ORLANDO (EGMN) – An investigational once-weekly form of taspoglutide controlled blood glucose as well as – or better than – more frequent treatments with insulin glargine, exenatide, or sitagliptin.

The results of the three phase III trials – all part of Roche AG’s T-emerge trial series – come on the heels of the Swiss company’s announcement that it will probably delay its approval filing for the drug by at least 1 year. Roche pinned the delay on gastrointestinal side effects and injection site reactions associated with taspoglutide, which were well in evidence in all three studies.

“It’s a minimum delay of 12-18 months,” said Terence Hurley, a spokesman for Genentech, Roche’s U.S. corporate entity. “Roche will continue to study the drug and the hypersensitivity reactions during this period.”

All of the T-emerge studies are 52-week trials. The data reported at the annual meeting of the American Diabetes Association covered 24 weeks; the rest of the data are being analyzed and will be available later this year, Mr. Hurley said in an interview. “That is when we will have a complete picture of taspoglutide’s efficacy and actual safety profile.”

None of the presenters discussed the company’s intent to delay taspoglutide’s debut, but all remarked that it caused significantly greater incidence of nausea and vomiting than did any of the comparator drugs. T-emerge 2, 3 and 4 used taspoglutide in two different doses: 10 mg weekly and 20 mg weekly.

T-emerge 2 compared the two taspoglutide arms to twice-daily exenatide 10 mcg for 24 weeks in 1,149 patients. Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center, reported the outcomes.

The patients’ mean age was 56 years; their mean duration of type 2 diabetes was almost 6 years. At baseline, the mean hemoglobin A_1c was 8%, and the mean body mass index (BMI), 33 kg/m².

At the end of the study, the mean decrease in HbA_1c was about 1%, and not different between the groups. “This shows that taspoglutide is not inferior to exenatide,” Dr. Rosenstock said.

However, significantly more patients taking the study medication hit the target HbA_1c goal of 7% or less (61% taspoglutide 10 mg, 63% taspoglutide 20 mg, 46% exenatide).

Adverse events were significantly more common in the taspoglutide groups, with the most common being nausea and vomiting. Nausea occurred in 40% of those taking 10 mg and 47% of those taking 20 mg of the study drug, compared with 30% of those taking exenatide. Vomiting was also more common in the taspoglutide groups (21% with 10 mg taspoglutide, 24% with 20 mg taspoglutide, vs. 11% with exenatide).

Skin reactions were significantly more common among those taking taspoglutide, with nodules occurring in 8%, compared to 0.5% of the exenatide group. Pruritus occurred in 7% of those taking 10 mg taspoglutide, 9% of those taking 20 mg taspoglutide, and 0.3% of those taking exenatide.

In the T-emerge 3 trial, randomization was to either 10 mg or 20 mg taspoglutide once a week, or daily insulin glargine in 1,049 patients whose type 2 diabetes was inadequately controlled on metformin. These patients were similar to the T-emerge 2 patients in age, BMI, and disease duration. The mean HbA_1c at baseline was 8.3%. Dr. Michael Nauck of the Diabetes Center Bad Lauterberg, in Bad Lauterberg im Harz, Germany, presented the results.

After 24 weeks, the mean decrease in HbA_1c was similar between all three groups (less than 1%). Significantly more patients taking the study drug achieved an HbA_1c of 7% or lower (34% with 10 mg taspoglutide, 41% with 20 mg taspoglutide, and 28% with insulin glargine). The results were similar with a target of 6.5% or lower (18%, 24%, vs. 14%).

Patients taking taspoglutide lost significantly more weight than those taking insulin glargine (3 kg, 4 kg, 0.4 kg). In a subset of 100 patients tested for postprandial glucose levels, those taking taspoglutide fared better, compared with their baseline levels, than did those in the insulin glargine group (–15 mg/dL, –12 mg/dL, and +6 mg/dL).

Nausea (45% vs. 2%) and vomiting (13% vs. 6%), however, were more common in the study drug groups, compared with the insulin glargine group.

Injection site reactions occurred in up to 16% of the study medication groups and none of those taking insulin.

Dr. Richard Bergenstal, executive director of the International Diabetes Center at Park Nicollet in Minneapolis, Minnesota, presented the results of T-emerge 4. This study randomized 666 patients to either of the taspoglutide doses, oral sitagliptin 100 mg daily, or placebo for 24 weeks.

HbA_1c was significantly reduced in those taking the study drug, compared with those taking sitagliptin (1.2% mg/dL vs. 0.8% sitagliptin). Fasting blood glucose was also significantly reduced, compared with sitaglitpin (42 mg/dL for 20 mg taspoglutide vs. 24 mg/dL sitagliptin). Patients taking the study drug lost significantly more weight (up to 2.5 kg vs. 0.5 kg).

Again, gastrointestinal adverse events were significantly more common with the study drug and were the cause of withdrawal from the study in 14% of the 20-mg group, 10% of the 10-mg group, and 0.5% of the sitagliptin group.

All of the T-emerge studies were sponsored by Roche; all of the presenters disclosed being on Roche’s advisory board and receiving research support from the company.

 

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

奥兰多(EGMN)——试验药taspoglutide每周1次在控制血糖水平方面与甘精胰岛素、艾塞那肽或西他列汀等常用降糖药同等有效或更优。

 

这3项III期临床试验均为罗氏公司T-emerge 系列试验的组成部分，在该瑞士公司宣布很可能会将该药的审批文件推迟至少一年后不久得出上述试验结果。罗氏将推迟原因归为与taspoglutide有关的胃肠道不良反应和注射部位反应，这些不良反应在所有这3项研究中均很明显。

 

“最少推迟12~18个月，”罗氏(美国)公司的基因泰克公司发言人Terence Hurley说。“罗氏将继续研究此药及期间的超敏反应。”

 

所有的T-emerge研究均为历时52周的试验。美国糖尿病学会年会上报告的数据涵盖了24周的研究成果；其余数据正在分析之中，今年下半年可得出结果，Hurley 先生在一次受访中说：“届时，我们会对taspoglutide的疗效和实际安全性有一个全面说明。”

 

所有发言者均未谈及公司推迟taspoglutide上市的意图，但均表示，与其他任何同类药相比，服用该药所引起的恶心、呕吐的发生率明显增加。T-emerge 2、3及4使用了2种不同剂量的taspoglutide：10 mg 每周1次和20 mg每周1次。

 

T-emerge 2在1,149例患者中将两个taspoglutide治疗组与艾塞那肽治疗组(10 μg，每天2次，持续24周)进行比较。达拉斯糖尿病与内分泌中心主任Julio Rosenstock博士报告了这些结果。

 

受试者的平均年龄为56岁；2型糖尿病的平均病程约为6年。基线时，平均HbA_1c为8%，平均体重指数(BMI)为33 kg/m²。

 

研究结束时，HbA_1c平均降低约1%，无组间差异。Rosenstock博士说：“这表明，taspoglutide不劣于艾塞那肽。”

 

然而，服用试验药的患者中HbA_1c达到目标水平(≤7%)的病例数明显增加(10 mg taspoglutide治疗组为61%，20 mg taspoglutide 治疗组为63%，而艾塞那肽治疗组为46%)。

 

Taspoglutide 治疗组中不良事件的发生率明显偏高，以恶心、呕吐为最多见。10 mg taspoglutide治疗组恶心发生率为40%， 20 mg试验药治疗组为47%，而艾塞那肽治疗组为30%。呕吐在taspoglutide治疗组中亦较多见(10 mg taspoglutide治疗组为21%，20 mg taspoglutide治疗组为24%，而艾塞那肽治疗组为11%)。

 

在服用Taspoglutide的患者中发生皮肤反应者明显偏多，结节发生率为8%，而艾塞那肽治疗组为0.5%。10 mg taspoglutide治疗组瘙痒发生率为7%，20 mg taspoglutide治疗组为9%，而服用艾塞那肽者为0.3%。

 

T-emerge 3试验以1,049例服用二甲双胍血糖控制不佳的2型糖尿病患者为受试者，将其随机分配至每周1次10 mg或20 mg taspoglutide治疗组，或每天1次甘精胰岛素治疗组。这些受试者在年龄、BMI和病程方面与T-emerge 2试验中的受试者相近。基线时平均HbA_1c水平为8.3%，德国Bad Lauterberg 糖尿病中心的Michael Nauck博士公布了结果。

 

24周后，3组之间HbA_1c的平均降幅相近(不足1%)。服用试验药的患者中HbA_1c≤7%这一目标的达标率显著增加(10 mg taspoglutide治疗组为34%，20 mg taspoglutide治疗组为41%，而甘精胰岛素治疗组为28%)。在≤6.5%这一目标水平达成方面，结果亦与之相近。

 

Taspoglutide治疗组患者的体重减轻幅度显著大于甘精胰岛素治疗组(3 kg、4 kg、0.4 kg)。在100例检测餐后血糖水平的受试者中，与甘精胰岛素治疗组相比，taspoglutide治疗组患者相对于基线水平有更多改善(-15 mg/dl， -12 mg/dl和+6 mg/dl)。

 

但试验药治疗组恶心(45% 对  2%)和呕吐(13% 对6%)较甘精胰岛素治疗组更为多见。

 

试验药治疗组注射部位反应的发生率达16%，而胰岛素治疗组发生例数为0。

 

明尼苏达州明尼阿波利斯Park Nicollet国际糖尿病中心执行董事Richard Bergenstal博士展示了T-emerge 4的研究结果。该研究将666例患者随机分入任一Taspoglutide剂量组、口服西他列汀治疗组(100 mg，每天1次)或安慰剂对照组，历时24周。

 

与西他列汀治疗组相比，试验药治疗组HbA_1c显著降低[1.2% mg/dL 对 0.8% (西他列汀治疗组)]。空腹血糖水平亦较西他列汀治疗组显著降低[42 mg/dl(20 mg Taspoglutide治疗组) 对 24 mg/dl(西他列汀治疗组)]。试验药治疗组患者体重显著减轻(达2.5 kg 对 0.5 kg)。

 

另外，试验药治疗组胃肠道不良事件的发生率显著增加，该不良反应导致20 mg治疗组有14%、10 mg治疗组有10%以及西他列汀治疗组有0.5%的患者退出研究。

 

所有的T-emerge研究均由罗氏资助；所有发言人均披露为罗氏顾问委员会成员，并获得罗氏的研究资助。

 

爱思唯尔 版权所有