医療ニュースを色々見ていたら、Parkinson病治療薬である MAO-B阻害薬 rasagilineの臨床試験の結果がニュースになっていました。日本国内で使用出来る MAO-B阻害薬としては selegirineがありますが、rasagilineは海外でしか販売されていません。面白かったのが臨床試験の名前。なんと、ANDANTE (Add oN to Dopamine AgoNists in the TrEatment of Parkinson’s disease) というらしいのです。音楽好きとして、食いついたのはその一点。アンダンテは「歩く速さで」という意味の音楽記号です。

これまで、L-Dopaに上乗せして rasagilineの有効性を評価した臨床試験はあったようなのですが、ドパミンアゴニストへの上乗せは初めての試験だったようです。試験内容をごく簡単に説明すると、ドパミンアゴニスト単剤での治療で効果不十分の早期パーキンソン病患者に、rasagiline ないしはプラセボを上乗せしました。18週間後、rasagiline投与群では、プラセボ群に対して有意に UPDRS (Unified Parkinson’s Disease Rating Scale) Parts I~IIIの改善を認めました。プラセボと比べて有害事象の有意な差はありませんでした。

New Data Show Azilect^® (rasagiline tablets) Provided Clinical Benefit in Patients with Early Parkinson’s When Added to Sub-Optimally Controlled Patients on Dopamine Agonist Therapy

Results Add to Evidence for Azilect as an Effective and Well-Tolerated Treatment Option at Different Stages of the Progression of Parkinson’s Disease (PD)

JERUSALEM–(BUSINESS WIRE)–Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) and H. Lundbeck A/S announced today that a double-blind, placebo controlled, randomized, multicenter study of Azilect^® (rasagiline tablets) met its primary endpoint. The study, known as ANDANTE (Add oN to Dopamine AgoNists in the TrEatment of Parkinson’s disease), assessed the efficacy and tolerability of Azilect as add-on treatment to dopamine agonists compared to placebo. While the efficacy of Azilect as adjunct to levodopa has been established in previous studies (leading to its indication as adjunct therapy to levodopa), its efficacy in combination with dopamine agonist monotherapy has not previously been studied.

Results from the study demonstrated that the addition of Azilect 1mg/day provided a statistically significant improvement (Primary endpoint: treatment effect ± SE -2.4 ± 0.95 [95% CI -4.3,-0.5, p=0.012]) in total Unified Parkinson’s Disease Rating Scale (UPDRS) score (Parts I, II and III, version three) from baseline to week 18 in patients sub-optimally controlled with dopamine agonist monotherapy compared to placebo. Azilect was well-tolerated with no significant difference in adverse events compared to placebo.

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STUDY DETAILS

ANDANTE was an 18-week, double-blind, placebo controlled, randomized, multi-center study assessing the safety and clinical benefit of rasagiline compared to placebo as add-on therapy to stable dose of dopamine agonists (DAs) in the treatment of early PD.

In addition to the above stated primary endpoint results, data from the secondary endpoint analysis showed the addition of Azilect^® resulted in a statistically significant improvement in the UPDRS motor examination subscale (Part III) (p=0.007). There were no significant differences between groups for the UPDRS activities of daily living (ADL) (p=0.301) or CGI-I scores. Azilect was well-tolerated in the study.

ANDANTE was conducted at 50 research sites in the United States. A total of 328 patients on sub-optimal DA monotherapy randomized into the study to add-on treatment with Azilect (N=163) or placebo (N=165). Volunteers returned to the clinic at nine weeks for an interim visit and again at 18 weeks, for an end of study visit.

To be enrolled patients needed to be on a stable DA monotherapy for ≥ 30 days. Patients included could not receive an optimal therapeutic dose of DAs due to intolerable side effects or were no longer experiencing sufficient control of their PD symptoms and required an additional therapeutic agent. Rescue treatment with levodopa was allowed once the patient had started treatment with study drug and had completed four weeks of treatment. DA therapy could not be adjusted during the study.

The side effect profile of Azilect as add-on to DA therapy was evaluated for changes in nature and frequency of dopaminergic adverse events.

ABOUT AZILECT^® (UNITED STATES)

AZILECT^® (rasagiline tablets) is indicated for the treatment of the signs and symptoms of Parkinson’s disease (PD) both as initial therapy alone and to be added to levodopa later in the disease.

Patients should not take AZILECT^® if they are taking meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, cyclobenzaprine, or other monoamine oxidase inhibitors (MAOIs), as it could result in a serious reaction. Patients should inform their physician if they are taking, or planning to take, any prescription or over-the-counter drugs, especially antidepressants and ciprofloxacin. Patients with moderate to severe liver disease should not take AZILECT^®. Patients should not exceed a dose of 1 mg per day of AZILECT^® in order to prevent a possibly dangerous increase in blood pressure.

Side effects seen with AZILECT^® alone are flu syndrome, joint pain, depression, and indigestion; and when taken with levodopa are uncontrolled movements (dyskinesia), accidental injury, weight loss, low blood pressure when standing, vomiting, anorexia, joint pain, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, and fall.

See additional important information at http://www.azilect.com/Resources/PDFs/PrescribingInformation-pdf.aspx. For hardcopy releases, please see enclosed full prescribing information.

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rasagilineは使ったことのない薬剤 (日本では保険適応外) なので特にコメントはありませんが、自分が臨床試験を組むことがあるとしたら、このように略語が音楽用語になるようにしてみたいものだと思いました。

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