24-hour UFC ≤2.0 x ULN and below or equal to their baseline values continued blinded treatment at the randomized dose until Month 6. Patients who did not meet these criteria were unblinded and the dose was increased by 0.3mg b.i.d. After the initial 6 months in the study, patients entered an additional 6-month open-label treatment period. The dosage could be reduced by 0.3mg b.i.d. at any time during the study for intolerability. The primary efficacy endpoint was the proportion of patients who achieved normalization of mean 24-hour UFC levels after 6 months of therapy and did not dose increase during this period.
At Month 6, the percentages of responders for the primary endpoint were 15% and 26% in the 0.6mg b.i.d. and 0.9mg b.i.d. groups, respectively. The percentages of patients with mUFC ≤ ULN or ≥ 50% reduction from baseline, a less stringent endpoint than the primary endpoint, were 34% in the 0.6mg bid and 41% in the 0.9mg bid groups. Dose increases appeared to have minimal effect on 24-hour UFC response. The mean and median percentage changes in UFC from baseline were -22% and -47% in the 0.6mg b.i.d. group, and -42% and -46% in the 0.9mg b.i.d. group.
Legal Classification:
Rx
Adults:
Initially 0.6mg or 0.9mg by SC inj twice daily; usual range: 0.3mg–0.9mg twice daily. Titrate based on response and tolerability. Hepatic impairment: moderate (Child-Pugh B): initially 0.3mg twice daily; max 0.6mg twice daily; severe (Child-Pugh C): avoid.
Children:
<18years: not established.
Warnings/Precautions:
Monitor for hypocortisolism; consider temporary dose reduction, interruption or steroid replacement therapy if occurs. Diabetes: risk of hyperglycemia; initiate or adjust anti-diabetic treatment if occurs. Congenital long QT prolongation. Cardiac disease (including recent MI, CHF, unstable angina, significant bradycardia). High-grade heart block. Hypokalemia. Hypomagnesemia. Correct and monitor electrolytes prior to starting and during therapy. Hepatic impairment. Monitor baseline fasting plasma glucose, HbA1c, LFTs, ECG, gallbladder ultrasound, pituitary function prior to initiation and periodically during treatment. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interaction(s)
Caution with anti-arrhythmics or other drugs that may prolong the QT interval. May antagonize cyclosporine (adjust dose). May potentiate bromocriptine; dose reduction may be needed.
Adverse Reaction(s)
Diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, diabetes; bradycardia, QT prolongation.
How Supplied:
Single-dose ampule—60
LAST UPDATED:
4/9/2013
FDA批准新孤儿药Signifor(帕瑞泰)治疗库欣病
12月14日，美国食品与药物管理局(FDA)批准了新“孤儿药”Signifor (帕瑞肽, pasireotide diaspartate)注射液用于治疗不能通过手术治疗的库欣病(Cushing’s disease)患者。
库欣病是肾上腺制造的皮质醇激素过度生成引起。在垂体腺的肿瘤导致肾上腺过度刺激，它导致皮质醇过度生成. 皮质醇调节机体内许多重要功能，包括对应急和损伤的反应。有库欣氏病患者可能有体重，葡萄糖不能耐受或糖尿病，高血压，容易挫伤增加，和增加对感染风险。
FDA药品评估和研究中心内分泌代谢药物部门主任 Mary Parks博士表示，尽管手术切除肿瘤已日趋成为库欣病的一线治疗手段，但Signifor (帕瑞肽)对于无法手术或手术治疗失败的库欣病患者是一种新的治疗选择。
Signifor (帕瑞肽)为一种生长激素抑制剂类似物,可通过与其受体结合抑制ACTH的释放从而减少皮质醇分泌。Signifor (帕瑞肽)的安全性和有效性是通过一项前瞻性、随机、双盲的Ⅲ期临床试验进行评估的,纳入162名尿游离皮质醇(UFC)水平为正常上限值的1.5倍且无法进行手术治疗的库欣病患者，患者随机接受Signifor 900μg或600μg皮下注射,6个月后，900μg治疗组患者UFC水平达到主要终点。结果显示，试验中接受Signifor (帕瑞肽)治疗的患者24小时尿量中皮质醇水平降低
