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A Safety and Tolerability Study of the Combination of Aliskiren/Valsartan in Patients With High Blood Pressure, Followed by Long-term Safety and Tolerability of Aliskiren, Valsartan and Hydrochlorothiazide.

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ClinicalTrials.gov Identifier: NCT00386607
Recruitment Status : Completed
First Posted : October 11, 2006
Results First Posted : May 10, 2011
Last Update Posted : February 10, 2014
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypertension
Interventions Drug: Aliskiren
Drug: Valsartan
Drug: Hydrochlorothiazide (HCTZ)
Enrollment 601
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Core Treatment Extension Treatment
Hide Arm/Group Description Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combiniation for 52-weeks, optional addition of HCTZ 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (msSBP ≥ 140 and/or msDBP ≥ 90 mmHg). The dose of HCTZ 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled.

For patients entering into extension, those previously treated with HCTZ (12.5 or 25 mg) in addition to aliskiren 300 mg/valsartan 320 mg were treated with aliskiren 300 mg/valsartan 320 mg/HCTZ 25 mg in the extension.

Those patients who had not received HCTZ during the core study were treated with aliskiren 300 mg/valsartan 320 mg/HCTZ 12.5 mg.

The HCTZ 12.5 mg dose could be increased to HCTZ 25 mg if the msSBP was ≥140 mmHg and/or the msDBP was ≥90 mmHg for 2 consecutive visits.

Period Title: Core
Started 601 0
Completed 486 0
Not Completed 115 0
Reason Not Completed
Adverse Event             40             0
Abnormal laboratory value(s)             3             0
Unsatisfactory therapeutic effect             23             0
Condition no longer requires study drug             4             0
Patient withdrew consent             15             0
Lost to Follow-up             23             0
Administrative problems             1             0
Protocol Deviation             6             0
Period Title: Extension
Started 0 162
Completed 0 145
Not Completed 0 17
Reason Not Completed
Adverse Event             0             6
Abnormal laboratory value(s)             0             1
Administrative problems             0             1
Lost to Follow-up             0             3
Patient withdrew consent             0             5
Unsatisfactory therapeutic effect             0             1
Arm/Group Title Core Treatment
Hide Arm/Group Description Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combiniation for 52-weeks, optional addition of HCTZ 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (msSBP ≥ 140 and/or msDBP ≥ 90 mmHg). The dose of HCTZ 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled.
Overall Number of Baseline Participants 601
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 601 participants
55.0  (11.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 601 participants
Female
271
  45.1%
Male
330
  54.9%
1.Primary Outcome
Title Overall Percentage of Patients With Adverse Events
Hide Description [Not Specified]
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population: All patients who received at least one dose of Aliskiren/Valsartan
Arm/Group Title Core Treatment- Aliskiren/Valsartan & Aliskiren/Valsartan/HCTZ
Hide Arm/Group Description:
Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combiniation for 52-weeks, optional addition of HCTZ 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (msSBP ≥ 140 and/or msDBP ≥ 90 mmHg). The dose of HCTZ 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled.
Overall Number of Participants Analyzed 601
Measure Type: Number
Unit of Measure: percentage of patients
76.2
2.Primary Outcome
Title Overall Percentage of Patients With Adverse Events
Hide Description adverse event data obtained from both the core study and the 6 month extension study.
Time Frame Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Core and Extension Treatment - Aliskiren/Valsartan/HCTZ
Hide Arm/Group Description:
All patients receiving aliskiren / valsartan / HCTZ during either core or extension study.
Overall Number of Participants Analyzed 310
Measure Type: Number
Unit of Measure: percentage of patients
61.6
3.Secondary Outcome
Title Change From Baseline in Mean Sitting Diastolic Blood Pressure.
