Effect of Lapaquistat Acetate Combined With Fenofibrate on Blood Cholesterol Levels
2012年5月23日 更新者：Takeda
A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 or Placebo When Coadministered With Fenofibrate in Subjects With Combined Hyperlipidemia
The purpose of this study is to compare changes in cholesterol levels in patients with elevated blood cholesterol with administration of lapaquistat acetate, once daily (QD), and fenofibrate.
調査の概要
詳細な説明
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. It has been established that lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality. As a result of this finding, the National Cholesterol Education Program Adult Treatment Panel III identifies control of low-density lipoprotein cholesterol as essential in the prevention and management of coronary heart disease.
Currently, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line monotherapies prescribed to reduce low-density lipoprotein cholesterol, after diet and therapeutic lifestyle change. However, low doses of statins often fail to produce the Adult Treatment Panel III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. This in turn may result in decreased tolerability and potential safety concerns.
At higher doses, statins are associated with various myopathies ranging from rare occurrences of rhabdomyolysis and myositis to more frequent symptoms of muscle weakness, cramps, or pain; these can occur with mild or no increases in creatine kinase. Statin use also is associated with increases in liver transaminase levels. These tolerability and safety concerns may contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses.
TAK-475 (lapaquistat acetate) inhibits the cholesterol synthesis pathway at a different step than statins (acting on squalene synthase rather than 3-hydroxy-3-methylglutaryl coenzyme A); it does not reduce concentrations of isoprenylated intermediates believed to be responsible for the myopathies associated with statin use.
This study was conducted to determine whether lapaquistat acetate with fenofibrate has the potential to be more effective than fenofibrate by itself in lowering low-density lipoprotein cholesterol.
研究の種類
介入
入学 (実際)
213
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alabama
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Huntsville、Alabama、アメリカ
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Arizona
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Sierra Vista、Arizona、アメリカ
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California
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Beverly Hills、California、アメリカ
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Long Beach、California、アメリカ
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Spring Valley、California、アメリカ
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Colorado
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Colorado Springs、Colorado、アメリカ
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Golden、Colorado、アメリカ
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Connecticut
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Waterbury、Connecticut、アメリカ
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Florida
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Jacksonville、Florida、アメリカ
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Kissimmee、Florida、アメリカ
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Miami、Florida、アメリカ
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Ocala、Florida、アメリカ
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Pembroke Pines、Florida、アメリカ
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Pinellas Park、Florida、アメリカ
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West Palm Beach、Florida、アメリカ
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Georgia
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Warner Robins、Georgia、アメリカ
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Illinois
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Chicago、Illinois、アメリカ
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Peoria、Illinois、アメリカ
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Indiana
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Indianapolis、Indiana、アメリカ
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Kansas
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Wichita、Kansas、アメリカ
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Minnesota
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Edina、Minnesota、アメリカ
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Missouri
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St. Louis、Missouri、アメリカ
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North Carolina
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Raleigh、North Carolina、アメリカ
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Winston-Salem、North Carolina、アメリカ
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Ohio
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Cincinnati、Ohio、アメリカ
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Columbus、Ohio、アメリカ
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Oregon
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Hillsboro、Oregon、アメリカ
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Pennsylvania
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Beaver、Pennsylvania、アメリカ
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South Carolina
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Goose Creek、South Carolina、アメリカ
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Tennessee
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Nashville、Tennessee、アメリカ
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Virginia
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Norfolk、Virginia、アメリカ
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Richmond、Virginia、アメリカ
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British Columbia
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Coquitlam、British Columbia、カナダ
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Victoria、British Columbia、カナダ
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Ontario
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London、Ontario、カナダ
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Toronto、Ontario、カナダ
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Women of childbearing potential must not be pregnant as determined by a negative serum human chorionic gonadotropin, not lactating, not planning on becoming pregnant between Screening and 30 days following the last dose of study medication, and agreed to use acceptable forms of contraception during the study.
- Prior to Randomization, must have a mean low density lipoprotein cholesterol greater than or equal to 100 mg/dL (2.59 mmol/L) for 2 consecutive samples. The difference between the two individual low density lipoprotein cholesterol values not to exceed 15% of the higher value.
- Prior to Randomization, must have mean triglycerides greater than or equal to 150 and less than or equal to 600 mg/dL (1.70 and 6.78 mmol/L, respectively) for 2 consecutive samples. The upper value for either triglycerides sample must have been less than or equal to 650 mg/dL (7.35 mmol/L).
