Healthy subjects and subjects with Type 2 Diabetes MedDRA version: 14.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Code: EV-077-3201-2TBS
Pharmaceutical Form: Capsule
Current Sponsor code: EV-077-3201-2TBS
Other descriptive name: EV-077-3201-2 tert-butylamine salt (TBS)
Concentration unit: mg milligram(s)
Sponsors
Evolva SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All Parts (A, B and C) 1.Informed consent obtained before any trial-related activities. 2.A male with a partner of childbearing potential must only be allowed to participate if: •he and his partner are willing to use a medically acceptable method of birth control (e.g. condom in combination with hormonal contraception or intrauterine device, or a diaphragm with spermicide) during the study and for 3 months after participation in the study, or •he is vasectomized (> 6 months), or •he has a sterilized partner (> 6 months), or •he is abstinent during the study and for 3 months after participation in the study. Parts A and B only 3.Healthy male subjects aged 18 to 50 inclusive. 4.Body weight 70 to 90 kg inclusive. Part C only 5.Male or female subjects aged 18 to 70 years inclusive. (NB. All females must be of non-reproductive potential, i.e. post-menopausal, post-hysterectomy, bilateral tubal ligation or bilateral oophorectomy). 6.Body mass index (BMI) between 25.0 and 40.0 kg/m2 (both inclusive). 7.Subjects with type 2 diabetes mellitus according to American Diabetes Association (ADA) definition for a duration of at least 3 years, on a stable therapy with oral anti-diabetic drugs (OAD) or with insulin, with or without one or two OADs or a glucagon like peptide-1 (GLP-1) agonist, or glitazones. Stable baseline therapy is defined as unchanged dose regimen for at least 3 months before administration of the study drug. 8.HbA1c = 6.0 and = 9.0 %. 9.History of hyperlipidemia, with either elevated LDL cholesterol (>140 mg/dL) without therapy, or treatment with statins (NB. Patients on statin therapy must have a 2 week wash-out before they can enter the study). 10.History of hypertension, either with systolic blood pressure levels between 140 to 160 mmHg without treatment, or treatment with ACE inhibitors or ARB, which should be stable over the previous 3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 86 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10 ;Inclusion criteria: All Parts (A, B and C) 1.Informed consent obtained before any trial-related activities. 2.A male with a partner of childbearing potential must only be allowed to participate if: •he and his partner are willing to use a medically acceptable method of birth control (e.g. condom in combination with hormonal contraception or intrauterine device, or a diaphragm with spermicide) during the study and for 3 months after participation in the study, or •he is vasectomized (> 6 months), or •he has a sterilized partner (> 6 months), or •he is abstinent during the study and for 3 months after participation in the study. Parts A and B only 3.Healthy male subjects aged 18 to 50 inclusive. 4.Body weight 70 to 90 kg inclusive. Part C only 5.Male or female subjects aged 18 to 70 years inclusive. (NB. All females must be of non-reproductive potential, i.e. post-menopausal, post-hysterectomy, bilateral tubal ligation or bilateral oophorectomy). 6.Body mass index (BMI) between 25.0 and 40.0 kg/m2 (both inclusive). 7.Subjects with type 2 diabetes mellitus according to American Diabetes Association (ADA) definition for a duration of at least 3 years, on a stable therapy with oral anti-diabetic drugs (OAD) or with insulin, with or without one or two OADs or a glucagon like peptide-1 (GLP-1) agonist, or glitazones. Stable baseline therapy is defined as unchanged dose regimen for at least 3 months before administration of the study drug. 8.HbA1c = 6.0 and = 9.0 %. 9.History of hyperlipidemia, with either elevated LDL cholesterol (>140 mg/dL) without therapy, or treatment with statins (NB. Patients on statin therapy must have a 2 week wash-out before they can enter the study). 10.History of hypertension, either with systolic blood pressure levels between 140 to 160 mmHg without treatment, or treatment with ACE inhibitors or ARB, which should be stable over the previous 3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 86 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: All Parts (A, B and C) 1.Employees or personnel affiliated with the Sponsor or Investigator. 2.Previous participation (randomisation) in this trial. 3.The intake of any investigational drug within one month or five half-lives, whatever is longer, before administration of study drug. 4.A history of significant multiple drug allergies or with a known allergy to the trial product or any medicine chemically related to the trial product, as judged by the Investigator. 5.Clinically significant acute illness within 2 weeks before administration of study drug, including severe infections, as judged by the Investigator. 6.Abnormal and clinically significant ECG at screening. 7.Donation of any blood or plasma in the past month or in excess of 500 mL within the 12 weeks preceding screening. 8.Intake of paracetamol within 7 days before start of treatment. 9.Surgery or trauma with significant blood loss within the last 3 months before administration of study drug. 10.Smokers (negative cotinine test required). 11.A positive result of the human immunodeficiency virus (HIV) 1 and 2 test and/or positive Hepatitis B antigen and/or positive Hepatitis C antibody screen. 12.A history of alcoholism or drug/chemical abuse, or a positive result in the urine/ drug/ breath alcohol screen, or consumption of more than 14 units of alcohol per week (one unit of alcohol equals about 250 mL of beer or lager, one glass of wine, or 20 mL spirits). 13.Mental incapacity or language barriers which preclude adequate understanding or cooperation, unwillingness to participate in the trial, known or suspected not to comply with study directives or not to be reliable or trustworthy, or subject who in the opinion of their general practitioner or the Investigator should not participate in the trial. 14.Clinically significant abnormal laboratory test results during the screening as judged by the Investigator (one retest within a week is permitted, the last result being conclusive). 15.Increased risk of bleeding, e.g. subjects with a history of deep cerebral bleeding or known defects of hemostasis with increased risk of bleeding, as judged by the Investigator. 16.Liver enzymes (ALT and AST) more than twice the upper limit of normal. Parts A and B only 17.Any history of or presence of clinically significant diseases such as cancer, clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases, other major disorders as judged by the Investigator. 