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Single Ascending Doses of ZP4207 Administered in HV and in T1D to Evaluate Safety, Tolerability PKs and PDs of ZP4207 Compared to a Comparator

2016年1月21日 更新者:Zealand Pharma

A Randomized, Double-blinded Trial of Single Ascending Doses of ZP4207 Administered s.c. or i.m. to HV and a SD of ZP4207 Administered s.c. to Hypoglycemic T1D to Evaluate the Safety, Tolerability, PKs and PDs of ZP4207 as Compared to an Active Comparator

The trial is a randomized, double-blind First in Human trial to evaluate the safety and tolerability of ZP4207 in healthy volunteers (HV) and in insulin-induced hypoglycemic T1D (type 1 diabetes) subjects as compared to native glucagon. The trial includes two parts.

Part 1 includes dose escalation of ZP4207 in cohorts of 8 subjects. In each cohort, subjects will be randomized 3:1 to receive either a single ascending dose of ZP4207 (6 subjects) or a single fixed dose (SD) of native glucagon (2 subjects). The doses will be administered s.c. in 4-5 cohorts and i.m. in 3 cohorts.

Part 2 includes two sequence groups of 10 hypoglycemic T1D subjects. The subjects will be treated with fixed single doses of ZP4207 and native glucagon s.c. in a sequential cross-over design in a randomized treatment order.

研究概览

地位

完全的

条件

研究类型

介入性

注册 (实际的)

111

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Neuss、德国、41460
        • Profil GmbH

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 50年 (成人)

接受健康志愿者

是的

有资格学习的性别

男性

描述

Inclusion Criteria:

  1. Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject).
  2. Male subjects which are healthy for part 1; for part 2 male subjects with T1D
  3. Age between 18 and 50 years, both inclusive.
  4. Body weight between 70 and 90 kg, both inclusive.
  5. Subjects must be in good health according to age (medical history, physical examination, vital signs, ECG, lab assessments), as judged by the investigator
  6. A subject who is surgically sterilized or must be willing to refrain from sexual intercourse during the trial and until one month after completion of the trial or if sexually active, using condom and partner practices contraception during the trial and until one month after completion of the trial.

    For part 2, in addition:

  7. Male subjects with T1D for at least one year, as defined by the American Diabetes Association.
  8. Having been treated with insulin for T1D for at least 1 year.
  9. Stable disease with HbA1c < 8.5 %.
  10. Stable insulin treatment during participation in trial and 3 month prior to the screening visit.

Exclusion Criteria:

  1. Known or suspected allergy to trial product(s) or related products.
  2. Previous participation (randomization) in this trial.
  3. Receipt of any investigational drug within 3 months prior to screening.
  4. A history or presence of cancer, diabetes (part 1 only), or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, hematological, dermatological, venereal, neurological, psychiatric diseases or other major diseases.
  5. Clinically significant illness within 4 weeks before screening, as judged by the investigator
  6. Carrier of Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies.
  7. Positive result of test for HIV antibodies.
  8. Any clinically significant abnormal hematology,biochemistry or urinalysis screening tests, as judged by the Investigator.
  9. Clinically significant abnormal ECG at screening as evaluated by Investigator.
  10. Donation of blood or plasma in the past month, or in excess of 500 ml within 12 weeks prior to screening.
  11. A significant history of alcoholism or drug/chemical abuse, or who has a positive result in the urine drug screen, or who consumes more than 28 units of alcohol per week (one unit of alcohol equals about 250 ml of beer, 1 glass of wine, or 20 ml of spirits).
  12. Habitual smoking, i.e., daily smoking or more than 7 cigarettes/week within the last 3 months prior to screening. Subjects have to accept refraining from smoking while at the clinical site.
  13. Subjects with mental incapacity or language barriers which preclude adequate understanding or cooperation, who are unwilling to participate in the trial, or who in the opinion of the Investigator should not participate in the trial.
  14. Surgery or trauma with significant blood loss within the last 2 months prior to screening.
  15. Any condition interfering with trial participation or evaluation or that may be hazardous to the subject.

    For part 2, in addition

  16. Severe hypoglycemic events within one year prior to screening, as judged by the investigator.
  17. Significant changes in basal insulin within 3 weeks before screening, as judged by the investigator.
  18. Clinically relevant diabetic complications (macrovascular disease with symptoms of coronary artery disease or peripheral vascular disease, microvascular disease with symptoms of neuropathy, gastroparesis, retinopathy, nephropathy, or poor blood glucose control with polyuria, polydipsia, or weight loss), as judged by the investigator.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:双倍的

武器和干预

参与者组/臂
干预/治疗
实验性的:ZP4207
single dose of ZP4207 in ascending doses (s.c. and i.m.)
有源比较器:native glucagon
single fixed dose of glucagon

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Safety and Tolerability: Number of participants with adverse events
大体时间:28 days
28 days
Safety and Tolerability: Changes or findings from baseline in clinical safety laboratory assessments
大体时间:28 days
28 days
Safety and Tolerability: Changes or findings from baseline in physical examination
大体时间:28 days
28 days
Safety and Tolerability: Changes or findings from baseline in vital signs
大体时间:28 days
28 days
Safety and Tolerability: Changes or findings from baseline in ECG
大体时间:28 days
28 days
Safety and Tolerability: Findings in local tolerability
大体时间:28 days
28 days

次要结果测量

结果测量
大体时间
Pharmacokinetics (PK): Area under the curve (AUC) from time-point 0 until 300min
大体时间:5 hours
5 hours
Pharmacokinetics: maximum observed concentration of ZP4207 (Cmax)
大体时间:5 hours
5 hours
Pharmacokinetics: time to maximum observed concentration of ZP4207 (tmax)
大体时间:5 hours
5 hours
Pharmacokinetics: terminal elimination rate constant estimated during the terminal phase of ZP4207 (λz)
大体时间:5 hours
5 hours
Pharmacokinetics: the terminal plasma elimination half-life of ZP4207 (t½),
大体时间:5 hours
5 hours
Pharmacokinetics: apparent volume of distribution of ZP4207 based on plasma concentration values (Vz), estimated during the terminal Phase (f): (Vz/f)
大体时间:5 hours
5 hours
Pharmacokinetics: apparent plasma clearance rate of ZP4207(CL) estimated during the terminal Phase (f)
大体时间:5 hours
5 hours
Pharmacokinetics: mean residence time for plasma ZP4207 (MRT)
大体时间:5 hours
5 hours
Pharmacodynamics (PD): Area under the Plasma glucose curve from time-point 0 until 300 min (AUCgluc 0-300)
大体时间:5 hours
5 hours
Pharmacodynamics: maximum observed concentration (Cmax)
大体时间:5 hours
5 hours
Pharmacodynamics: time to maximum observed concentration (tmax)TPG≥70mg/dL
大体时间:5 hours
5 hours
Pharmacodynamics: Time to plasma glucose equal or above (70 mg/dL)
大体时间:5 hours
5 hours

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Thomas Jax, MD/PhD、Profil GmbH

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2014年12月1日

初级完成 (实际的)

2015年4月1日

研究完成 (实际的)

2015年4月1日

研究注册日期

首次提交

2015年2月3日

首先提交符合 QC 标准的

2015年2月19日

首次发布 (估计)

2015年2月20日

研究记录更新

最后更新发布 (估计)

2016年1月22日

上次提交的符合 QC 标准的更新

2016年1月21日

最后验证

2016年1月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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