Hide Description [Not Specified]
Time Frame Baseline and Weeks 2, 4, 6, 10, 14, 18, 28, 41, and 54
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title Core Treatment
Hide Arm/Group Description:
Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combiniation for 52-weeks, optional addition of HCTZ 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (msSBP ≥ 140 and/or msDBP ≥ 90 mmHg). The dose of HCTZ 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled.
Overall Number of Participants Analyzed 601
Mean (Standard Deviation)
Unit of Measure: mmHg
Week 2 (Visit 5) -7.9  (7.14)
Week 4 (Visit 6) -10.8  (7.83)
Week 6 (Visit 7) -11.8  (8.09)
Week 10 (Visit 8) -12.5  (8.26)
Week 14 (Visit 9) -13.7  (7.87)
Week 18 (Visit 10) -15.0  (8.00)
Week 28 (Visit 11) -15.2  (7.24)
Week 41 (Visit 12) -15.2  (7.60)
Week 54 (Visit 13) -14.2  (7.96)
Endpoint (value at week 54 or LOCF) -13.4  (8.75)
4.Secondary Outcome
Title Change From Baseline in Mean Sitting Systolic Blood Pressure.
Hide Description [Not Specified]
Time Frame Baseline and Weeks 2, 4, 6, 10, 14, 18, 28, 41 and 54
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title Core Treatment
Hide Arm/Group Description:
Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combiniation for 52-weeks, optional addition of HCTZ 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (msSBP ≥ 140 and/or msDBP ≥ 90 mmHg). The dose of HCTZ 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled.
Overall Number of Participants Analyzed 601
Mean (Standard Deviation)
Unit of Measure: mmHg
Week 2 (Visit 5) -11.0  (12.42)
Week 4 (Visit 6) -15.0  (14.03)
Week 6 (Visit 7) -17.6  (14.10)
Week 10 (Visit 8) -18.4  (14.37)
Week 14 (Visit 9) -20.7  (13.42)
Week 18 (Visit 10) -22.6  (14.01)
Week 28 (Visit 11) -24.3  (13.70)
Week 41 (Visit 12) -24.3  (13.27)
Week 54 (Visit 13) -22.3  (14.51)
Endpoint (value at week 54 or LOCF) -20.5  (16.40)
5.Secondary Outcome
Title Percentage of Patients Achieving Blood Pressure Control Target of < 140/90 mmHg
Hide Description [Not Specified]
Time Frame .Weeks 2, 4, 6, 10, 14, 18, 28, 41, and 54
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title Core Treatment
Hide Arm/Group Description:
Oral pills of aliskiren 150 mg /valsartan 160 mg in combination for 2-weeks. The aliskiren 300 mg /valsartan 320 mg in combiniation for 52-weeks, optional addition of HCTZ 12.5 mg starting from Week 10 if the blood pressure was uncontrolled (msSBP ≥ 140 and/or msDBP ≥ 90 mmHg). The dose of HCTZ 12.5 mg could be increased to 25 mg if blood pressure remained uncontrolled.
Overall Number of Participants Analyzed 601
Measure Type: Number
Unit of Measure: Percentage of patients
Week 2 (Visit 5) 32.8
Week 4 (Visit 6) 45.9
Week 6 (Visit 7) 52.4
Week 10 (Visit 8) 60.8
Week 14 (Visit 9) 68.7
Week 18 (Visit 10) 76.4
Week 28 (Visit 11) 77.9
Week 41 (Visit 12) 78.2
Week 54 (Visit 13) 71.7
Endpoint (value at week 54 or LOCF) 66.9
6.Secondary Outcome
Title Change From Baseline in Mean Sitting Diastolic Blood Pressure
Hide Description [Not Specified]
Time Frame Baseline and Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title Extension Treatment
Hide Arm/Group Description:
All patients receiving aliskiren / valsartan / HCTZ in extension study.
Overall Number of Participants Analyzed 179
Mean (Standard Deviation)
Unit of Measure: mmHg
-18.3  (8.52)
7.Secondary Outcome
Title Change From Baseline in Mean Sitting Systolic Blood Pressure
Hide Description [Not Specified]
Time Frame Baseline and Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title Extension Treatment
Hide Arm/Group Description:
All patients receiving aliskiren / valsartan / HCTZ in extension study.
Overall Number of Participants Analyzed 179
Mean (Standard Deviation)
Unit of Measure: mmHg
-28.8  (14.80)
8.Secondary Outcome
Title Percentage of Patients Achieving Blood Pressure Control Target of < 140/90 mmHg in Extension Treatment
Hide Description [Not Specified]
Time Frame Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title Extension Treatment
Hide Arm/Group Description:
All patients receiving aliskiren / valsartan / HCTZ in extension study.
Overall Number of Participants Analyzed 179
Measure Type: Number
Unit of Measure: Percentage of patients
86.6
Time Frame 18 months
Adverse Event Reporting Description All patients who received at least one dose of study medication.
 
Arm/Group Title Core Period: Aliskiren 150 mg / Valsartan 160 mg Alone Core Period: Aliskiren 300 mg / Valsartan 320 mg Alone Core Period: Aliskiren / Valsartan Core and Extension: Aliskiren / Valsartan / HCTZ 12.5 mg Core and Extension: Aliskiren / Valsartan / HCTZ 25 mg Core and Extension: Total
Hide Arm/Group Description Core Period: Aliskiren 150 mg /Valsartan 160 mg alone Core Period: Aliskiren 300 mg /Valsartan 320 mg alone Core Period: Aliskiren/Valsartan Core and Extension: Aliskiren / Valsartan / HCTZ 12.5 mg Core and Extension: Aliskiren/Valsartan/HCTZ 25 mg Core and Extension: Total includes all study patients, treated with Aliskiren/Valsartan or Aliskiren//valsartan/HCTZ during core or extension.
All-Cause Mortality
Core Period: Aliskiren 150 mg / Valsartan 160 mg Alone Core Period: Aliskiren 300 mg / Valsartan 320 mg Alone Core Period: Aliskiren / Valsartan Core and Extension: Aliskiren / Valsartan / HCTZ 12.5 mg Core and Extension: Aliskiren / Valsartan / HCTZ 25 mg Core and Extension: Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Core Period: Aliskiren 150 mg / Valsartan 160 mg Alone Core Period: Aliskiren 300 mg / Valsartan 320 mg Alone Core Period: Aliskiren / Valsartan Core and Extension: Aliskiren / Valsartan / HCTZ 12.5 mg Core and Extension: Aliskiren / Valsartan / HCTZ 25 mg Core and Extension: Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/601 (0.50%)   14/585 (2.39%)   17/601 (2.83%)   3/306 (0.98%)   6/137 (4.38%)   26/601 (4.33%) 
Cardiac disorders             
Acute myocardial infarction  1  1/601 (0.17%)  0/585 (0.00%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Angina pectoris  1  1/601 (0.17%)  0/585 (0.00%)  1/601 (0.17%)  1/306 (0.33%)  0/137 (0.00%)  2/601 (0.33%) 
Cardiac failure  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Myocardial infarction  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Tachycardia  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Ventricular hypokinesia  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Eye disorders             
Retinal vascular thrombosis  1  1/601 (0.17%)  0/585 (0.00%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Gastrointestinal disorders             
Ascites  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
General disorders             
Generalised oedema  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Pain  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Hepatobiliary disorders             
Gallbladder disorder  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Infections and infestations             
Appendicitis  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Clostridium difficile colitis  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Hepatitis B  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Peritoneal abscess  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Injury, poisoning and procedural complications             
Accidental overdose  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Post-traumatic pain  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Subdural haematoma  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Therapeutic agent toxicity  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Thermal burn  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Metabolism and nutrition disorders             
Hypoglycaemia  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Hypokalaemia  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Intervertebral disc protrusion  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Osteoarthritis  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  1/137 (0.73%)  2/601 (0.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Breast cancer  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Malignant melanoma  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  1/306 (0.33%)  0/137 (0.00%)  1/601 (0.17%) 
Nervous system disorders             
Cerebral haemorrhage  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Dizziness  1  1/601 (0.17%)  0/585 (0.00%)  1/601 (0.17%)  0/306 (0.00%)  1/137 (0.73%)  2/601 (0.33%) 
Syncope  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Psychiatric disorders             
Substance abuse  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Respiratory, thoracic and mediastinal disorders             
Asthma  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  1/306 (0.33%)  0/137 (0.00%)  1/601 (0.17%) 
Pulmonary congestion  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Vascular disorders             
Aortic aneurysm  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Deep vein thrombosis  1  0/601 (0.00%)  0/585 (0.00%)  0/601 (0.00%)  0/306 (0.00%)  1/137 (0.73%)  1/601 (0.17%) 
Hypertension  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Hypotension  1  0/601 (0.00%)  1/585 (0.17%)  1/601 (0.17%)  0/306 (0.00%)  0/137 (0.00%)  1/601 (0.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Core Period: Aliskiren 150 mg / Valsartan 160 mg Alone Core Period: Aliskiren 300 mg / Valsartan 320 mg Alone Core Period: Aliskiren / Valsartan Core and Extension: Aliskiren / Valsartan / HCTZ 12.5 mg Core and Extension: Aliskiren / Valsartan / HCTZ 25 mg Core and Extension: Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/601 (8.15%)   185/585 (31.62%)   215/601 (35.77%)   47/306 (15.36%)   26/137 (18.98%)   251/601 (41.76%) 
Gastrointestinal disorders             
Diarrhoea  1  8/601 (1.33%)  27/585 (4.62%)  34/601 (5.66%)  9/306 (2.94%)  1/137 (0.73%)  42/601 (6.99%) 
Infections and infestations             
Bronchitis  1  3/601 (0.50%)  24/585 (4.10%)  27/601 (4.49%)  6/306 (1.96%)  3/137 (2.19%)  34/601 (5.66%) 
Nasopharyngitis  1  6/601 (1.00%)  39/585 (6.67%)  43/601 (7.15%)  10/306 (3.27%)  6/137 (4.38%)  54/601 (8.99%) 
Upper respiratory tract infection  1  2/601 (0.33%)  25/585 (4.27%)  28/601 (4.66%)  9/306 (2.94%)  2/137 (1.46%)  38/601 (6.32%) 
Musculoskeletal and connective tissue disorders             
Back pain  1  4/601 (0.67%)  19/585 (3.25%)  21/601 (3.49%)  5/306 (1.63%)  6/137 (4.38%)  32/601 (5.32%) 
Nervous system disorders             
Dizziness  1  15/601 (2.50%)  39/585 (6.67%)  49/601 (8.15%)  6/306 (1.96%)  7/137 (5.11%)  61/601 (10.15%) 
Headache  1  16/601 (2.66%)  33/585 (5.64%)  45/601 (7.49%)  4/306 (1.31%)  2/137 (1.46%)  50/601 (8.32%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  1/601 (0.17%)  23/585 (3.93%)  24/601 (3.99%)  5/306 (1.63%)  5/137 (3.65%)  31/601 (5.16%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Open label study with no comparator treatment/arm.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00386607     History of Changes
Other Study ID Numbers: CSPV100A2301
CSPV100A2301E1
First Submitted: October 10, 2006
First Posted: October 11, 2006
Results First Submitted: December 20, 2010
Results First Posted: May 10, 2011
Last Update Posted: February 10, 2014