Overview

Antidiabetic Effects of Adding a DPP-4 Inhibitor to Pre-Existing Treatment With an Incretin Mimetic in Patients With T2D

Status:
Completed
Trial end date:
2015-06-01
Target enrollment:
0
Participant gender:
All
Summary
Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Michael A. Nauck
Treatments:
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Incretins
Liraglutide
Metformin
Sitagliptin Phosphate
Criteria
Inclusion Criteria:

- Signed & dated written informed consent

- Male & female subjects with a diagnosis of type 2 diabetes mellitus according to ADA
criteria at least 4 months prior to screening

- Medical history without major pathology (with the exception of type 2 diabetes) as
judged by the investigator

- On a stable regimen of metformin for at least 1 month and liraglutide 1.2 mg for at
least 1 week at the time-point of randomisation.

- Age: 25 - 75 years, both inclusive

- Body mass index (BMI): 22 - 40kg/m^2, both inclusive

- HbA1c ≥ 6.5 and ≤ 8.5% (≥ 7.0 and ≤ 8.5% for patients without previous liraglutide
treatment)

- Female must be post-menopausal, surgically sterilized or practicing an effective birth
control

Exclusion criteria

- Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or
secondary forms of diabetes such as due to pancreatitis

- Current or previous treatment with insulin therapy (except for treatment at diabetes'
diagnosis, within a clinical trial, for surgical procedures or during an acute
illness, and no insulin administration within the 6 months before screening)

- Treatment with any hypoglycaemic medication other than metformin and liraglutide
within one month prior to screening

- Known of diabetic gastroparesis and / or prokinetic therapy

- Subjects that underwent surgery of the upper gastrointestinal tract

- Women who are pregnant, intending to become pregnant during the study period,
currently lactating females, or women of child-bearing potential not using highly
effective, medically approved birth control methods

- Any severe medical or surgical history of conditions likely to confound study
assessments or study endpoints, for example but not limited to haemoglobinopathies,
inflammatory bowel disease, cystic fibrosis, bariatric surgery and/or any surgery
shortening the intestine, history of lactose intolerance, lactose- or
glucose-galactose-malabsorption

- A suspicion of medullary thyroid cancer or a multiple endocrine neoplasia

- A personal or family history of medullar thyroid cancer or a multiple endocrine
neoplasia

- Serious and/or unstable coronary heart disease (unstable angina, myocardial infarction
within the preceding 6 months), congestive heart failure of New York Heart Association
Class III or worse (severe limitation of physical activity; physical activity of low
intensity resulting in fatigue, palpitation, or dyspnoea), second/third degree heart
block, superior vena cava syndrome, uncontrolled hypertension, history of congenital
QT-syndrome within family, history of stroke (within the preceding 6 months) or
serious peripheral vascular disease

- History of arrhythmia (multifocal premature ventricular contractions, bigeminy,
trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is
symptomatic or requires treatment (grade 3), left bundle branch block, or asymptomatic
sustained ventricular tachycardia are not allowed

- Marked diabetic complications: severe autonomic or sensory neuropathy including
previously diagnosed gastroparesis; proliferative retinopathy

- Any respiratory disease leading to respiratory insufficiency and/or depression
including but not limited to clinically significant: bronchial asthma, chronic
obstructive pulmonary disease, that might impact to the breath test, as judged by the
investigator

- Clinically significant vital signs including known bradycardia with pulse rate <
50/min or 12-lead ECG findings including QTc (corrected QT interval) > 450 msec for
males or QTc > 470 msec for women

- Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or
coagulation screening tests, as judged by the Investigator

- Moderate or severe renal dysfunction defined as an estimated creatinine clearance
(MDRD equation) GFR (glomerular filtration rate) <50 ml/min.

- Clinical or laboratory evidence of hepatic dysfunction or disease; laboratory evidence
defined as any of the following parameters: alkaline phosphatase, ALT , AST or
bilirubin > 3x ULN (upper Limit of normal). Isolated mild rise in bilirubin considered
to be due to Gilbert's condition is allowed

- Uncontrolled high blood pressure (DBP (diastolic blood pressure) > 95 mmHg and/or SBP
(systolic blood pressure) > 160 mmHg), unless clearly documented to be white-coat
hypertension

- History of any psychiatric condition that might impair the subject's ability to
understand or to comply with the requirements of the study or to provide informed
consent

- History of relevant drug and/or food allergies or a history of severe anaphylactic
reaction

- Currently active or history of alcohol abuse (defined as an intake of more than 24
units of alcohol per week; one unit of alcohol equals approximately 250 mL of beer,
100 mL of wine or 35 mL of spirits) or drug addiction (including soft drugs like
cannabis products)

- Use of concomitant medication which would be likely to interact with metformin,
sitagliptin or liraglutide (according to the subject information leaflet).
Participation in another study within the 3 months preceding screening or 5-half-lives
of drug studied, whichever is longer, prior to study drug administration

- Malignancy within 5 years of study start, except for successfully treated local basal
cell carcinomas

- Known to be positive for Hepatitis B surface antigen or Hepatitis C antibodies (or
diagnosed with active hepatitis according to local practice)

- Subject who has donated or lost > 500 mL blood within 3 months prior to screening &
has a Hb < 14 g/dl at screening

- History of hypersensitivity to the study drug or any of the excipients or to medicinal
products with similar chemical structures

- Veins unsuitable for repeated venipuncture