- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT02744820
Multiple Ascending Dose Study of GMC-252-L-Lys Salt in Healthy Subjects and Type 2 Diabetics
A Double Blind, Placebo-controlled, Randomised, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GMC-252 in Healthy Male Subjects and Male Type 2 Diabetics
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of multiple oral doses of GMC-252-L-Lysine salt (GMC-252) in healthy subjects and type 2 diabetics.
The secondary objective is to explore the effect of multiple oral doses of GMC-252 on pharmacodynamic(PD) parameters in type 2 diabetics.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
-
-
-
Belfast, Reino Unido, BT2 7BA
- BioKinetic Europe Ltd.
-
Merthyr Tydfil, Reino Unido, CF48 4DR
- Simbec Research Ltd
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria
Part 1 (Healthy Subjects) and Part 2 (Type 2 Diabetic Patients):
- Diet: Able to eat standard food, no vegetarians.
- Compliance: Understands and is willing, able and likely to comply with all study procedures and restrictions.
- Consent: Demonstrates understanding of the study and has given signed, voluntary written informed consent.
- Have no known hypersensitivity to diflunisal, NAC or other NSAIDs.
- No history of blood diseases including but not limited to clinically significant platelet diseases and coagulation abnormalities.
- No clinically relevant gastrointestinal disease.
- Have an estimated creatinine (CREA) clearance>70 mL/min/surface area (CREA clearance will be calculated from the serum CREA value by using the Cockroft and Gault formula).
- Have no history of heart failure or uncontrolled hypertension or other known clinically significant cardiovascular disease.
- Have no history of bronchial asthma or 'Aspirin Triad' (chronic rhino-sinusitis with polyps, severe asthma and intolerance to aspirin or other NSAIDs).
- Have no clinically significant abnormality of liver tests before entry into the study.
- A negative urinary drugs of abuse screen, determined within 28 days before the first dose (N.B. a positive alcohol result may be repeated at the discretion of the Investigator).
- Negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
- No clinically significant abnormalities in a 12-lead ECG determined within 28 days before the first dose.
- No history of clinically significant renal disease or any food intolerance.
- Willing to use 2 effective methods of contraception i.e. established method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from Day 1 until 3 months afterwards.
Additional Criteria for Part 1 (Healthy Subjects):
- Healthy males aged 18 to 55 inclusive.
- Body mass index (BMI) within the range of 18-30 kg/m2 inclusive.
- Non-Smokers (including e-cigarettes) who have abstained from smoking for at least 6 months.
Additional Criteria for Part 2 (Type 2 Diabetic Patients):
- Males aged 18 to 65 inclusive. BMI within the range of 18-38 kg/m2 inclusive.
- Diagnosis of T2DM according to the World Health Organization criteria.
- HbA1c between 7.0% and 12.0 % inclusive.
- Currently treated with metformin with a stable treatment regimen for 3 months or more prior to the Screening Visit, and not receiving other anti-diabetic medications. Allowed medication during the study include metformin, statin (3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors), paracetamol up to 3 g/day, low doses of aspirin and antihypertensive drugs if the doses are not changed in the 3 months before the start of screening. Other allowed medications will be approved by PI and Sponsor before a patient can be enrolled. Diflunisal (a test drug component) may decrease the antihypertensive activityof many of the currently used antihypertensive medications, such as β-blockers, alpha (α)-blockers, loop diuretics, angiotensin converting enzyme (ACE inhibitors), angiotensin 2 receptor blockers, calcium channel blockers. Therefore, patients who are on current stable antihypertensive medications will be subjected to close monitoring of their blood pressure throughout the study.
- Stable dietary habits and regimen of treatment for concomitant diseases for 1 month or more prior to the Screening Visit.
- Subject able and willing to undergo oral glucose tolerance test (OGTT).
Exclusion Criteria
Part 1 (Healthy Subjects) and Part 2 (Type 2 Diabetic Patients):
- A clinically significant history of previous allergy / sensitivity to any of the GMC-252 components, NAC or diflunisal.
- Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
- Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months. (N.B. washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
- Donation of 450 mL or more blood within the previous 3 months.
- A clinically significant history of drug, alcohol or other substance abuse in the past 2 years.
Additional Criteria for Part 1 (Healthy Subjects):
- A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
- Receipt of regular medication within 28days of the first dose that may have an impact on the safety and objectives of the study (at the Investigator's discretion).
- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
Additional Criteria for Part 2 (Type 2 Diabetic Patients):
Diagnosis/General Health:
- Diabetic autonomic or sensory neuropathy including gastroparesis, diabetic nephropathy or untreated active proliferative retinopathy.
- Clinically significant abnormalities in laboratory evaluation (including clinical biochemistry, haematology and urinalysis) in the opinion of the Investigator.
Diseases:
- Uncontrolled hypertension (blood pressure ≥ 160/100 mmHg), severe or unstable angina, coronary insufficiency, congestive heart failure, clinically significant (in the opinion of the Investigator) renal or hepatic disease.
- Previous gastric or intestinal surgerythat might impact drug absorption.
- Malignancy within 5 years of the start of the study, except for successfully treated local basal cell carcinoma
- Current or relevant previous history, of clinically significant psychiatric illness.
Medications:
- Current use of insulin or any previous use of insulin other than as part of a clinical trial or associated with surgical procedure or acute illness for up to 7 days.
- Use of any anti diabetic medication other than metformin in the 3 months prior to study entry.
- Current use of any anticoagulant drug e.g. warfarin, heparin.
- Prior use (within 48 h of dosing) of any drug that could have altered gastric motility (domperidone, cyclizine, metoclopramide, prochlorperazine), or cholestyramine.
Plano de estudo
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 |
---|---|
Comparador de Placebo: Cohort 1 (Part 1)
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo |
1 dose by oral route, once a day, 28 days
Outros nomes:
Matching doses by oral route, once a day, 28 days
|
Comparador de Placebo: Cohort 2 (Part 1)
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo |
1 dose by oral route, once a day, 28 days
Outros nomes:
Matching doses by oral route, once a day, 28 days
|
Comparador de Placebo: Cohort 3 (Part 1)
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo |
1 dose by oral route, once a day, 28 days
Outros nomes:
Matching doses by oral route, once a day, 28 days
|
Comparador de Placebo: Cohort 4 (Part 2)
Multiple ascending oral administrations of GMC-252-L-Lysine Salt and matching placebo Interventions: Drug: GMC-252-L-Lysine Salt Other: Placebo |
1 dose by oral route, once a day, 28 days
Outros nomes:
Matching doses by oral route, once a day, 28 days
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Number of Participants with Serious and Non-Serious Adverse Events
Prazo: 28 days plus 14 days post last dose
|
Physical status (Vital signs; 12-lead ECG; Urinalysis; Haematology and biochemistry)
|
28 days plus 14 days post last dose
|
Medidas de resultados secundários
Medida de resultado |
Prazo |
---|---|
Maximal Concentration (Cmax)
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
Area Under the Concentration-Time Curve
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
Time to reach steady state
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Preliminary effect on Fasting blood glucose (Cohort 4 only)
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
|
Preliminary effect on oral glucose tolerance test (OGTT) (Cohort 4 only)
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
|
Preliminary effect on Insulin levels (Cohort 4 only)
Prazo: 28 days plus 14 days post last dose
|
Insulin
|
28 days plus 14 days post last dose
|
Preliminary effect on C-Peptide levels (Cohort 4 only)
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
|
Preliminary effect on Fructosamine levels (Cohort 4 only)
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
|
Preliminary effect on %HbA1c (Cohort 4 only)
Prazo: 28 days plus 14 days post last dose
|
28 days plus 14 days post last dose
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- GMC-252-1.03
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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 .
Ensaios clínicos em GMC-252-L-Lysine Salt
-
Genmedica Therapeutics S.L.Simbec ResearchRescindidoSaudávelReino Unido