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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EV-077 in Type 2 Diabetic Subjects

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ClinicalTrials.gov Identifier: NCT01551381
Recruitment Status : Terminated (Interim review indicated that the dose selected was too high for diabetics)
First Posted : March 12, 2012
Last Update Posted : June 17, 2013
Sponsor:
Information provided by (Responsible Party):
Evolva SA

Tracking Information
First Submitted Date  ICMJE March 8, 2012
First Posted Date  ICMJE March 12, 2012
Last Update Posted Date June 17, 2013
Study Start Date  ICMJE January 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2012)
Platelet aggregation [ Time Frame: 8 days ]
Measured at Day 8 by Multiplate® with arachidonic acid as the agonist
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01551381 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2012)
  • 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)
  • 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
  • Diabetic state [ Time Frame: Baseline, 2 weeks and 4 weeks ]
    Change from baseline in fasting plasma glucose and HbA1c
  • Renal function [ Time Frame: Baseline, 2 weeks and 4 weeks ]
    Change from baseline in urinary albumin excretion, creatinine clearance and exercise-induced microalbuminuria
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2012)
  • Platelet aggregation [ Time Frame: 4 weeks ]
    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)
  • Vascular inflammatory state [ Time Frame: 4 weeks ]
    Changes from baseline in markers of platelet function, vascular function, vascular inflammation and vascular oxidative stress
  • Diabetic state [ Time Frame: 4 weeks ]
    Change from baseline in fasting plasma glucose and HbA1c
  • Renal function [ Time Frame: 4 weeks ]
    Change from baseline in urinary albumin excretion, creatinine clearance and exercise-induced microalbuminuria
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EV-077 in Type 2 Diabetic Subjects
Official Title  ICMJE 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.
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes
Intervention  ICMJE
  • Drug: EV-077
    twice daily oral administration
    Other Name: EV-077-3201-2TBS
  • Drug: Placebo
    twice daily oral administration
Study Arms  ICMJE
  • Experimental: EV-077
    Oral administration
    Intervention: Drug: EV-077
  • Placebo Comparator: Placebo
    Oral administration
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 3, 2013)
33
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2012)
64
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01551381
Other Study ID Numbers  ICMJE EV077/C005
2011-003808-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Evolva SA
Study Sponsor  ICMJE Evolva SA
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas Jax, MD Profil Institut für Stoffwechselforschung GmbH, Germany
PRS Account Evolva SA
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP