hydrochlorothiazide (HCT)
  Intervention: Drug: Hydrochlorothiazide
• Experimental: 1
  Candesartan cilexetil + Hydrochlorothiazide Combination
  Interventions:

  • Drug: Candesartan cilexetil
  • Drug: Hydrochlorothiazide
  • Drug: Candesartan/HCT 32/25 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 29, 2009): 2207
• Original Enrollment (submitted: February 13, 2007): 1200
• Actual Study Completion Date: January 2008
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients will be eligible for enrolment into the study (Visit 1) if they fulfil all of the following criteria:
• Provision of signed Informed Consent
• Primary hypertension, untreated or treated with a maximum of 2 antihypertensive drugs (substances), which the patient and the physician are willing to withdraw at enrolment and replace with placebo.
• Mean sitting DBP 90-114 mmHg (value calculated in the eCRF) at Visits 1 and 2
• Patients will be eligible for randomisation (Visit 4) if they fulfil the following criterion:
• Mean sitting DBP of 90-114 mmHg (value calculated in the eCRF) at the end of the 4-week single-blind placebo run-in period. The run-in period should not be shorter than 4 weeks.

Exclusion Criteria:

• Pregnant or lactating women, or women of childbearing potential not practising an adequate method of contraception eg, intrauterine device, oral contraception or progesterone implant. Pregnancy must be excluded by a negative pregnancy test at Visit 1.
• Secondary or malignant hypertension
• Sitting SBP of 180 mmHg or more
• Myocardial infarction, stroke, coronary bypass surgery or transient ischaemic attack within 6 months before enrolment
• Angina pectoris requiring more treatment than short-acting nitrates
• Chronic use of NSAIDs
• Aortic or mitral valve stenosis
• Cardiac failure requiring treatment
• Cardiac arrhythmia requiring treatment
• Gout
• Renal artery stenosis or kidney transplantation
• Intravascular volume depletion
• Hypersensitivity to any component of the investigational products or to any sulphonamide derived drugs
• Concomitant disease which may interfere with the assessment of the patient
• Past or present alcohol or drug abuse, or any condition associated with poor compliance that in the opinion of the investigator might affect the patient's participation in the study
• Chronic liver disease
• Concomitant or previous treatment with any other investigational drug within 20 days of enrolment
• Previous enrolment in the present study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Latvia, Malta, Romania, Russian Federation, Slovakia

Administrative Information

• NCT Number: NCT00434967
• Other Study ID Numbers: D2456C00002; EudraCT No. 2006-003963-30
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Michael Klibaner, MD; AstraZeneca
• Principal Investigator: Istvan Edes, MD; DEOEC Institute of Cardiology

• PRS Account: AstraZeneca
• Verification Date: November 2010