The Dose Response of Niacin ER/Lovastatin on Peak Walking Time (PWT) in Patients With Intermittent Claudication - TROPIC

The Dose Response of Niacin ER/Lovastatin on Peak Walking Time (PWT) in Patients With Intermittent Claudication - a Matrix Design

The purpose of this study is to compare the dose response and safety of Niacin ER/Lovastatin, Niaspan® and Lovastatin with each other, in subjects with leg pain caused by a narrowing of their leg arteries.

At least 870 subjects, with leg pain caused by a narrowing of their leg arteries will take part in this study.

Both Niaspan and lovastatin (Mevacor®) are approved by the United States Food and Drug Administration (FDA) to treat high cholesterol. Niacin ER/Lovastatin (Advicor®), a combination of these two drugs, is also approved by the FDA to treat high cholesterol. The use of Niacin ER/Lovastatin to treat narrowing of leg arteries and relieve "intermittent claudication" (leg pain caused by narrowing of the arteries in the leg) is considered investigational. An investigational use is one that is not approved by the FDA.

Study Overview

• Status: Completed
• Conditions: Intermittent Claudication; Peripheral Vascular Disease
• Intervention / Treatment: Drug: Niacin Extended Release and Lovastatin Tablets

Detailed Description

This is a Phase 3, 32-week, double-blind, diet-intervention, randomized, parallel group, ten-arm, multi-center, multi-national, dose titration study evaluating the safety and efficacy of NL in patients with intermittent claudication (IC).

The objectives of this study are to evaluate the safety and efficacy of NL in patients with IC. The primary efficacy analysis will be the percent change from baseline in Peak Walking Time (PWT) calculated from the natural logarithm of the ratio of the time walked on treadmill at the Week 32 Visit divided by the time walked at baseline. Other efficacy measures will include Claudication Onset Time (COT) percent changes from baseline to Week 32 , changes in Ankle Brachial Index (ABI), Quality of Life (QoL) percent changes at Weeks 20 and 32, lower limb amputations, composite of cardiovascular events (MI, stroke, and vascular death), and coronary and peripheral artery revascularizations. Safety variables will include serum transaminases, routine chemistry parameters, hematology, and adverse events. Pharmacokinetic analyses will be conducted as well.

• Study Type: Interventional
• Enrollment: 870
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Tatum Ridge Internal Medicine
    • Scottsdale, Arizona, United States, 85251
      • Scottsdale Cardiovascular Research Institute, LLC
  • California
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
    • Sacramento, California, United States, 95825
      • Sacramento Heart & Vascular Medical Associates
    • Sacramento, California, United States, 95819
      • University of California-Davis; Department of Surgery
    • San Diego, California, United States, 92103
      • Clinical Research Center of California
    • Vista, California, United States, 92083
      • North County Internal Medicine
  • Colorado
    • Denver, Colorado, United States, 80200
      • University of Colorado Health Sciences Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
  • Florida
    • Sarasota, Florida, United States, 34239
      • Cardiovascular Center of Sarasota
  • Georgia
    • Warner Robins, Georgia, United States, 31093
      • Clinical Research Center of Georgia
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • River Cities Cardiology, MPC
  • Maryland
    • Columbia, Maryland, United States, 21044
      • HPV Heart P.A.
  • Michigan
    • Pontiac, Michigan, United States, 48341
      • St. Joseph Mercy-Oakland Research Office
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • North Carolina
    • Statesville, North Carolina, United States, 28625
      • Carolina Pharmaceutical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • COR Clinical Research
  • Oregon
    • Portland, Oregon, United States, 97219
      • New Hope Research of Oregon
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine
    • Philadelphia, Pennsylvania, United States, 19115
      • Radiant Research
    • Wynnewood, Pennsylvania, United States, 19096
      • Mainline Health Heart Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Clinical Cardiology Research Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78205
      • Pro Research Group, LLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Hampton Roads Center for Clinical Research, Inc.
  • Wisconsin
    • Wausau, Wisconsin, United States, 54401
      • Care Foundation, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

• Men & women at least 40 years of age or older. Women must not be pregnant nor breast-feeding & not planning to become pregnant or to breast-feed.
• History of IC of the lower extremities which has been present for at least 6 months with no change in symptoms in the previous 3 months prior to screening.
• LDL-C of <160 mg/dL and Triglycerides <800.

EXCLUSION CRITERIA:

• Severe neuropathy.
• Gross obesity (BMI ≥ 40).
• Presence of critical limb ischemia defined as ischemic rest pain, gangrene, ulceration, or pending amputation of a lower extremity due to severe PAD.
• Surgical intervention to alleviate symptoms of claudication within 6 months or endovascular interventions within 3 months.
• Documented CAD taking any cholesterol-modifying agent and unable to undergo washout as judged by the Investigator or due to personal choice.
• Systolic blood pressure ≥160 mmHg &/or diastolic blood pressure ≥95 mmHg.
• Presence of clinically significant laboratory test abnormalities for liver or renal function tests, thyroid function or HgbA1C.
• History of alcohol abuse or currently drinks alcohol in excess.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Collaborators and Investigators

• Sponsor: Kos Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2003

Study Registration Dates

• First Submitted: October 16, 2003
• First Submitted That Met QC Criteria: October 17, 2003
• First Posted (Estimate): October 20, 2003

Study Record Updates

• Last Update Posted (Estimate): November 2, 2006
• Last Update Submitted That Met QC Criteria: October 31, 2006
• Last Verified: October 1, 2006

More Information

Terms related to this study

• Keywords: PAD; Atherosclerosis; Niacin; Peripheral Arterial Disease; Intermittent Claudication; IC; Lovastatin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Vitamins; Vitamin B Complex; Niacin; Lovastatin; L 647318; Dihydromevinolin
• Other Study ID Numbers: MA-03-010401; The TROPIC Study