Clinical trial NCT01018017 (phase 2, status: completed)
Conditions: diabetes mellitus, type 2
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: placebo, srt2104
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CC1=C(SC(=N1)C1=CC=CN=C1)C(=O)NC1=CC=CC=C1C1=CN2C(CN3CCOCC3)=CSC2=N1
Eligibility criteria:

        Inclusion Criteria:

          -  Able and willing to provide written informed consent to participate in the study

          -  Ambulatory male and female subjects (of any race) with T2D within the age range of
             18-65 years (inclusive) at the time of screening

          -  All female subjects must be of non-childbearing potential. All male subjects must
             agree with their partners to use double-barrier birth control or abstinence while
             participating in the study and for 12 weeks following the last dose of investigational
             product. For the purposes of this study, non-childbearing is defined as:

               -  Amenorrheic for at least 12 consecutive months; menopausal status in amenorrheic
                  females will be confirmed by demonstrating levels of follicle stimulating hormone
                  (FSH) >40-138 mIU/mL and estradiol < 30 pg/mL at entry. In the event a subject's
                  menopause status has been clearly established (for example, the subject indicates
                  she has been amenorrheic for 10 years), but FSH and/or estradiol levels are not
                  consistent with a post-menopausal condition, determination of subject eligibility
                  will be at the discretion of the principal investigator with agreement of the
                  independent medical monitor

               -  At least 6 weeks post-surgical bilateral oophorectomy (with or without
                  hysterectomy) or post tubal ligation

          -  The subject must be on stable metformin monotherapy for a minimum of 3 months prior to
             the Screening visit.

          -  HbA1c of 6.5%-9.5% (inclusive)

          -  Body Mass Index (BMI) of 22-38 kg/m^2 (inclusive)

          -  Resting supine blood pressure (BP) < 160/90 mmHg

          -  Have a normal 12-lead electrocardiogram (ECG) or one with changes considered to be
             clinically insignificant on medical review and QTc intervals as defined below:

               -  QTcB must be <450 msec for males and <470 msec for females (based on single or
                  average QTc value of triplicate ECGs obtained over a brief period)

               -  QTcB must be <480 msec in subjects with Bundle Branch Block

          -  Comprehension of the nature and purpose of the study and able to comply with the
             protocol requirements

          -  Able to communicate in person and by telephone in a manner that allows all protocol
             procedures to be carried out safely and reliably in the opinion of the investigative
             site staff

        Exclusion Criteria:

          -  Any major illness in the 3 months prior to study entry or any significant ongoing
             chronic medical illness not related to diabetes (e.g., recent myocardial infarction,
             unstable angina, stroke, or transient ischemic attack) which in the opinion of the
             principal investigator or medical monitor could risk subject safety or interpretation
             of the results

          -  Renal or liver impairment, defined as:

               -  Serum creatinine level of ≥ 1.4 mg/dL for females and ≥ 1.5 mg/dL for males

               -  AST and ALT ≥ 2xULN

               -  alkaline phosphatase and bilirubin > 1.5xULN (an isolated bilirubin >1.5xULN is
                  acceptable if bilirubin is fractionated and direct bilirubin is <35%)

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months of Screening

          -  A positive test for HIV antibody

          -  History of or current gastrointestinal diseases influencing drug absorption as judged
             by the investigator

          -  Significant history of alcoholism or drug/chemical abuse, or a positive result of the
             urine drug/alcohol screen at the Screening Visit, or consuming more than 28 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)

          -  Participation in any clinical trial within 3 months prior to the first dose of
             investigational product in the current study

          -  History of difficulty in donating blood or accessibility of veins in left or right arm

          -  Donation or loss of blood (more than 500 mL) within 3 months prior to receiving the
             first dose of investigational product

          -  Use of any prescription drug therapy, with the exception of any prescription
             medication administered at a stable dose for at least 6 weeks prior to Screening,
             provided the medication is not contraindicated by the metformin label (see Appendix A
             for Glucophage® Summary of Product Characteristics)

          -  Use of any anti-diabetic therapy other than metformin, within 3 months of the first
             dose of investigational product

          -  Use of any dietary or herbal supplements within 3 weeks prior to the first dose of
             investigational product

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or medical
             monitor, contraindicates their participation

          -  Active neoplastic disease or history of neoplastic disease within 5 years of study
             entry (except for basal cell carcinoma of the skin or carcinoma in situ)

          -  Increased risk of thrombosis, e.g., subjects with a history of deep leg vein
             thrombosis or family history of deep leg vein thrombosis, as judged by the
             investigator