Effects of Aliskiren and Amlodipine on the Renin-Angiotensin System (RAS) and Lipid/Carbohydrate Metabolism in Obese Patients With Hypertension

This study has been terminated.
(Early termination resulted from interim analysis of the ALTITUDE trial)
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00498433
First received: July 8, 2007
Last updated: October 23, 2013
Last verified: October 2013
Results First Received: March 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Hypertension
Abdominal Obesity
Interventions: Drug: Aliskiren
Drug: Amlodipine
Drug: Placebo of Aliskiren
Drug: Placebo of amlodipine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Total 46 patients entered into the study; 10 patients in part 1 received study drug. 36 patients enrolled into part 2 and and 16 patients received study drug.

Reporting Groups
  Description
Placebo

Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase.

Part 2, Period 1: After confirming study eligibility based on inclusion and exclusion criteria, patients underwent a two week single-blind placebo run-in phase.

Aliskiren

Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d..

Part 2, Double Blind Period: Eligible randomized patients received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks

Amlodipine

Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.

Part 2, Double Blind Period: Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks


Participant Flow for 5 periods

Period 1:   Part 1, Period 1:Placebo Run-in(2 Weeks)
    Placebo     Aliskiren     Amlodipine  
STARTED     10     0     0  
COMPLETED     10     0     0  
NOT COMPLETED     0     0     0  

Period 2:   Part 1, Period 2: Aliskiren (4 Weeks)
    Placebo     Aliskiren     Amlodipine  
STARTED     0     10     0  
COMPLETED     0     10     0  
NOT COMPLETED     0     0     0  

Period 3:   Part 1, Period 3: Amlodipine (4-8 Weeks)
    Placebo     Aliskiren     Amlodipine  
STARTED     0     0     10  
COMPLETED     0     0     10  
NOT COMPLETED     0     0     0  

Period 4:   Part 2: Placebo Run-in (2 Weeks)
    Placebo     Aliskiren     Amlodipine  
STARTED     36     0 [1]   0 [1]
COMPLETED     16     0     0  
NOT COMPLETED     20     0     0  
Adverse Event                 2                 0                 0  
Abnormal laboratory value                 2                 0                 0  
Abnormal test procedure                 15                 0                 0  
Administrative problems                 1                 0                 0  
[1] For part 2, this arm belongs to randomized, double blind period.

Period 5:   Part 2: Double Blind (12 Weeks)
    Placebo     Aliskiren     Amlodipine  
STARTED     0     8     8  
COMPLETED     0     8     8  
NOT COMPLETED     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Part 1 : Baseline measures are on all patients.

Part 2: Randomized population of double-blind period used for Baseline/Demographic measurements.


Reporting Groups
  Description
Part 1: Placebo/Aliskiren/Amlodipine

Part 1, Period 1: After a 1-2 weeks initial washout period, all eligible patients underwent a two week placebo run-in phase.

Part 1 , Period 2: All eligible patients received 4 week treatment of 300 mg aliskiren o.d..

Part 1, Period 3: All patients received 5 mg amlodipine o.d.. The length of the amlodipine period varied from 4 to 7 weeks.

Part 2, Double Blind Period: Aliskiren Eligible randomized patients received aliskiren 300 mg tablet o.d. and amlodipine placebo capsule o.d. for 12 weeks
Part 2, Double Blind: Amlodipine Eligible randomized patients received amlodipine 5 mg o.d. and aliskiren placebo o.d. for 12 weeks
Total Total of all reporting groups

Baseline Measures
    Part 1: Placebo/Aliskiren/Amlodipine     Part 2, Double Blind Period: Aliskiren     Part 2, Double Blind: Amlodipine     Total  
Number of Participants  
[units: participants]
  10     8     8     26  
Age  
[units: years]
Mean ± Standard Deviation
       
Part 1, Open Label     46  ± 7.5     NA  ± NA [1]   NA  ± NA [1]   46  ± 7.5  
Part 2, Double blind     NA  ± NA [2]   46.0  ± 10.92     49.4  ± 10.53     47.7  ± 10.17  
Gender  
[units: participants]
       
Female     2     2     2     6  
Male     8     6     6     20  
[1] This arm is used for part 2, double blind period
[2] This arm is used for part 1, open label .



