Single Ascending Doses of ZP4207 Administered in HV and in T1D to Evaluate Safety, Tolerability PKs and PDs of ZP4207 Compared to a Comparator
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
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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-
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Neuss、德国、41460
- Profil GmbH
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- 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).
- Male subjects which are healthy for part 1; for part 2 male subjects with T1D
- Age between 18 and 50 years, both inclusive.
- Body weight between 70 and 90 kg, both inclusive.
- Subjects must be in good health according to age (medical history, physical examination, vital signs, ECG, lab assessments), as judged by the investigator
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:
- Male subjects with T1D for at least one year, as defined by the American Diabetes Association.
- Having been treated with insulin for T1D for at least 1 year.
- Stable disease with HbA1c < 8.5 %.
- Stable insulin treatment during participation in trial and 3 month prior to the screening visit.
Exclusion Criteria:
- Known or suspected allergy to trial product(s) or related products.
- Previous participation (randomization) in this trial.
- Receipt of any investigational drug within 3 months prior to screening.
- 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.
- Clinically significant illness within 4 weeks before screening, as judged by the investigator
- Carrier of Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies.
- Positive result of test for HIV antibodies.
- Any clinically significant abnormal hematology,biochemistry or urinalysis screening tests, as judged by the Investigator.
- Clinically significant abnormal ECG at screening as evaluated by Investigator.
- Donation of blood or plasma in the past month, or in excess of 500 ml within 12 weeks prior to screening.
- 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).
- 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.
- 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.
- Surgery or trauma with significant blood loss within the last 2 months prior to screening.
Any condition interfering with trial participation or evaluation or that may be hazardous to the subject.
For part 2, in addition
- Severe hypoglycemic events within one year prior to screening, as judged by the investigator.
- Significant changes in basal insulin within 3 weeks before screening, as judged by the investigator.
- 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
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 |
|---|---|
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实验性的:ZP4207
single dose of ZP4207 in ascending doses (s.c. and i.m.)
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有源比较器:native glucagon
single fixed dose of glucagon
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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
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28 days
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Safety and Tolerability: Changes or findings from baseline in clinical safety laboratory assessments
大体时间:28 days
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28 days
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Safety and Tolerability: Changes or findings from baseline in physical examination
大体时间:28 days
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28 days
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Safety and Tolerability: Changes or findings from baseline in vital signs
大体时间:28 days
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28 days
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Safety and Tolerability: Changes or findings from baseline in ECG
大体时间:28 days
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28 days
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Safety and Tolerability: Findings in local tolerability
大体时间:28 days
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28 days
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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
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5 hours
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Pharmacokinetics: maximum observed concentration of ZP4207 (Cmax)
大体时间:5 hours
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5 hours
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Pharmacokinetics: time to maximum observed concentration of ZP4207 (tmax)
大体时间:5 hours
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5 hours
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Pharmacokinetics: terminal elimination rate constant estimated during the terminal phase of ZP4207 (λz)
大体时间:5 hours
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5 hours
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Pharmacokinetics: the terminal plasma elimination half-life of ZP4207 (t½),
大体时间:5 hours
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5 hours
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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
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5 hours
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Pharmacokinetics: apparent plasma clearance rate of ZP4207(CL) estimated during the terminal Phase (f)
大体时间:5 hours
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5 hours
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Pharmacokinetics: mean residence time for plasma ZP4207 (MRT)
大体时间:5 hours
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5 hours
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Pharmacodynamics (PD): Area under the Plasma glucose curve from time-point 0 until 300 min (AUCgluc 0-300)
大体时间:5 hours
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5 hours
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Pharmacodynamics: maximum observed concentration (Cmax)
大体时间:5 hours
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5 hours
|
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Pharmacodynamics: time to maximum observed concentration (tmax)TPG≥70mg/dL
大体时间:5 hours
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5 hours
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Pharmacodynamics: Time to plasma glucose equal or above (70 mg/dL)
大体时间:5 hours
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5 hours
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合作者和调查者
调查人员
- 首席研究员:Thomas Jax, MD/PhD、Profil GmbH
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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