Clinical trial NCT01031108 (phase 1, 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:

        - Ambulatory male and female subjects (of any race) either with type 2 diabetes or
        otherwise healthy cigarette smokers (≥ 10 cigarettes/day for at least 1 year) within the
        age range of 18-70 years (inclusive) at the time of Screening.

          -  If a subject is diabetic, HbA1c at Screening is < 9.0%

          -  If a subject is diabetic, fasting plasma glucose (FPG) ≤ 13.875 mmol/L (≤ 250 mg/dL).

          -  If a subject is diabetic, an official diagnosis of type 2 diabetes must be documented
             for at least 6 months prior to first dose of test article.

          -  If a subject is diabetic, subject must be on an existing, stable, hypoglycemic therapy
             or a stable dietary regimen to control their disease for at least 3 months prior to
             Screening.

        Note: If a subject is a diabetic and a smoker, then they are not eligible for the trial. A
        minimum 5 year non-smoking history is required for all type 2 diabetic subjects to be
        enrolled into the study.

          -  Female subjects of child-bearing potential, willing to use reliable contraception (see
             Section 5.10) for the duration of the study, through to the 30 day safety follow up
             visit (a female of child-bearing potential is defined as any female, regardless of her
             age with functioning ovaries and no documented impairment of oviductal or uterine
             function that would cause sterility. Females with oligomenorrhea or who are
             perimenopausal, and young females who have begun to menstruate are considered to be of
             child-bearing 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 study drug.

          -  Willingness to provide written informed consent to participate in the study.

          -  Subject may be on concomitant treatments for other conditions, provided the medical
             condition necessitating the treatment and therapy is stable for at least 3 months
             prior to screening and the treatment is not counterindicated by the study protocol.

          -  Subject is not currently on a therapeutic regimen of ACE inhibitors, anti-coagulants,
             anti-platelets, or any other medications or treatments which may influence coagulation
             (with the exception of 81 mg or less of aspirin/acetylsalicylic acid daily).

          -  Body Mass Index (BMI) of 18.5-38 kg/m^2 (inclusive).

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

          -  Absence of significant disease (other than type 2 diabetes) or clinically significant
             abnormal laboratory values on the laboratory evaluations, medical history, or physical
             examination during screening; normal end organ function at the discretion of the
             principal investigator.

          -  Negative test result at screening for HIV 1 and 2.

          -  Negative test result at screening for hepatitis B & C virus.

          -  Have a normal 12-lead electrocardiogram (ECG) or one with changes considered to be
             clinically insignificant on medical review. QTcB must be < 450 msec for males and
             females. QTcB must be <480 msec in subjects with Bundle Branch Block.

          -  Comprehension of the nature and purpose of the study and compliance with the
             requirements of the entire protocol.

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

        Exclusion Criteria:

          -  If diabetic, any major illness in the past 3 months or any significant ongoing chronic
             medical illness not related to diabetes which in the opinion of the principal
             investigator or medical monitor could risk subject safety or interpretation of the
             results.

          -  If an otherwise healthy cigarette smoker, any major illness or injury in the past 3
             months or any significant ongoing chronic medical illness (including diabetes) 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 alkaline phosphatase and/or bilirubin ≥ 1.5 x
             ULN (an isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and
             direct bilirubin is <35%), serum creatinine level of ≥ 123.76 µmol/L (≥ 1.4 mg/dL ) in
             females and ≥ 132.60 µmol/L (≥ 1.5 mg/dL ) in males, and > 2 × ULN for liver
             transaminases (ALT and AST), respectively.

          -  History of or current gastrointestinal diseases or surgeries influencing drug
             absorption, except for appendectomy.

          -  History, within 3 years, of drug abuse (including benzodiazepines, opioids,
             amphetamine, cocaine, and THC).

          -  History of alcoholism (more than 2 years), moderate drinkers (more than three drinks
             per day) or having consumed alcohol within 48 hours prior to first dose of test
             article (one drink is equal to one unit of alcohol [one glass wine, half pint beer,
             one measure of spirit]).

          -  Participation in any clinical trial within the past 3 months prior to the first dose
             of test article in the current study.

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

          -  Donation of blood or loss of blood (greater than 500 mL) within 3 months prior to
             receiving the first dose of test material.

          -  Use of any dietary or herbal supplements within 2 weeks prior the first dose of study
             drug, with the exception of an Investigator approved vitamin.

          -  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 or squamous cell carcinoma of the skin or carcinoma in
             situ).

          -  A positive pre-study drug screen.