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Part 1: Aliskiren Concentrations From Interstitial Fluid (Microdialysis)at the End of Aliskiren Treatment Period   [ Time Frame: Day 42 ]

2.  Primary:   Part 1: Amlodipine Concentrations From Interstitial Fluid (Microdialysis) at the End of Amlodipine Treatment Period   [ Time Frame: Day 98 ]

3.  Primary:   Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Aliskiren Treatment Period   [ Time Frame: Day 42 ]

4.  Primary:   Part 1: Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Amlodipine Treatment Period   [ Time Frame: Day 98 ]

5.  Primary:   Part 1: Aliskiren Concentrations From Tissue at the End of Aliskiren Treatment Period   [ Time Frame: Day 42 ]

6.  Primary:   Part 1: Angiotensin II Levels From Tissue During Aliskiren Treatment Period   [ Time Frame: Day 42 ]

7.  Primary:   Part 1: Renin Activity and Concentrations From Adipose and Skeletal Tissues During Aliskiren Treatment Period   [ Time Frame: Day 42 ]

8.  Primary:   Part 1: Aliskiren Concentrations From Plasma at the End of Aliskiren Treatment Period   [ Time Frame: Day 42 ]

9.  Primary:   Part 1: Amlodipine Concentrations From Plasma at the End of Amlodipine Treatment Period   [ Time Frame: Day 98 ]

10.  Primary:   Part 1: Angiotensin II Levels in Plasma During Aliskiren Treatment Period   [ Time Frame: Day 42 ]

11.  Primary:   Part 1: Angiotensin II Levels in Plasma During Amlodipine Treatment Period   [ Time Frame: Day 98 ]

12.  Primary:   Part 1: Renin Concentrations From Plasma During Aliskiren Treatment Period   [ Time Frame: Day 42 ]

13.  Primary:   Part 1: Renin Concentrations From Plasma During Amlodipine Treatment Period   [ Time Frame: Day 98 ]

14.  Primary:   Part 1: Renin Activity From Plasma During Aliskiren Treatment Period   [ Time Frame: Day 42 ]

15.  Primary:   Part 1: Renin Activity From Plasma During Amlodipine Treatment Period   [ Time Frame: Day 98 ]

16.  Primary:   Part 2: Change From Baseline in Angiotensin II Levels in Interstitial Fluid of Fat and Skeletal Muscle (Microdialysis) During Double Blind Treatment Period   [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ]

17.  Primary:   Part 2: Change From Baseline in Plasma Angiotensin II Levels During Double Blind Treatment Period   [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ]

18.  Primary:   Part 2: Plasma Renin Activity (PRA) Concentration During Double Blind Treatment Period   [ Time Frame: Day 98 ]

19.  Primary:   Part 2: Plasma Renin Concentration (PRC) Levels During Double Blind Treatment Period   [ Time Frame: Day 98 ]

20.  Secondary:   Part 2: Microdialysis Metabolic Analytes in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)   [ Time Frame: Day 14 and Day 98 ]

21.  Secondary:   Part 2: Change From Baseline in Official Blood Pressure   [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ]

22.  Secondary:   Part 2: Renin Activity and Concentration of Aliskiren and Amlodipine in Fat and Skeletal Muscle Interstitial Fluid   [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ]

23.  Secondary:   Part 2: Change From Baseline in Peripheral Insulin Sensitivity in Response to Insulin Modified Frequently Sampled Intravenous Glucose Test [IM-FSIGT]for Each Tissue (Adipose or Skeletal Muscle)   [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ]

24.  Secondary:   Part 2: Change From Baseline in Mitochondrial Mass in Subcutaneous Fat and Skeletal Muscle (Tissue Biopsies)   [ Time Frame: Placebo Baseline (Day 14), Active Treatment (Day 98) ]

25.  Secondary:   Part 2: Number of Participants With Reported Any Adverse Events, Serious Adverse Events and Death   [ Time Frame: 98 days ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided


Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00498433     History of Changes
Other Study ID Numbers: CSPP100A2238
Study First Received: July 8, 2007
Results First Received: March 21, 2013
Last Updated: October 23, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices