Quantification of the DPP-4 inhibition-mediated enhancement of the activity of the entero-insular axis

• Conditions: Diabetes Type 2; MedDRA version: 9.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus

• Registration Number: EUCTR2008-001663-11-DE
• Lead Sponsor: Diabeteszentrum Bad Lauterberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-10
• Last Update Posted: 3 July 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Visit 1 (Screening):
a. Patient has type 2 diabetes mellitus (T2DM) (according to ADA criteria). Note: an OGTT may be performed to confirm diagnosis of T2DM
b. Patient is = 30 and = 75 years of age on the day of signing informed consent.
c. Patient has a BMI that is = 25 and = 35 kg/m2.
d. Patient is currently not on an OHA medication and has a Screening/Visit 1 HbA1c = 6.5% and = 9% or is on OHA monotherapy with metformin or a sulfonylurea and has a Screening/Visit 1 HbA1c = 6% and = 8.5%
e. Patient is a male, or a female who is unlikely to conceive, as indicated by at least 1 yes” answer to the following questions:
1) Patient is a male.
2) Patient is a surgically sterilized female.
3) Patient is a postmenopausal female = 45 years of age with > 2 years since last menses.
4) Patient is a non-sterilized, premenopausal female and agrees to abstain from heterosexual activity or to use an adequate method of contraception to prevent pregnancy. Note: Acceptable methods of birth control are: hormonal contraceptive, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, or vasectomy.
f. Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
g. Agreement to maintain prior diet and exercise habits during the full course of the study.
h. Ability to comply with all study requirements.

At Visit 3
i. Patient has an FPG of = 110 mg/dL (6.1 mmol/L) and =220 mg/dL (12.2 mmol/L).
Note: If the Visit 3 FPG does not meet this criterion AND is not consistent with the patient's recent fasting SBGM values, a single repeat measurement may be performed at the discretion of the investigator. If repeat value meets FPG inclusion criterion, patient may continue in the study.

At Visit 4
j. Patient is = 80% compliant with study medication during the single-blind placebo run-in (as determined by tablet count).

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

At Visit 1
a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis
b. Patient is assessed by the investigator as possibly having type I diabetes confirmed with a C-peptide = 0.7 ng/mL (0.23 nmol/L). Note: Only patients assessed by the investigator as possibly having type I diabetes should have C-peptide measured at Visit 1.
c. Patient has been taking oral anti-hyperglycemic agent (OHA) within the prior 12 weeks, except metformin or a sulfonylurea.
d. Patient has required insulin therapy within the past 12 weeks. Note: patients who received a brief period of insulin treatment (e.g., several days during a hospitalization) and who are no longer requiring insulin treatment may participate.
Patients Requiring Specific Treatments
e. Patient is on a weight loss program and is not in the maintenance phase, or patient started weight loss medication (e.g., orlistat, sibutramine, or rimonabant) within the prior 8 weeks.
f. Patient is on or likely to require treatment with = 2 consecutive days or repeated courses of pharmacologic doses of corticosteroids, or requires steroid replacement therapy (i.e., in patients with adrenal insufficiency)
Exception: Topical or inhaled corticosteroids are permitted in the study.
g. Patient is being treated with immunosuppressive or immunomodulating agents (e.g., cyclosporine, metotrexate).
h. Patient is currently participating or has participated in a study with an investigational compound or device within 12 weeks or 5 half-lives of signing informed consent.
i. Patient has undergone a surgical procedure within 4 weeks prior to signing informed consent. Exception: Patient with a history of minor surgery (i.e. using local anesthesia, like for removal of basal cell carcinoma, cataract, etc) within 4 weeks of signing informed consent and is fully recovered may participate.
j. Patient has a history of intolerance or hypersensitivity to a DPP- 4- inhibitor or metformin or has any contraindication to DPP-4 inhibitors or metformin based upon label of the country of the investigational site.
Concomitant Disease of Organs and Systems
k. Patient has laboratory values as listed below:
Parameter Values
Creatinine Clearance < 70 mL/min
ALT† > 2 times ULN
AST† > 2 times ULN
TSH Outside of normal range
TG > 600 mg/dL (> 4.5 mmol/L)
MDRD estimated creatinine clearance
† Patients whose serum ALT or AST exceeds this limit may be retested one time if the investigator does not believe the value reflects the patient’s status.
l. Patient has evidence of a significant cardiovascular disorder within 6 months of signing informed consent (e.g. acute coronary syndrome [e.g. MI or unstable angina], new or worsening angina; coronary artery intervention [e.g., CABG or PTCA]; stroke or transient ischemic neurological disorder).
m. Patient has congestive heart failure that requires pharmacological treatment
n. Patient has a systolic blood pressure of = 160 mmHg or diastolic blood pressure of = 95 mmHg. Note: Investigators are encouraged to maximize blood pressure control according to current guidelines. Patient may have blood pressure medication adjusted and be enrolled if repeat blood pressure measurement no longer meets exclusion criterion at Visit 3/Week -2.
o. Patient has a history of malignancy. Exceptions: (1) Patients with adequately treated non-melanomatous skin carcinoma or carcin

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an isoglycemic intravenous glucose load);Secondary Objective: To assess the effect of sitagliptin compared with placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an isoglycemic intravenous glucose load).<br><br>To assess the effect of co-administration of sitagliptin and metformin compared with sitagliptin alone and metformin alone on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an isoglycemic intravenous glucose load).;Primary end point(s): The effect of co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an ‘isoglycemic’ intravenous glucose load).