A Study Comparing the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-142)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01582308
• Date of registration: 19/04/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: A Study Comparing the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-142)
• Scientific title: A Study to Assess and Compare the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Patients With Type 2 Diabetes Mellitus
• Date of first enrolment: June 21, 2012
• Target sample size: 22
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01582308
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Moldova, Republic of

Key inclusion & exclusion criteria

Inclusion Criteria:

- female participants of reproductive potential must not be pregnant and agree to use
(and/or have their partner use) two acceptable methods of birth control beginning at
least 2 weeks prior to administration of the first dose of study drug until at least 2
weeks after the last administration of study drug

- has a body mass index between 18 and 43 kg/m^2 inclusive

- has a clinically confirmed diagnosis of T2DM

- is not currently receiving any oral antihyperglycemic medications and has a screening
visit hemoglobin A1c (HbA1c) between 6.5% and 10% inclusive

- must not have been previously treated with a DPP-4 inhibitor or glucagon-like
peptide-1 analogs within 12 weeks of prestudy visit

- has fasting plasma or serum glucose (FPG) =200 mg/dL (11.1 mmol/L) at screening and
randomization

- is a non-smoker or has not used nicotine or nicotine-containing products for at least
approximately the last 6 months

- is willing to follow the American Heart Association weight maintaining diet and
exercise program or equivalent beginning 2 weeks prior to administration of first dose
of study drug and throughout the study until the poststudy visit

- agrees to refrain from the consumption of grapefruit and grapefruit juice for at least
2 weeks prior to the start of the study and throughout the study

- agrees to refrain from the consumption of all fruit juices periodically throughout the
study

Exclusion Criteria:

- is mentally or legally incapacitated, has significant emotional problems at the time
of prestudy visit or expected during the conduct of the study or has a history of a
clinically significant psychiatric disorder over the last 5 years

- has an estimated creatinine clearance of =60 mL/min

- has a history of stroke, chronic seizures, or major neurological disorder

- has a history of clinically significant endocrine, gastrointestinal, cardiovascular,
hematological, hepatic, immunological, renal, respiratory, or genitourinary
abnormalities or diseases (with the exception of stable thyroid disease, T2DM and
typical associated diseases such as hypertension and hyperlipidemia)

- must not have been previously treated with any regimen that includes insulin (injected
or inhaled) for at least 3 months

- has a history of type 1 diabetes mellitus and/or history of ketoacidosis, or C peptide
=0.8 ng/mL (=0.26 nmol/L); or secondary forms of diabetes, acute metabolic diabetic
complications or evidence of significant diabetic complications (i.e. retinopathy,
neuropathy, nephropathy)

- has a history of neoplastic disease (including leukemia, lymphoma, malignant
melanoma), or myeloproliferative disease

- is on a weight loss program and is not in the maintenance phase, or participant has
been treated with a weight loss medication within 8 weeks of screening

- anticipates the use of any new medication(s), including prescription and
non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to
administration of the initial dose of study drug and throughout the study until the
poststudy visit

- anticipates any change in dose of current stable medications

- has donated or lost 1 unit of blood within 4 weeks of the prestudy visit

- has had major surgery within 30 days prior to screening or has planned major surgery

- has a history of uncontrolled hypertension

- is taking a medication which is not permitted in the study to treat a co-morbid
condition, including but not limited to cytochrome P450 3A4/5 inhibitors and inducers,
P-glycoprotein 1 inhibitors, and human organic anion transporter 3 inhibitors

- consumes excessive amounts of alcohol, coffee, tea, cola, or other caffeinated
beverage daily

- has a history of significant multiple and/or severe allergies, or has had an
anaphylactic reaction or significant intolerability to prescription or
non-prescription drugs or food

- is currently a regular user (including "recreational use") of any illicit drugs or has
a history of drug (including alcohol) abuse within approximately the past 6 months

- is a nursing mother



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus

Intervention(s)

Drug: Vildagliptin 50 mg

Drug: Placebo

Drug: Sitagliptin 100 mg

Drug: Vildagliptin 50 mg BID

Drug: Saxagliptin 5 mg

Primary Outcome(s)

Percent Inhibition of Dipeptidyl Peptidase IV (DPP-4) Activity at Trough [Time Frame: 24 hours following the final morning dose on Day 5]

Secondary Outcome(s)

Pharmacokinetic Analysis: Area Under the Curve 0-24 Hours (AUC 0-24hr) [Time Frame: Predose (0 Hours) and 0.5, 1, 2, 4, 8, 12, 13 (vildagliptin 50 mg BID only), 14 (vildagliptin 50 mg BID only), 16, 20 and 24 hours after the morning dose on Day 5]

Pharmacokinetic Analysis: Area Under the Curve 0-12 Hours (AUC 0-12hr) for Vildagliptin 50 mg BID [Time Frame: Predose (0 hours) and 0.5, 1, 2, 4, 8 and 12 hours after the morning dose on Day 5]

Pharmacokinetic Analysis: Peak Plasma Drug Concentration (Cmax) [Time Frame: Predose (0 hours) and 0.5, 1, 2, 4, 8, 12, 13 (vildagliptin 50 mg BID only), 14 (vildagliptin 50 mg BID only), 16, 20, 24, 36, 48 and 96 hours after the morning dose on Day 5]

Pharmacokinetic Analysis: Time to the Peak Plasma Drug Concentration (Tmax) [Time Frame: Predose (0 hours) and 0.5, 1, 2, 4, 8, 12, 13 (vildagliptin 50 mg BID only), 14 (vildagliptin 50 mg BID only), 16, 20, 24, 36, 48 and 96 hours after the morning dose on Day 5]

Secondary ID(s)

0431-142

2011-005567-25

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 22/01/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01582308