目的:随机化,双盲,交叉试验,以确认Somapacitan的生物等效性,长效生长激素(GH),5毫克/1.5毫升和10毫克/1.5毫升等摩尔剂量。
方法:健康参与者随机(1:1:1)接受皮下注射somapacitan治疗,一次给药期为5mg/1.5mL,两次给药期为10mg/1.5mL。资格标准包括年龄18-45岁和体重指数18.5-24.9kg/m2。排除标准包括GH缺乏史,以前的GH治疗,体重>100.0kg,并在筛选前45天或先前研究产品半衰期的五倍内参与研究药物的任何临床试验。从时间0到最后一次可量化观察的曲线下面积(AUC0-t),最大血清浓度(Cmax),评估了Somapacitan的Cmax时间和终末半衰期以及安全性.
结果:总计,33名参与者被随机分组。对于AUC0-t,估计治疗比率(ETR)(5mg/1.5mL对10mg/1.5mL)为0.95(90%置信区间[CI]0.89-1.01).点估计和90%CI在可接受范围内(0.80-1.25)。对于Cmax,ETR为0.77(90%CI0.68-0.89)。点估计和90%CI超出可接受范围(0.80-1.25)。每种强度的平均胰岛素样生长因子-I(IGF-I)和IGF-I标准偏差评分浓度-时间曲线几乎相同。没有发现新的安全问题。
结论:AUC0-t符合Somoapacitan5mg/1.5mL和10mg/1.5mL的生物等效性标准,但Cmax不符合。这两种强度具有相等的IGF-I响应。
背景:ClinicalTrials.gov,NCT03905850(2019年4月3日)。
Somapacitan是一种长效生长激素,用于治疗生长激素缺乏的人。Somapacitan用注射笔注射到皮肤下。剂量基于人的体重以及他们对治疗的反应。我们比较了注射笔的两种强度,每1.5毫升含5或10毫克索马帕西坦。对于这两种优势,参与者给予相同剂量.我们想了解身体是否以相同的方式将这些不同的力量吸收到血液中。我们还测量了胰岛素样生长因子-I(IGF-I)的水平,生长激素存在于血液中时形成的一种激素,来观察不同强度的索玛卡坦对身体的影响。在我们的研究中,33名健康成人使用somapacitan5毫克笔进行了一轮注射,使用somapacitan10毫克笔进行了两轮注射,至少相隔3周。我们发现血液中吸收的索马帕西坦的量没有差异,也不知道它吸收的速度有多快。在使用10mg笔的人群中,血液中somapacitan的峰值含量更高。在使用任一注射笔之后,IGF-I水平没有差异。总的来说,我们的结果表明,两种优势的somapacitan导致类似的反应在体内。有不同的强度选项可以让医生更容易地调整SONAPAACTAN的剂量,取决于患者对治疗的反应。
OBJECTIVE: Randomised, double-blind, crossover
trial to confirm bioequivalence of somapacitan, a long-acting growth hormone (GH), in 5 mg/1.5 mL and 10 mg/1.5 mL strengths in equimolar doses.
METHODS: Healthy participants were randomised (1:1:1) to subcutaneous somapacitan treatment in one dosing period with 5 mg/1.5 mL and two periods with 10 mg/1.5 mL. Eligibility criteria included age 18-45 years and body mass index 18.5-24.9 kg/m2. Exclusion criteria included history of GH deficiency, previous GH treatment, weight > 100.0 kg and participation in any clinical
trial of an investigational medicinal product within 45 days or five times the half-life of the previous investigational product before screening. Area under the curve from time 0 until last quantifiable observation (AUC0-t), maximum serum concentration (Cmax), time to Cmax and terminal half-life of somapacitan and safety were assessed.
RESULTS: In total, 33 participants were randomised. For AUC0-t, estimated treatment ratio (ETR) (5 mg/1.5 mL versus 10 mg/1.5 mL) was 0.95 (90% confidence interval [CI] 0.89-1.01). Point estimate and 90% CIs were within the acceptance range (0.80-1.25). For Cmax, ETR was 0.77 (90% CI 0.68-0.89). Point estimate and 90% CIs were outside the acceptance range (0.80-1.25). Mean insulin-like growth factor-I (IGF-I) and IGF-I standard deviation score concentration-time curves for each strength were almost identical. No new safety issues were identified.
CONCLUSIONS: Bioequivalence criterion for somapacitan 5 mg/1.5 mL and 10 mg/1.5 mL was met for AUC0-t but not for Cmax. The two strengths had equivalent IGF-I responses.
BACKGROUND: ClinicalTrials.gov, NCT03905850 (3 April 2019).
Somapacitan is a long-acting growth hormone used to treat people with growth hormone deficiency. Somapacitan is injected under the skin with an injection pen. The dose is based on a person’s body weight and how they respond to treatment. We compared two strengths of injection pen, containing either 5 or 10 mg of somapacitan per 1.5 mL. For both strengths, participants were given the same dose. We wanted to understand whether the body absorbs these different strengths into the bloodstream in the same way. We also measured levels of insulin-like growth factor-I (IGF-I), a hormone formed when growth hormone is present in the blood, to see the effect of different strengths of somapacitan on the body. In our
study, 33 healthy adults received one round of injection using the somapacitan 5 mg pen and two rounds using the somapacitan 10 mg pen, all at least 3 weeks apart. We found no differences in the amount of somapacitan being absorbed into the bloodstream, nor how fast it was absorbed. The peak amount of somapacitan in the bloodstream was higher in people using the 10 mg pen. There were no differences in IGF-I levels following use of either injection pen. Overall, our results show both strengths of somapacitan lead to similar responses in the body. Having different strength options could allow doctors to adjust the dose of somapacitan more easily, depending on a patient’s response to treatment.