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

NCT00660309 | Completed Phase 4 Results

• 1 other identifier: CSPP100A2329
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 diabetes mellitus; renal disease; hypertension; renal blood flow; retinal blood flow; aliskiren; irbesartan; captopril

Outcome Measures

Primary Outcomes (4)

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

  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.

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

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

  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.

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

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

  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.

  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.

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

  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.

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

Secondary Outcomes (13)

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

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

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

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

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

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

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

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

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

  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.

Study Arms (2)

Aliskiren

EXPERIMENTAL

On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.

Drug: Aliskiren; Drug: Captopril

Irbesartan

ACTIVE COMPARATOR

On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.

Drug: Irbesartan; Drug: Captopril

Interventions

Aliskiren DRUG

Aliskiren 300 mg tablets

Also known as: SPP100

Aliskiren

Irbesartan DRUG

Irbesartan 300 mg tablets

Irbesartan

Captopril DRUG

Captopril 25 mg tablet

Aliskiren; Irbesartan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis Investigator Site

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Hollenberg NK, Fisher ND, Nussberger J, Moukarbel GV, Barkoudah E, Danser AH. Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients? J Hypertens. 2011 Dec;29(12):2454-61. doi: 10.1097/HJH.0b013e32834c627a.

  PMID: 22002336 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Kidney Diseases; Hypertension

Interventions

aliskiren; Irbesartan; Captopril

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Novartis investigator site

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2008
• First Posted: April 17, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 29, 2012
• Results First Posted: August 29, 2012

Record last verified: 2012-08

Locations

US (1)