Antidiabetic Effects of Adding a DPP-4 Inhibitor to Pre-E... | NCT01937598

NCT01937598

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2013-001764-35	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
Sitagliptin, then Placebo	Experimental		Drug: Placebo Other: Mixed meal test Drug: Liraglutide Drug: Sitagliptin
Placebo, then Sitagliptin	Experimental		Drug: Placebo Other: Mixed meal test Drug: Liraglutide Drug: Sitagliptin

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Patients administered a single dose of placebo during a mixed meal challenge.	Placebo, then Sitagliptin Sitagliptin, then Placebo

Measure	Description	Time Frame
Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)	Incremental area under the plasma glucose (BG) concentration-time profile (AUC) immediately before to 300 min after a mixed meal test. In addition, the time course of BG values will be analysed with an ANCOVA model for repeated measurements with placebo baseline values as covariate. Time points to create the curce were 0, 15, 30, 45, 60, 90, 120, 150, 180, 240 and 300 minutes post mixed meal test.	0 to 300 min post mixed meal test

Measure	Description	Time Frame
AUC Plasma Glucose	Incremental AUC from 0 to 300 min	Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Insulin		Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)

Eligibility Module

Eligibility 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

Name	Affiliation	Role
Michael A. Nauck, Prof. Dr.	Diabeteszentrum Bad Lauterberg	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Diabeteszentrum Bad Lauterberg		Bad Lauterberg im Harz		37431	Germany

ID	Title	Description
FG000	Sitagliptin, Then Placebo	Participants first received Sitagliptin tablet before mixed meal test, after washout they then received Placebo before the mixed meal test.
FG001	Placebo, Than Sitagliptin	Participants first received Placebo tablet before mixed meal test, after washout they then received Sitagliptin before the mixed meal test.

ID	Title	Description
BG000	All Study Participants	All study participants (cross-over design) received all interventions.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)

Incremental area under the plasma glucose (BG) concentration-time profile (AUC) immediately before to 300 min after a mixed meal test. In addition, the time course of BG values will be analysed with an ANCOVA model for repeated measurements with placebo baseline values as covariate. Time points to create the curce were 0, 15, 30, 45, 60, 90, 120, 150, 180, 240 and 300 minutes post mixed meal test.

Posted

Mean

Standard Error

[mg*min/dL]

0 to 300 min post mixed meal test

ID	Title	Description
OG000	Sitagliptin	Substance: Sitagliptin phosphate H2O Pharmaceutical form: tablets Source: MSD SHARP & DOHME GMBH, Doses: 100 mg, Route of administration: p.o. as a tablet Sitagliptin Mixed meal test: Subjects will be instructed to consume the mixed meal test within 20 minutes. The exact start and stop time of the mixed meal test consumption will be recorded in the CRF(case report form). The mixed meal test procedures will be identical for all subjects randomised in the study. To detect the plasma glucose excursion after mixed meal test, plasma glucose will be closely monitored Liraglutide: Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week) that will be continued for the entire duration of the study.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sitagliptin	Substance: Sitagliptin phosphate 1H2O Pharmaceutical form: tablets Source: MSD SHARP & DOHME GMBH, Doses: 100 mg, Route of administration: p.o. as a tablet Sitagliptin Mixed meal test: Subjects will be instructed to consume the mixed meal test within 20 minutes. The exact start and stop time of the mixed meal test consumption will be recorded in the CRF. The mixed meal test procedures will be identical for all subjects randomised in the study. To detect the plasma glucose excursion after mixed meal test, plasma glucose will be closely monitored Liraglutide: Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week) that will be continued for the entire duration of the study.

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D000069450	Liraglutide
D000068900	Sitagliptin Phosphate

ID	Term
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones