INV-144 Versus Losartan in Hypertension and Type 2 Diabetes Mellitus Patients With Macroalbuminuria

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
InVasc Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01398423
First received: July 19, 2011
Last updated: August 5, 2012
Last verified: August 2012
  Purpose

A randomized, double-blind, active control trial to determine the safety, efficacy and pharmacokinetics of INV-144 versus losartan potassium plus placebo in subjects with hypertension and Type 2 diabetes mellitus with nephropathy as evidenced by albuminuria.


Condition Intervention Phase
Hypertension
Diabetes Mellitus, Type 2
Drug: Active Control
Drug: INV-144
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12 Week, Phase II Trial of the Safety, Pharmacokinetics, and Efficacy of INV-144 Compared With Losartan Potassium in Patients With Hypertension and Type 2 Diabetes Mellitus With Nephropathy

Resource links provided by NLM:


Further study details as provided by InVasc Therapeutics, Inc.:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Safety will be monitored throughout the study by evaluation of adverse events (AEs), physical examinations (PEs), clinical laboratory results, vital signs, and electrocardiograms (ECGs).


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Efficacy will be evaluated by measurement of UACR, systolic and diastolic blood pressure, and the HOMA-IR ratio.


Enrollment: 88
Study Start Date: June 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active control
Losartan potassium (50 mg) plus placebo to match alpha lipoic acid (600 mg)
Drug: Active Control
Losartan potassium (50 mg) plus placebo to match alpha lipoic acid (600 mg)
Experimental: INV-144
INV-144 is a combination drug product consisting of losartan potassium (50mg) and alpha lipoic acid (600 mg)
Drug: INV-144
INV-144 is a combination drug product consisting of losartan potassium (50mg) and alpha lipoic acid (600 mg)

Detailed Description:

A multicenter, randomized, double-blind, parallel-group, active-control trial is designed to evaluate the safety and efficacy of INV-144 versus losartan plus placebo co-administered once daily for 12 weeks in subjects who have type 2 diabetes and hypertension with nephropathy as evidenced by albuminuria.

Approximately 92 adult subjects will be enrolled and randomized in a 1:1 ratio to receive either INV-144 or losartan plus placebo once daily for 12 weeks. The goal is to have approximately 80 subjects complete the entire study.

The trial will consist of a 4-week open-label losartan run-in period, a 12-week double-blind active treatment period, and a 4-week safety follow-up period. Efficacy will be evaluated by measurement of UACR, systolic and diastolic blood pressure, and the HOMA-IR ratio. Safety will be monitored throughout the study by evaluation of adverse events (AEs), physical examinations (PEs), clinical laboratory results, vital signs, and electrocardiograms (ECGs).

Blood samples for PK analysis will be obtained in a subset of approximately 22 subjects, at 2 to 4 sites, to ensure that PK data are obtained from a minimum of 9 subjects in each treatment arm.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women, 18 to 85 years of age, inclusive.
  2. Able and willing to understand and provide written informed consent.
  3. Documented hypertension defined by 1 of the following:

    Currently treated with antihypertensive medications, or Untreated with a seated systolic blood pressure (mean of 3 readings) between 126 and 180 millimeters of mercury (mm Hg).

  4. Documented type 2 diabetes mellitus defined by 1 of the following:

    Currently treated with anti-diabetic medication (oral and/or insulin), or Fasting serum glucose level ≥126 mg/dL.

  5. Documented nephropathy evidenced by a UACR of 300 to 3000 mg/g.
  6. Both men and women of child bearing potential (i.e., not surgically sterile or post-menopausal defined as age >40 years without menses for ≥2 years) must agree to use 1 of the following forms of reliable contraception:

Abstinence, meaning a total lack of sexual activity, Oral contraceptives ("the pill") or other hormonal contraceptive methods, Intrauterine device, Double-barrier method (diaphragm or condom plus spermicidal cream), or If female, male partner sterilization.

Exclusion Criteria:

  1. Required use of an ACE inhibitor, ARB, direct renin inhibitor, or aldosterone antagonist other than study drug, while on the study.
  2. Systolic blood pressure >180 mm Hg (mean of 3 seated readings, 5 minutes apart, using the subject's dominant arm).
  3. Chronic kidney disease stage 4 or higher defined as an estimated glomerular filtration rate <30 mL/min per 1.73 m2 (abbreviated MDRD equation).
  4. Hepatic impairment defined by serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST)>2 x the upper limit of normal.
  5. Diagnosis of type 1 diabetes or non-diabetic renal disease, including but not limited to renal-artery stenosis, primary glomerular disease, autoimmune renal diseases, etc.
  6. Severe anemia defined as hemoglobin < 8 g/dL.
  7. Congestive heart failure with New York Heart Association Class II, III, or IV symptoms.
  8. Thiamine (Vitamin B1) deficiency or known alcohol abuse within the past year. If alcohol abuse is suspected, subject must have a normal thiamine blood level documented prior to study entry.
  9. Any radiocontrast-facilitated study within 30 days prior to Study Day 1.
  10. Cerebrovascular accident within the previous 6 months, or have had a transient ischemic attack within the previous year.
  11. Pregnant or nursing women; women of childbearing potential must have a negative serum pregnancy test at Screen.
  12. Known adverse reaction to losartan and/or ALA.
  13. Participation in another clinical trial or have received an investigational agent for any reason within 30 days of Study Day 1.
  14. Any other condition that in the opinion of the Investigator, may adversely affect the safety of the subject, the subject's ability to complete the study, or the outcome of the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01398423

Locations
United States, California
Garden Grove, California, United States, 92844
La Mesa, California, United States, 91942
Northridge, California, United States, 91324
Riverside, California, United States, 92505
Tustin, California, United States, 92780
United States, Florida
Kissimmee, Florida, United States, 34741
Miami, Florida, United States, 33015
United States, Georgia
Macon, Georgia, United States, 31217
Tucker, Georgia, United States, 30084
United States, Maryland
Reisterstown, Maryland, United States, 21136
United States, Minnesota
Brooklyn Center, Minnesota, United States, 55430
United States, North Carolina
Cary, North Carolina, United States, 27511
Greenville, North Carolina, United States, 27834
New Bern, North Carolina, United States, 28562
Raleigh, North Carolina, United States, 27610
United States, South Carolina
Aiken, South Carolina, United States, 29801
United States, Texas
San Antonio, Texas, United States, 78215
San Antonio, Texas, United States, 78228
United States, Virginia
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
InVasc Therapeutics, Inc.
Investigators
Study Director: William Schaeffer InVasc Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: InVasc Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01398423     History of Changes
Other Study ID Numbers: INV144-201
Study First Received: July 19, 2011
Last Updated: August 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by InVasc Therapeutics, Inc.:
Hypertension
Diabetes mellitis
Nephropathy
Albuminuria

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Thioctic Acid
Losartan
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on April 17, 2014