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Completed

NCT Number: NCT00660309

A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus

The study objective was to assess the effect of single and multiple doses of aliskiren on renal plasma flow, glomerular filtration rate and to compare the effects of single and multiple doses of aliskiren versus captopril or irbesartan on renal blood flow, glomerular filtration rate, and retinal blood flow in patients with type 2 diabetes mellitus.

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Key information

Conditions

Type 2 Diabetes Mellitus Cardiovascular Diseases Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Hypertension Kidney Diseases Male Urogenital Diseases Metabolic Diseases Nutritional and Metabolic Diseases Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Novartis Investigator Site

Boston, Massachusetts, 02115, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Hypertensive, male and females of non-child bearing potential patients, with type 2 diabetes mellitus (T2DM) (diagnosed at least 8 weeks before Screening), with or without renal impairment; estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m^2, documented at least 3 months before the study start, aged 18-75 years with a minimum body weight of 50 kg and having an appropriate intravenous access as determined by the study staff, able to communicate well were enrolled in the study.
  • Patients must be on a stable dose of hypoglycemic medications for at least 8 weeks prior to the study.
  • Patients must be medically able to discontinue anti- hypertensive medications for the duration of the study.

Exclusion criteria

  • Patients with type 1 diabetes mellitus or uncontrolled T2DM (HbA1C> 11%), eGFR <40 mL/min/1.73 m^2 (calculated by the Modification of Diet in Renal Disease (MDRD) formula), renal disease not caused by diabetes or hypertension, serum potassium < 3.5 or > 5.1 mEq/L, heart failure (New York Heart Association (NYHA) Class II-IV) or history of acute/decompensated heart failure within the 6 months prior to dosing, history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to the baseline visit, history of malignancy including leukemia and lymphoma within past five years, hypertensive encephalopathy any time in the past or cerebrovascular accident within the 6 months prior to the baseline visit, or with history of drug or alcohol abuse within the 12 months prior to dosing were excluded from the study.
  • Patients with glaucoma, or prior ocular surgery.
  • Patients with renal disease not caused by diabetes or hypertension.
  • Patients with history of clinically significant drug or atopic allergy, acute or chronic respiratory disease, history of malignancy, or history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any coronary intervention (percutaneous coronary intervention; PCI) during the 6 months prior to the study.
  • Patients who had used any prescription drugs which may affect the renin-angiotensin-aldosterone system or with known effect on renal hemodynamics within 2 weeks prior to dosing and during the study, over-the-counter (OTC) medication within two (2) weeks prior to dosing,
  • Any surgical or medical condition which may jeopardize the patient in case of participation in the study.
  • Participation in any clinical investigation within 4 weeks prior to the study.
  • Donation or loss of 400 mL or more of blood within 8 weeks prior to the study.

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

Aliskiren

Drug

Aliskiren 300 mg tablets

Other names: SPP100

Irbesartan

Drug

Irbesartan 300 mg tablets

captopril

Drug

Captopril 25 mg tablet

Primary outcomes

  1. Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan

    Time frame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.

    Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods.

    The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.

  2. Change From Baseline to Steady State Trough in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan

    Time frame: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .

    Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods.

    This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values.

  3. Change From Baseline to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan

    Time frame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.

    Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods.

    This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.

  4. Change From Single Dose Peak to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan

    Time frame: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.

    Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak. Peak RPF was obtained using a moving average concept.

Secondary outcomes

  1. Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril

    Time frame: Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.

    Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods.

    The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.

  2. Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril

    Time frame: Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.

    Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods.

    The measure of the single dose effect (SDE) for captopril was calculated as Day 1 peak - Day 1 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept.

  3. Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan

    Time frame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.

    Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods.

    The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept.

  4. Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan

    Time frame: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .

    Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods.

    This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values.

  5. Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan

    Time frame: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.

    Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods.

    This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline GFR. Baseline GFR was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak GFR was obtained using a moving average concept.

  6. Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan

    Time frame: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.

    Glomerular filtration rate (GFR) was measured by the clearance of inulin by autoanalyzer methods.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak GFR. Peak GFR was obtained using a moving average concept.

  7. Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan

    Time frame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.

    The following plasma renin concentration effects were assessed:

    The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline.

    SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline.

    Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline.

    Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour.

  8. Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan

    Time frame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.

    The following plasma pro-renin concentration effects were assessed:

    The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline.

    SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline.

    Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline.

    Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour.

  9. Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan

    Time frame: Predose and 5 hours post dose on Days 1, 2 and 15.

    PRA was measured by the trapping method and the following effects assessed:

    The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 baseline.

    SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 baseline.

    Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 baseline / Day 2 baseline.

    Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 baseline.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour.

  10. Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan

    Time frame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.

    The following angiotensin I effects were assessed:

    The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline.

    SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline.

    Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline.

    Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour.

  11. Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan

    Time frame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.

    The following angiotensin II effects were assessed:

    The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline.

    SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline.

    Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline.

    Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour.

  12. Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan

    Time frame: Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.

    The following serum aldosterone effects were assessed:

    The single dose effect (SDE) for captopril, expressed as the ratio to pre-dose measurement on Day 1, = Day 1, 5 hour / Day 1 Baseline.

    SDE for aliskiren and irbesartan = Day 2, 5 hour / Day 2 Baseline.

    Steady state trough effect (multiple dose effect at steady state; MDE_SS) = Day 15 Baseline / Day 2 Baseline.

    Steady State peak effect (maximum multiple dose effect; MDE_Max) = Day 15, 5 hour / Day 2 Baseline.

    Accumulation of peak effect from single dose to multiple dose (MDE_Acc) = Day 15, 5 hour / Day 2, 5 hour.

  13. Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan

    Time frame: Baseline (Day 1), Day 2 and Day 15.

    Retinal blood flow was assessed using the laser Doppler technique. The blood flow in the superior temporal retinal artery in one of the eyes of each study participant was determined.

    The Single dose effect of aliskiren or irbesartan was measured as the change/difference between Day 2 and baseline measurements.

    The Multiple dose effect of aliskiren or irbesartan wsas measured as the change/difference between Day 15 and Day 2 measurements

Sponsors and collaborators

Lead sponsor

Novartis

Industry

Registry information

Official study title

An Open-label, Randomized, Parallel-group Study to Evaluate the Acute and Steady-state Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Apr 17, 2008
Registry last updated
Aug 29, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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