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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

21 janvier 2016 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Type d'étude

Interventionnel

Inscription (Réel)

111

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Neuss, Allemagne, 41460
        • Profil GmbH

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 50 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Homme

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: ZP4207
single dose of ZP4207 in ascending doses (s.c. and i.m.)
Comparateur actif: native glucagon
single fixed dose of glucagon

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Safety and Tolerability: Number of participants with adverse events
Délai: 28 days
28 days
Safety and Tolerability: Changes or findings from baseline in clinical safety laboratory assessments
Délai: 28 days
28 days
Safety and Tolerability: Changes or findings from baseline in physical examination
Délai: 28 days
28 days
Safety and Tolerability: Changes or findings from baseline in vital signs
Délai: 28 days
28 days
Safety and Tolerability: Changes or findings from baseline in ECG
Délai: 28 days
28 days
Safety and Tolerability: Findings in local tolerability
Délai: 28 days
28 days

Mesures de résultats secondaires

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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Les enquêteurs

  • Chercheur principal: Thomas Jax, MD/PhD, Profil GmbH

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 décembre 2014

Achèvement primaire (Réel)

1 avril 2015

Achèvement de l'étude (Réel)

1 avril 2015

Dates d'inscription aux études

Première soumission

3 février 2015

Première soumission répondant aux critères de contrôle qualité

19 février 2015

Première publication (Estimation)

20 février 2015

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

22 janvier 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

21 janvier 2016

Dernière vérification

1 janvier 2016

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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