18.Supine blood pressure at screening, after resting for 5 min, of > 140 mmHg systolic or > 90 mmHg diastolic (excluding white-coat hypertension; therefore, if a repeat measurement on a second screening visit shows values within the range, the subject can be included in the trial). 19.Intake of anti-inflammatory drugs, OTC drugs or herbal remedies within 14 days before start of treatment. Steroid therapy other than topical application is not allowed. Part C only 20.History of or presence of clinically significant diseases such as cancer, clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases, other major disorders as judged by the Investigator, or significant secondary diabetic complications, such as but not limited to clinically relevant peripheral neuropa;Exclusion criteria: All Parts (A, B and C) 1.Employees or personnel affiliated with the Sponsor or Investigator. 2.Previous participation (randomisation) in this trial. 3.The intake of any investigational drug within one month or five half-lives, whatever is longer, before administration of study drug. 4.A history of significant multiple drug allergies or with a known allergy to the trial product or any medicine chemically related to the trial product, as judged by the Investigator. 5.Clinically significant acute illness within 2 weeks before administration of study drug, including severe infections, as judged by the Investigator. 6.Abnormal and clinically significant ECG at screening. 7.Donation of any blood or plasma in the past month or in excess of 500 mL within the 12 weeks preceding screening. 8.Intake of paracetamol within 7 days before start of treatment. 9.Surgery or trauma with significant blood loss within the last 3 months before administration of study drug. 10.Smokers (negative cotinine test required). 11.A positive result of the human immunodeficiency virus (HIV) 1 and 2 test and/or positive Hepatitis B antigen and/or positive Hepatitis C antibody screen. 12.A history of alcoholism or drug/chemical abuse, or a positive result in the urine/ drug/ breath alcohol screen, or consumption of more than 14 units of alcohol per week (one unit of alcohol equals about 250 mL of beer or lager, one glass of wine, or 20 mL spirits). 13.Mental incapacity or language barriers which preclude adequate understanding or cooperation, unwillingness to participate in the trial, known or suspected not to comply with study directives or not to be reliable or trustworthy, or subject who in the opinion of their general practitioner or the Investigator should not participate in the trial. 14.Clinically significant abnormal laboratory test results during the screening as judged by the Investigator (one retest within a week is permitted, the last result being conclusive). 15.Increased risk of bleeding, e.g. subjects with a history of deep cerebral bleeding or known defects of hemostasis with increased risk of bleeding, as judged by the Investigator. 16.Liver enzymes (ALT and AST) more than twice the upper limit of normal. Parts A and B only 17.Any history of or presence of clinically significant diseases such as cancer, clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases, other major disorders as judged by the Investigator. 18.Supine blood pressure at screening, after resting for 5 min, of > 140 mmHg systolic or > 90 mmHg diastolic (excluding white-coat hypertension; therefore, if a repeat measurement on a second screening visit shows values within the range, the subject can be included in the trial). 19.Intake of anti-inflammatory drugs, OTC drugs or herbal remedies within 14 days before start of treatment. Steroid therapy other than topical application is not allowed. Part C only 20.History of or presence of clinically significant diseases such as cancer, clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases, other major disorders as judged by the Investigator, or significant secondary diabetic complications, such as but not limited to clinically relevant peripheral neuropa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A). 2. To investigate the potential for interaction between EV-077-3201-2TBS and ASA in healthy subjects (Part B). 3. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in type 2 diabetic subjects (Part C). ;Secondary Objective: 1. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet aggregation (Part A). 2. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet function, vascular function, vascular inflammation, vascular oxidative stress, renal function and a selection of exploratory parameters and biomarkers in type 2 diabetic subjects (Part C). 3. To investigate the pharmacokinetics of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A) and type 2 diabetic subjects (Part C). ;Primary end point(s): 1. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A). 2. To investigate the potential for interaction between EV-077-3201-2TBS and ASA in healthy subjects (Part B). 3. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in type 2 diabetic subjects (Part C). ;Timepoint(s) of evaluation of this end point: End of the study.;Main Objective: 1. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A). 2. To investigate the potential for interaction between EV-077-3201-2TBS and ASA in healthy subjects (Part B). 3. To assess the safety and tolerability of multiple doses of EV-077-3201-2TBS over 4 weeks in type 2 diabetic subjects (Part C). ;Secondary Objective: 1. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet aggregation (Part A). 2. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet function, vascular function, vascular in | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet aggregation (Part A). 2. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet function, vascular function, vascular inflammation, vascular oxidative stress, renal function and a selection of exploratory parameters and biomarkers in type 2 diabetic subjects (Part C). 3. To investigate the pharmacokinetics of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A) and type 2 diabetic subjects (Part C).;Timepoint(s) of evaluation of this end point: End of the study.;Secondary end point(s): 1. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet aggregation (Part A). 2. To investigate the effect of multiple doses of EV-077-3201-2TBS on platelet function, vascular function, vascular inflammation, vascular oxidative stress, renal function and a selection of exploratory parameters and biomarkers in type 2 diabetic subjects (Part C). 3. To investigate the pharmacokinetics of multiple doses of EV-077-3201-2TBS over 4 weeks in healthy subjects (Part A) and type 2 diabetic subjects (Part C).;Timepoint(s) of evaluation of this end point: End of the study. | — |
Countries
Germany
Contacts
Public ContactChief Medical Officer;Chief Medical Officer ;
Evolva SA;Evolva SA
Outcome results
None listed