A study of an experimental new drug to treat diabetes.

Phase 1

• Conditions: Subjects with type 2 diabetes mellitus who are being treated with metformin.; MedDRA version: 14.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2011-000483-94-ES
• Lead Sponsor: GlaxoSmithKline, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-09-15
• Study Completion: 2012-09-17
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria
apply:
1. A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests, with onset at least 6 months prior to Screening. Subjects may be entered if they have stable hypertension or dyslipidemia on therapy. Subjects with other conditions except as noted in the Exclusion criteria may be included only if the investigator and GSK medical monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with study procedures.
2. HbA1c levels ? 7.0 % and ? 9.5%; at Screening.
3. On monotherapy with metformin at the time of screening, and at a total daily dose greater than or equal to 1000 mg for at least 2 months prior to dosing.
4. Fasting plasma glucose level < 13.3 mmol/L (240 mg/dL) at Screening.
5. Male or female between 20 and 70 years of age, inclusive, at the time of signing the informed consent.
6. Fasting Triglycerides lower than 4.52 mmol/L (400 mg/dL).
7. A female subject is able to participate is she if of:
Non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L), or values consistent with applicable lab reference ranges, are confirmatory for women who are not on hormone replacement therapy (HRT). For post-menopausal women taking HRT, a suppressed FSH will be adequate confirmation.
8. Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 3 days after last dose of the study medication.
9. Overweight with BMI ? 25 kg/m2 for non-Asian Indians and ? 24 kg/m2 for Asian-Indian, and < 40 kg/m2.
10. The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
11. Subjects in France will be eligible only if they are affiliated to or a beneficiary of a social security category.
12. Subjects in other countries must meet all local and/or country-specific requirements for registration and reimbursement, as applicable.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Requiring insulin therapy or use of combination oral antidiabetic medications or use of monotherapy other than metformin within the 3 months prior to screening.
2. Past or present disease (other than type 2 diabetes mellitus) that in the opinion of the Investigator may affect the outcome of this study. These diseases include the following but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, gastrointestinal disease and endocrine disease.
3. A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C result within 3 months of screening.
4. Renal impairment as defined by a calculated GFR < 60 mL/min [Cockcroft, 1976]
5. Any concurrent serious illness (e.g., severe COPD, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study.
6. AST, ALT, alkaline phosphatase ? 3ULN and bilirubin ? 1.5xULN (isolated bilirubin > 2xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
7. Significant ECG abnormalities at Screening or Baseline, defined as follows:
Heart Rate < 50 and >100 bpm
PR Interval <120 and > 220 ms
QRS duration < 70 and >120 ms
QTC Interval (Bazett?s, or Frederica?s if it is
automatically calculated)*
> 450 ms (>480 msec in subjects with partial
Right Bundle Branch Block)
Subjects with Left Bundle Branch Block are excluded from the study. Subjects with partial Right Bundle Branch Block may be considered for inclusion following consultation with the GSK Medical Monitor.
* Note that if ECG abnormalities are identified, the average of 3 values taken approximately 5 minutes apart should be used to determine eligibility.
8. Systolic blood pressure greater than 160 mmHg, or diastolic blood pressure greater than 100 mmHg at Screening.
9. History of uric acid kidney stone, and being treated with drugs for hyperuricemia including Allopurinol or Probenicid.
10. History of peptic ulcer disease (PUD) and/or other gastrointestinal bleeding within the 12 months prior to screening.
11. Use of the following blood pressure medications or other medications that are renally excreted via OAT is prohibited: Enalapril (at any dose), Losartan (at any dose), Captopril (at any dose) and ongoing use of niacin or niacin containing medication. Please refer to Section 9.2 of protocol or consult GSK medical monitor.
12. History of myopathy or CPK value > 3 x ULN at screening.
13. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
14. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
15. Any change in diet, exercise habits or smoking status within six weeks prior to screening. Any subject that cannot refrain from smoking while in the unit must be excluded.
16. History of sensitivity to any of the study medications, including sitagliptin or metformin, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
17. The subject has a positive

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified