- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01551381
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EV-077 in Type 2 Diabetic Subjects
Double-blind, Controlled Study in Healthy and Type 2 Diabetic Subjects to Assess Safety, Tolerability and Pharmacokinetics of 28 Days EV-077 Treatment, and the Effects on Platelet Function, Vascular Inflammation and Oxidative Stress.
The principal objective of this study is to evaluate the safety and tolerability of repeated doses of EV-077-3201-2TBS given to diabetic subjects over a 4 week treatment period. The secondary aim of this initial Phase IIa study is to evaluate the effect of multiple oral 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, as well as multiple dose pharmacokinetics in diabetic subjects.
In order to ensure the safety of the diabetic subjects, initial parts of the study will evaluate the safety and tolerability of EV-077-3201-2TBS. In Part A, the safety of different doses EV-077-3201-2TBS will be investigated in healthy subjects treated for 4 weeks. In parallel, Part B will investigate potential interactions between EV-077-3201-2TBS and ASA in healthy subjects. Part C will then investigate the safety, pharmacokinetics and pharmacodynamics of EV-077-3201-2TBS in type 2 diabetic subjects with and without concomitant ASA therapy.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Neuss, Germany
- Profil Institut für Stoffwechselforschung GmbH
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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).
- Body mass index (BMI) between 25.0 and 40.0 kg/m2 (both inclusive).
- 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.
- HbA1c ≥ 6.0 and ≤ 9.0 %.
- History of hyperlipidaemia, 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).
- 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.
Exclusion Criteria:
- Abnormal and clinically significant ECG at screening.
- Donation of any blood or plasma in the past month or in excess of 500 mL within the 12 weeks preceding screening.
- Intake of paracetamol within 7 days before start of treatment.
- Surgery or trauma with significant blood loss within the last 3 months before administration of study drug.
- Smokers (negative cotinine test required).
- 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).
- Increased risk of bleeding, e.g. subjects with a history of deep cerebral bleeding or known defects of haemostasis with increased risk of bleeding, as judged by the Investigator.
- 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 neuropathy, retinopathy, diabetic foot ulcers, as judged by the Investigator.
- Supine blood pressure at screening, after resting for 5 min, of > 160 mmHg systolic or > 95 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).
- Type 1 diabetes mellitus.
- Intake of anti-inflammatory drugs except ASA (dose 75-125mg/day stable for the previous 3 months) within 14 days before start of treatment. Steroid therapy other than topical application is not allowed.
- Any treatment with diuretics (hydrochlorothiazide is allowed)
- Liver enzymes (ALT and AST) more than 1.5 times the upper limit of normal.
- Any contraindication for a therapy with ASA such as allergy to ASA, including asthma, acute gastric ulcers, haemorrhagic diathesis, renal or liver insufficiency, or heart failure.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Oral administration
|
twice daily oral administration
|
Experimental: EV-077
Oral administration
|
twice daily oral administration
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Platelet aggregation
Time Frame: 8 days
|
Measured at Day 8 by Multiplate® with arachidonic acid as the agonist
|
8 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Platelet aggregation
Time Frame: Days 1, 2, 8, 15, 22 and 29
|
Measured at multiple time points by Multiplate (using arachidonic acid, collagen, U-46619 and ADP as agonists) and the Born method (using arachidonic acid, collagen and ADP as agonists)
|
Days 1, 2, 8, 15, 22 and 29
|
Vascular inflammatory state
Time Frame: Baseline, 2 weeks and 4 weeks
|
Changes from baseline in markers of platelet function, vascular function, vascular inflammation and vascular oxidative stress
|
Baseline, 2 weeks and 4 weeks
|
Diabetic state
Time Frame: Baseline, 2 weeks and 4 weeks
|
Change from baseline in fasting plasma glucose and HbA1c
|
Baseline, 2 weeks and 4 weeks
|
Renal function
Time Frame: Baseline, 2 weeks and 4 weeks
|
Change from baseline in urinary albumin excretion, creatinine clearance and exercise-induced microalbuminuria
|
Baseline, 2 weeks and 4 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Thomas Jax, MD, Profil Institut für Stoffwechselforschung GmbH, Germany
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- EV077/C005
- 2011-003808-20 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes
-
Antonio Di MauroCompletedType-2 DiabetesItaly
-
DiaMedica Therapeutics IncCompletedDiabetes Type 2Netherlands
-
RenJi HospitalUnknownType 2 Diabetes.China
-
University of Erlangen-Nürnberg Medical SchoolCompletedType 2-diabetesGermany
-
Chengdu Brilliant Pharmaceutical Co., Ltd.Not yet recruitingType 2 Diabetes Mellitus
-
Nanjing First Hospital, Nanjing Medical UniversityRecruitingType 2 Diabetes MellitusChina
-
Xiangya Hospital of Central South UniversityRecruitingType 2 Diabetes MellitusChina
-
University of Alabama at BirminghamCompletedType 2 Diabetes MellitusUnited States
-
Imperial College LondonAstraZeneca; Huma; North West London Collaboration of CCGs (NWL CCGs); Imperial...CompletedType 2 Diabetes MellitusUnited Kingdom
-
Universiti Sains MalaysiaCompleted
Clinical Trials on EV-077
-
McGuire InstituteDentsply Sirona ImplantsRecruitingPartially Edentulous Maxilla or MandibleUnited States
-
University Hospital, GrenobleCommissariat A L'energie AtomiqueRecruitingVery Early Stage of Parkinson's DiseaseFrance
-
National Taiwan University HospitalUnknownAtrophy of Edentulous Alveolar RidgeTaiwan
-
Peking UniversityRecruitingAdvanced or Late Stage Gastrointestinal CancerChina
-
Dentsply Sirona Implants and ConsumablesCompletedDental ImplantsUnited States, Belgium, Canada, Finland, Germany, Sweden
-
Dentsply Sirona Implants and ConsumablesActive, not recruitingJaw, Edentulous, PartiallyUnited States, Belgium, Germany, Italy, Netherlands
-
Dentsply Sirona Implants and ConsumablesActive, not recruitingJaw, EdentulousGermany, Switzerland, United Kingdom
-
AtaCor Medical, Inc.CompletedVentricular Fibrillation | Ventricular Tachycardia | Ventricular ArrhythmiaParaguay
-
Shen LinRecruitingImmunotherapy | Advanced Gastric AdenocarcinomaChina
-
Medical University of GrazRecruiting