Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (GetGoal-M-Asia)
18 de agosto de 2016 atualizado por: Sanofi
Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (With or Without Sulfonylurea): a Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With 24-week Treatment Period
The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010) in comparison to placebo, as an add-on treatment to metformin with or without sulfonylurea, over a period of 24 weeks of treatment.
The primary objective is to assess the effects on glycemic control of lixisenatide (AVE0010) in comparison to placebo as an add-on treatment to metformin with or without sulfonylurea in terms of glycosylated hemoglobin (HbA1c) reduction (absolute change) at Week 24.
The secondary objectives are to assess the effects of lixisenatide over 24 weeks on percentage of patients reaching HbA1c less than (< ) 7 percent (%) or HbA1c less than or equal to (<=) 6.5%, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and glucose excursion during standardized meal test, body weight; to evaluate safety, tolerability, pharmacokinetic (PK) and anti-lixisenatide antibody development.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
The study duration for each patient is 27 weeks +/- 10 days (up to 2 weeks screening + 1 week run-in + 24 weeks double-blind treatment + 3 days follow-up).
Tipo de estudo
Intervencional
Inscrição (Real)
391
Estágio
- Fase 3
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
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Beijing, China, 100034
- Investigational Site Number 156011
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Beijing, China, 100101
- Investigational Site Number 156012
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Beijing, China, 100191
- Investigational Site Number 156019
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Beijing, China, 100700
- Investigational Site Number 156002
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Beijing, China, 100730
- Investigational Site Number 156003
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Beijing, China, 100730
- Investigational Site Number 156009
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Beijing, China, 100853
- Investigational Site Number 156001
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Changchun, China, 130041
- Investigational Site Number 156036
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Changsha, China, 410008
- Investigational Site Number 156016
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Changsha, China, 410011
- Investigational Site Number 156015
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Chengdu, China, 610041
- Investigational Site Number 156006
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Chengdu, China, 610072
- Investigational Site Number 156032
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Dalian, China, 116027
- Investigational Site Number 156010
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Guangzhou, China, 510080
- Investigational Site Number 156004
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Guangzhou, China, 510080
- Investigational Site Number 156008
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Guangzhou, China, 510630
- Investigational Site Number 156025
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Haikou, China, 57028
- Investigational Site Number 156031
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Harbin, China, 150001
- Investigational Site Number 156014
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Hefei, China, 230022
- Investigational Site Number 156029
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Qingdao, China, 266003
- Investigational Site Number 156013
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Shanghai, China, 200003
- Investigational Site Number 156007
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Shanghai, China, 200065
- Investigational Site Number 156030
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Shenyang, China, 110004
- Investigational Site Number 156020
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Suzhou, China, 215004
- Investigational Site Number 156035
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Taiyuan, China, 030001
- Investigational Site Number 156033
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Tianjin, China, 300052
- Investigational Site Number 156037
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Xi'An, China, 710032
- Investigational Site Number 156022
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Xi'An, China, 710061
- Investigational Site Number 156023
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Hong Kong, Hong Kong
- Investigational Site Number 344001
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Hong Kong, Hong Kong
- Investigational Site Number 344003
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Shatin, Nt, Hong Kong
- Investigational Site Number 344002
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Kelantan, Malásia, 16150
- Investigational Site Number 458001
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Kuala Lumpur, Malásia, 59100
- Investigational Site Number 458003
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Putrajaya, Malásia, 62250
- Investigational Site Number 458002
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Bangkok, Tailândia, 10400
- Investigational Site Number 764002
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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 e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion criteria:
- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with metformin alone or metformin with sulfonylurea at the time of the screening visit
Exclusion criteria:
- HbA1c <7% or greater than (>) 10% at screening
- At the time of screening age < legal age of majority
- Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method
- Type 1 diabetes mellitus
- Treatment with metformin not at a stable dose of at least 1.0 gram per day or more than 1.5 gram per day for at least 3 months prior to screening visit
- In case of treatment with sulfonylurea, if the sulfonylurea dosage is less than the maximum effective dose (that is, half of the maximum recommended dose according to local labeling), or is not at a stable (unchanged) dose for at least 3 months prior to screening
- FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter [mmol/L])
- History of hypoglycemia unawareness
- Body mass index <=20 kilogram per square meter (kg/m^2)
- Weight change of >5 kg during the 3 months preceding the screening visit
- History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, or inflammatory bowel disease or patients considered by the investigator at high risk for acute pancreatitis (for example, with known history of biliary gallstone[s], or with very high triglyceride level [>=5.65 mmol/L]) at the time of screening
- Personal or family history of medullary thyroid cancer or genetic conditions that predispose to medullary thyroid cancer (for example, multiple endocrine neoplasia syndromes);
- History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
- Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
- Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
- Known history of drug or alcohol abuse within 6 months prior to the time of screening
- Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period
- Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure (SBP) or diastolic blood pressure (DBP) >180 millimeter of mercury (mmHg) or >95 mmHg, respectively
- Laboratory findings at the time of screening: amylase and/or lipase: >3 times upper limit of normal (ULN); hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3) and/or platelets <100 000/mm^3; calcitonin >20 picogram per milliliter (5.9 picomole per liter) ; and positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
- Any clinically significant abnormality identified on physical examination, laboratory tests, electrocardiogram, or vital signs at the time of screening that, in the judgment of the investigator or any sub-investigator, precludes safe completion of the study or constrains efficacy assessment
- Patients who are considered by the investigator or any sub-investigator as inappropriate for this study for any reason (for example, impossibility to meet specific protocol requirements, such as attending scheduled visits, being able to do self-injections; likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol)
- Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin and sulfonylurea (for example, alpha-glucosidase inhibitor, thiazolidinedione, glucagon-like peptide -1 [GLP-1], receptor agonist, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months prior to the time of screening
- Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to the time of screening
- Use of any investigational drug within 3 months prior to screening;
- Participation in a previous study with lixisenatide
- Renal impairment defined with creatinine >1.4 mg/dL in women and creatinine >1.5 mg/dL in men
- Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
- Allergic reaction to any GLP-1 agonist in the past (for example, exenatide, liraglutide) or to metacresol
- Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in phase (>2 injections missed); and patient with any adverse event which precludes the inclusion in the study, as assessed by the investigator
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 Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Lixisenatide
1-step initiation regimen of lixisenatide: 10 microgram (mcg) once daily (QD) for 2 weeks, followed by 20 mcg QD up to Week 24.
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Auto-administrado por injeções subcutâneas uma vez ao dia na hora anterior ao café da manhã.
Outros nomes:
Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.
Sulfonylurea if given at screening, to be continued up to Week 24.
In patients with a screening HbA1c <8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values.
In patients with a screening HbA1c >=8%, the dose is not to be changed at randomization.
In any case, after Week 12, sulfonylurea is to be continued at a stable dose.
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Comparador de Placebo: Placebo
1-step initiation regimen of volume matching placebo: 10 mcg QD for 2 weeks, followed by 20 mcg QD up to Week 24.
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Outros nomes:
Metformin to be continued at stable dose (at least 1.0 gram per day and not more than 1.5 gram per day) up to Week 24.
Sulfonylurea if given at screening, to be continued up to Week 24.
In patients with a screening HbA1c <8% the dose is decreased by 25% to 50% at randomization and then increased up to the screening dose between Week 4 and 12 as per fasting self-monitored plasma glucose (SMPG) values.
In patients with a screening HbA1c >=8%, the dose is not to be changed at randomization.
In any case, after Week 12, sulfonylurea is to be continued at a stable dose.
Auto-administrado por injeções subcutâneas uma vez ao dia na hora anterior ao café da manhã.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Prazo: Baseline, Week 24
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Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Prazo: Baseline, Week 24
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Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24
Prazo: Baseline, Week 24
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The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal.
Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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Baseline, Week 24
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Change From Baseline in Body Weight at Week 24
Prazo: Baseline, Week 24
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Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24
Prazo: Week 24
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The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Week 24
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Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24
Prazo: Week 24
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The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Week 24
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Change From Baseline in Glucose Excursion at Week 24
Prazo: Baseline, Week 24
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Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration.
Change was calculated by subtracting Baseline value from Week 24 value.
The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
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Baseline, Week 24
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Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period
Prazo: Baseline up to Week 24
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Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication.
If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed.
Threshold values - from baseline to Week 8: fasting SMPG/FPG >250 milligram/deciliter (mg/dL) (13.9 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >220 mg/dL (12.2 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline up to Week 24
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
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Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24
Prazo: Baseline, Week 24
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The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required.
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Baseline, Week 24
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Número de pacientes com hipoglicemia sintomática e hipoglicemia sintomática grave
Prazo: Primeira dose do medicamento do estudo até 3 dias após a administração da última dose
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Hipoglicemia sintomática foi um evento com sintomas clínicos que foram considerados como resultado de um episódio de hipoglicemia com glicose plasmática concomitante inferior a 60 mg/dL (3,3 mmol/L) ou associada à recuperação imediata após administração oral de carboidratos, glicose intravenosa ou glucagon, se nenhuma medida de glicose plasmática estiver disponível.
Hipoglicemia sintomática grave foi um evento de hipoglicemia sintomática no qual o paciente necessitou da ajuda de outra pessoa e foi associado a um nível de glicose plasmática abaixo de 36 mg/dL (2,0 mmol/L) ou recuperação imediata após administração oral de carboidratos, glicose intravenosa ou glucagon , se nenhuma medida de glicose plasmática estiver disponível.
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Primeira dose do medicamento do estudo até 3 dias após a administração da última dose
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, Lv X, Tian H, Jin Kui Y, Su B, Shang S, Niemoeller E. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev. 2014 Nov;30(8):726-35. doi: 10.1002/dmrr.2541.
- Seino H, Onishi Y, Naito Y, Komatsu M. Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. Diabetol Metab Syndr. 2016 Jun 1;8:36. doi: 10.1186/s13098-016-0151-7. eCollection 2016.
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
1 de julho de 2010
Conclusão Primária (Real)
1 de dezembro de 2011
Conclusão do estudo (Real)
1 de dezembro de 2011
Datas de inscrição no estudo
Enviado pela primeira vez
23 de julho de 2010
Enviado pela primeira vez que atendeu aos critérios de CQ
23 de julho de 2010
Primeira postagem (Estimativa)
26 de julho de 2010
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
13 de outubro de 2016
Última atualização enviada que atendeu aos critérios de controle de qualidade
18 de agosto de 2016
Última verificação
1 de agosto de 2016
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- EFC11321
- U1111-1116-8938 (Outro identificador: UTN)
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
produto fabricado e exportado 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 .