A Multi-Center, Double-Blind, Parallel-Group, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Denagliptin in Subjects With Type 2 Diabetes Mellitus”

Conditions: Type 2 Diabetes Mellitus
MedDRA version: 8.0Level: LLTClassification code 10045242

Registration Number: EUCTR2006-002157-79-FI

Lead Sponsor: GlaxoSmithKline

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 480

Inclusion Criteria

Subjects will be entered into this study only if they meet all of the following criteria:
1.Subjects with T2DM as defined by the criteria of the American Diabetes Association and recognized by World Health Organization (WHO) Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [American Diabetes Association, 2004a] for at least 2 months preceding screening.
2.Concurrent T2DM therapy:
·DIET AND EXERCISE ONLY (TREATMENT NAÏVE): Must be diet and exercise treated; must not have taken anti-diabetic medication for at least 3 months prior to the Pre-screening Visit (Visit 1)
OR
·MONOTHERAPY: Not taking more than 1 oral anti-diabetic agent, and willing to stop treatment at Screening (Visit 2)
·Previous diabetes monotherapy will be limited to: sulfonylureas, glitinides, biguanides, or a-glucosidase inhibitors, such as acarbose. A thiazolidinedione is only acceptable if it has been stopped 3 or more months prior to screening. Monotherapy with a fixed-dose combination drug is not allowed. Subjects must not have been taking any oral anti-diabetic combination therapy (including with a fixed dose combination drug) for at least 3 months prior to the screen visit.
3.Glycemic parameters:
·HbA1c level at Pre-screening (Visit 1)
·For subjects treated with oral monotherapy: =7.0% and £8.5%;
·For subjects treated with diet and exercise only: =7.5% and £10.0%.
·Fasting glucose level at the Screening Visit (Visit 2) £260 mg/dL (14.4 mmol/L)
4.Men and women who are 18 to 75 years of age inclusive at the time of Screening (Visit 2).
5.BMI =20 and =40 kg/m2.
6.If female, is eligible to enter and participate in this study:
·If of non-childbearing potential (i.e., physiologically incapable of becoming pregnant [tubal ligation), including any female who is post-menopausal [>1 year without menstrual period]); or,
·If of child-bearing potential, has a negative serum pregnancy test at Screening (Visit 2) and Baseline (Week 0, Visit 5) and:
Has a male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject, or
If she uses double-barrier methods of contraception; condoms (with spermicide) and intrauterine device (IUD) are acceptable, or
If she uses hormonal contraceptives (oral, depots, patches, etc.) with double-barrier methods of contraception as outlined above, or
If she abstains from sexual intercourse, or
If she is with a same-sex partner and does not participate in bisexual activities where there is any risk of pregnancy.
7.Informed Consent: a signed and dated written consent obtained from the subject before any study-related procedures are performed
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

bjects will be entered into this study only if they meet none of the following criteria:
1.Metabolic disease including but not limited to:
·Diagnosis of type 1 diabetes mellitus or ketoacidosis or
·Uncorrected thyroid dysfunction. (Note: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to Screening [Visit 2], and who have a screening thyroid-stimulating hormone [TSH] within the limits of normal may participate).
·Previous use of insulin:
-Within 3 months prior to screening;
-For >2 weeks when used for acute illness in the last 12 months prior to Screening (Visit 2) or
-Used for more than 1 year when associated with gestational diabetes mellitus;
2.History of clinically significant cardiovascular disease, including:
·Documented myocardial infarction, stroke, or transient ischemic attack in the past year;
·Coronary revascularization including percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery in the previous year;
·Unstable angina;
·Clinically significant arrhythmia or valvular heart disease;
·Congestive heart failure classified as New York Heart Association (NYHA) Class III or IV heart failure, NYHA Functional Classification)];
·Blood pressure >150/100 mmHg or heart rate >100 beats/minute at Screening. Subjects using antihypertensives must be on stable doses during the 3 months prior to Screening;
·A QTc interval (Bazett’s) =440 msec in males and =450 msec in females at Screening (Visit 2); or
·Other clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of safety and/or efficacy data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.
3.Is currently lactating, pregnant, or actively trying to become pregnant.
4.Has a significant renal impairment as defined by serum creatinine >2 mg/dL (>176 mmol/L).
5.History of significant co-morbid diseases active within the last 6 months (e.g., gastrointestinal disease, malignancy).
6.History of pancreatitis.
7.Subjects with an ALT/AST >2.5 x the upper limit of the normal (ULN) reference range or total bilirubin >1.5 x ULN, other than Gilbert’s syndrome.
8.History of alcohol or substance abuse within the past year, as determined by the Investigator or a positive urine drug screen at Screening (Visit 2) or during treatment:
·Unwilling to refrain from the use of excessive alcohol or illicit drugs and adhere to other protocol-stated restrictions while participating in the study;
·History of alcohol abuse defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine; or
·The Investigator should exercise his/her medical judgment to determine if a urine drug screen is indicated.
9.Is currently taking prohibited concomitant medications listed in Appendix 1.
10.Known allergy to any of the capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contradicts participation.
11.Received treatment with an investigational drug or participated in any other clinical trial during the previous 3 months.
12.Clinically significant anemia (i.e., hemoglobin <12.0 g/dL [<120.0 g/L] for males and <