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.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
-
Neuss、ドイツ、41460
- Profil GmbH
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的:ZP4207
single dose of ZP4207 in ascending doses (s.c. and i.m.)
|
|
|
アクティブコンパレータ:native glucagon
single fixed dose of glucagon
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
Safety and Tolerability: Number of participants with adverse events
時間枠:28 days
|
28 days
|
|
Safety and Tolerability: Changes or findings from baseline in clinical safety laboratory assessments
時間枠:28 days
|
28 days
|
|
Safety and Tolerability: Changes or findings from baseline in physical examination
時間枠:28 days
|
28 days
|
|
Safety and Tolerability: Changes or findings from baseline in vital signs
時間枠:28 days
|
28 days
|
|
Safety and Tolerability: Changes or findings from baseline in ECG
時間枠:28 days
|
28 days
|
|
Safety and Tolerability: Findings in local tolerability
時間枠:28 days
|
28 days
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Pharmacokinetics (PK): Area under the curve (AUC) from time-point 0 until 300min
時間枠:5 hours
|
5 hours
|
|
Pharmacokinetics: maximum observed concentration of ZP4207 (Cmax)
時間枠:5 hours
|
5 hours
|
|
Pharmacokinetics: time to maximum observed concentration of ZP4207 (tmax)
時間枠:5 hours
|
5 hours
|
|
Pharmacokinetics: terminal elimination rate constant estimated during the terminal phase of ZP4207 (λz)
時間枠:5 hours
|
5 hours
|
|
Pharmacokinetics: the terminal plasma elimination half-life of ZP4207 (t½),
時間枠: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)
時間枠:5 hours
|
5 hours
|
|
Pharmacokinetics: apparent plasma clearance rate of ZP4207(CL) estimated during the terminal Phase (f)
時間枠:5 hours
|
5 hours
|
|
Pharmacokinetics: mean residence time for plasma ZP4207 (MRT)
時間枠:5 hours
|
5 hours
|
|
Pharmacodynamics (PD): Area under the Plasma glucose curve from time-point 0 until 300 min (AUCgluc 0-300)
時間枠:5 hours
|
5 hours
|
|
Pharmacodynamics: maximum observed concentration (Cmax)
時間枠:5 hours
|
5 hours
|
|
Pharmacodynamics: time to maximum observed concentration (tmax)TPG≥70mg/dL
時間枠:5 hours
|
5 hours
|
|
Pharmacodynamics: Time to plasma glucose equal or above (70 mg/dL)
時間枠:5 hours
|
5 hours
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Thomas Jax, MD/PhD、Profil GmbH
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。