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Safety and Pharmacokinetic Study of Y242 in Adult Subjects (Y242-01)

19 janvier 2021 mis à jour par: Imperial College London

A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Y242 in Adult Subjects

Obesity causes 600 premature deaths per week in the UK and existing treatments are not effective. When humans eat, the bowels naturally secrete chemicals into the bloodstream which make people feel full and which stop eating. One of these chemicals is known as Peptide YY (PYY). The investigators have previously shown that injections of PYY reduce appetite and food intake in human volunteers. The investigators have now developed a very similar chemical, Y242, as a treatment for obesity. Y242 has been tested in animals and has been shown to be safe, to reduce their appetite, and to last for much longer than PYY itself. This study will test Y242 to ensure that it is well tolerated in humans, and to see how long it lasts in the blood stream after being injected under the skin. It will also look for any effects on appetite.

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

Obesity causes 600 premature deaths per week in the UK and existing treatments are less than ideal. Intravenous infusion of a hormone called PYY reduces food intake but its effects only last for a few hours and it can cause nausea. Y242 is a longacting analogue of PYY. Given subcutaneously in rodents, it has a profile of action of at least 72 hours and strongly inhibits food intake. It causes weight loss without behavioural effects. With MRC funding, Y242 has passed Good Laboratory Practice toxicology testing and the present proposal is a first in human study to investigate its safety, tolerability and pharmacokinetics in overweight but otherwise healthy men.

The study is a combined single ascending dose (part A) and multiple ascending dose (part B) Phase 1 investigation. The primary objective is to investigate safety and tolerability. The secondary objective is to assess Y242's pharmacokinetic (PK) profile. Possible effects on food consumption will be explored. For part A up to 48 subjects are planned, with up to 40 subjects for part B. In each part subjects are divided into groups, each of which is dosed with the same level, starting with a single dose (part A) much lower than is expected to cause an effect. Subjects are admitted to a Unit so they can be closely observed for adverse effects and safety tests, blood concentrations of the drug and food and liquid intake and output will be monitored. Subjects are allocated at random (like tossing a coin) to receive Y242 or placebo (dummy). Safety, tolerability and pharmacokinetic data will be summarised and available results considered in deciding dose escalation, with stopping rules designed to enable us to explore the relationship between dose and adverse effect (eg nausea) without causing unacceptable nausea or other symptoms in the volunteers.

Type d'étude

Interventionnel

Inscription (Réel)

68

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

      • London, Royaume-Uni, HA1 3UJ
        • Parexel Early Phase Clinical Unit

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:

  • Adult males aged 18 to 50 years inclusive with BMI between 23.0 and 30.0 kg/m^2 inclusive;
  • Subjects who are healthy as determined by pre study medical history, physical examination and 12 lead ECG;
  • Subjects whose clinical laboratory test results are either within the normal range or if outside this range the abnormalities are judged to be not clinically relevant and are acceptable to the Investigator;
  • Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) I and II tests at screening;
  • Subjects who are negative for drugs of abuse and alcohol tests at screening and admissions;
  • Subjects who are non-smokers for at least 3 months preceding screening;
  • Subjects who agree to use medically acceptable methods of contraception for at least 3 months after study drug administration;
  • Subjects who are able and willing to give written informed consent.

Exclusion Criteria:

  • Subjects who do not conform to the above inclusion criteria;
  • Subjects who have a clinically relevant history or presence of gastrointestinal (especially associated with vomiting), respiratory, renal, hepatic, haematological, lymphatic, neurological (especially if associated with balance disorders or vomiting e.g. migraine or labyrinthitis), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders;
  • Subjects who have a clinically relevant surgical history;
  • Subjects who have a clinically relevant family history;
  • Subjects who have a history of relevant atopy;
  • Subjects who have a history of relevant drug hypersensitivity;
  • Subjects who have a history of alcoholism;
  • Subjects who have a history of drug abuse;
  • Subjects who have a history of migraine;
  • Subjects who consume more than 21 units of alcohol a week (unit = 1 glass of wine (125 mL) = 1 measure of spirits = ½ pint of beer);
  • Subjects who have a significant infection or known inflammatory process on screening;
  • Subjects who have acute gastrointestinal symptoms at the time of screening or admission (e.g. nausea, vomiting, diarrhoea, heartburn);
  • Subjects who have an acute infection such as influenza at the time of screening or admission;
  • Subjects who have used prescription drugs within 4 weeks of first dosing;
  • Subjects who have used over the counter medication excluding routine vitamins and paracetamol but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 7 days of first dosing, unless agreed as not clinically relevant by the Principal Investigator and Sponsor;
  • Subjects who have donated blood or blood products within 3 months of Day -2 (admission);
  • Subjects who have used any investigational drug in any clinical trial within 3 months of Day -2 (admission);
  • Subjects who have received the last dose of investigational drug greater than 3 months ago but who are on extended follow-up;
  • Subjects who have previously received Y242;
  • Subjects who are vegans or have any dietary restrictions;
  • Subjects who cannot communicate reliably with the Investigator;
  • Subjects who are unlikely to co-operate with the requirements of the study;
  • History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires at screening.

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 séquentielle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 2mg Y242 (Part A)
Y242 single dose, subcutaneous
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Expérimental: 7.5mg Y242 (Part A)
Y242 single dose, subcutaneous
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Expérimental: 15mg Y242 (Part A)
Y242 single dose, subcutaneous
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Expérimental: 30mg Y242 (Part A)
Y242 single dose, subcutaneous
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Expérimental: 60mg Y242 (Part A)
Y242 single dose, subcutaneous
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Expérimental: 90mg Y242 (Part A)
Y242 single dose, subcutaneous
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Comparateur placebo: Placebo - Part A
0.9% saline
Identical volume to that of Y242
Expérimental: 60mg Y242 (Part B1)
Y242 single subcutaneous dose, administered once a week for 5 weeks
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Expérimental: 90mg Y242 (Part B2-B4)
Y242 single subcutaneous dose, administered once a week for 5 weeks
Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B)
Comparateur placebo: Placebo - Part B
0.9% saline
Identical volume to that of Y242

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
Délai: Up to 73 days
A treatment-emergent AE (TEAE) as defined as an AE that started after administration of IMP; in Part B this was an AE that started after the first dose of IMP. Adverse events with onset prior to dosing were considered as pre-treatment AEs.
Up to 73 days

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Body Weight
Délai: up to 32 day
Summary of Time-Matched % Change from Baseline in Body Weight (Baseline = Day -1) following multiple dose of Y242 (Part B)
up to 32 day

Collaborateurs et enquêteurs

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

Collaborateurs

Les enquêteurs

  • Chaise d'étude: Stephen Bloom DSc, MD FRCP, Imperial College London
  • Chercheur principal: John Lambert, MBBS PhD, Parexel
  • Directeur d'études: Tricia Tan BSc MRCP, MB ChB, Imperial College London

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 (Réel)

1 avril 2012

Achèvement primaire (Réel)

1 février 2013

Achèvement de l'étude (Réel)

1 février 2013

Dates d'inscription aux études

Première soumission

22 décembre 2011

Première soumission répondant aux critères de contrôle qualité

18 janvier 2012

Première publication (Estimation)

24 janvier 2012

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

8 février 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

19 janvier 2021

Dernière vérification

1 janvier 2021

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • QLON/2011/Y242-01
  • 2011-003549-17 (Numéro EudraCT)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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