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

19 de janeiro de 2021 atualizado por: 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.

Visão geral do estudo

Status

Concluído

Condições

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Real)

68

Estágio

  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

      • London, Reino Unido, HA1 3UJ
        • PAREXEL Early Phase Clinical Unit

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 50 anos (Adulto)

Aceita Voluntários Saudáveis

Sim

Gêneros Elegíveis para o Estudo

Macho

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição sequencial
  • Mascaramento: Dobro

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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)
Experimental: 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)
Experimental: 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)
Experimental: 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)
Experimental: 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)
Experimental: 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)
Comparador de Placebo: Placebo - Part A
0.9% saline
Identical volume to that of Y242
Experimental: 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)
Experimental: 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)
Comparador de Placebo: Placebo - Part B
0.9% saline
Identical volume to that of Y242

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Body Weight
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Colaboradores

Investigadores

  • Cadeira de estudo: Stephen Bloom DSc, MD FRCP, Imperial College London
  • Investigador principal: John Lambert, MBBS PhD, Parexel
  • Diretor de estudo: Tricia Tan BSc MRCP, MB ChB, Imperial College London

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

1 de abril de 2012

Conclusão Primária (Real)

1 de fevereiro de 2013

Conclusão do estudo (Real)

1 de fevereiro de 2013

Datas de inscrição no estudo

Enviado pela primeira vez

22 de dezembro de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

18 de janeiro de 2012

Primeira postagem (Estimativa)

24 de janeiro de 2012

Atualizações de registro de estudo

Última Atualização Postada (Real)

8 de fevereiro de 2021

Última atualização enviada que atendeu aos critérios de controle de qualidade

19 de janeiro de 2021

Última verificação

1 de janeiro de 2021

Mais Informações

Termos relacionados a este estudo

Outros números de identificação do estudo

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

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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