- Clinical laboratory evaluations (including clinical chemistry [fasted for at least 10 hours], hematology and urinalysis) within the reference range for the testing laboratory unless results deemed not clinically significant or considered within normal limits for this subject by the investigator or the sponsor.
- Willing and able to continue to comply with a standardized low cholesterol diet.
Exclusion Criteria:
- Alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Serum creatinine greater than 1.5 mg/dL (133 μmol/L).
- Creatine phosphokinase greater than 3 times the upper limit of normal.
- Diabetes with a hemoglobin A1c greater than 8 % at Visit 1.
- Previous history of cancer in remission for less than 5 years prior to the first dose of study medication. Does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.
- An endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism. Subjects with hypothyroidism on appropriate replacement therapy (defined as stable thyroid hormone replacement therapy at least 3 months prior to Visit 1 and thyrotropin levels less than 1.5 times the upper limit of normal) are eligible for enrollment. If thyrotropin is greater than 1.5 times upper limit of normal, a free thyroxine level is to be determined. If the free thyroxine is within normal limits for that subject, the subject may continue in the study.
- History of myocardial infarction, unstable angina, transient ischemic attacks, cerebrovascular accident, percutaneous coronary intervention, coronary or peripheral arterial surgery (bypass graft surgery) in the 6 months prior to Visit 1.
- Positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report.
- Positive human immunodeficiency virus status or is taking anti-retroviral medications, as determined by medical history and/or subject's verbal report.
- Unable or unwilling to discontinue excluded medications or to continue stable doses of "stable dose" medications or required treatment with any excluded medication during the study.
- Exposure to TAK-475 in other studies or currently is participating in another investigational study or has participated in an investigational study within the past 30 days or, for drugs with a long half-life, within a period of less than 5 times the drug's halflife.
- Known hypersensitivity or history of adverse reaction to any fibrate.
- History or presence of clinically significant food allergy that would prevent adherence to the therapeutic lifestyle change (or equivalent) diet.
- Known homozygous familial hypercholesterolemia or known Type III hyperlipoproteinemia (familial dysbetalipoproteinemia).
- Active cholecystitis or known cholelithiasis (a fibrate risk factor).
- Severe renal or hepatic dysfunction, including biliary cirrhosis during Run-In or at Randomization (a fibrate risk factor).
- Fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain.
- Uncontrolled hypertension (defined as resting diastolic blood pressure greater than100 mm Hg or resting systolic blood pressure greater than 160 mm Hg) at Visit 1.
- Inflammatory bowel disease or any other malabsorption syndrome or has had gastric bypass or any other surgical procedure for weight loss.
- Unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
- Unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent was available.
- History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within the past 2 years.
- Any other serious disease or condition at Screening or at Randomization that might reduce life expectancy, impair successful management according to the protocol, or make the subject an unsuitable candidate to receive study medication.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Lapaquistat Acetate 100 mg QD + Fenofibrate 145 mg QD
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Lapaquistat acetate 100 mg, tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
他の名前：
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アクティブコンパレータ：Fenofibrate 145 mg QD
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Lapaquistat acetate placebo-matching tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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Percent change from Baseline in direct fasting plasma low-density lipoprotein cholesterol.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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二次結果の測定
結果測定 |
時間枠 |
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Change from baseline in calculated low-density lipoprotein cholesterol.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in non- high-density lipoprotein cholesterol.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in total cholesterol.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in apolipoprotein B.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in triglycerides.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in high-density lipoprotein cholesterol.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in apolipoprotein A1.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in very-low-density lipoprotein cholesterol.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in derived ratios including total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, and apolipoprotein B/ apolipoprotein Al.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Change from baseline in high-sensitivity C-reactive protein.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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Percentage of Subjects Achieving Target Direct low-density lipoprotein cholesterol Levels.
時間枠：Week 12 or Final Visit.
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Week 12 or Final Visit.
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Senior Medical Director、Takeda
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2006年2月1日
一次修了 (実際)
2007年1月1日
研究の完了 (実際)
2007年1月1日
試験登録日
最初に提出
2008年12月19日
QC基準を満たした最初の提出物
2008年12月19日
最初の投稿 (見積もり)
2008年12月23日
学習記録の更新
投稿された最後の更新 (見積もり)
2012年5月24日
QC基準を満たした最後の更新が送信されました
2012年5月23日
最終確認日
2012年5月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。