A Study Comparing the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-142)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin 100 mg; Saxagliptin 5 mg; Vildagliptin 50 mg; Vildagliptin 50 mg BID; Placebo
Intervention description: Sitagliptin 100 mg: one sitagliptin 100 mg tablet once daily in the morning following a fast of at least approximately 8 hours on Days 1 through 5 in one out of five treatment periods.; Saxagliptin 5 mg: one saxagliptin 5 mg tablet once daily in the morning following a fast of at least approximately 8 hours on Days 1 through 5 in one out of five treatment periods.; Vildagliptin 50 mg: one vildagliptin 50 mg tablet once daily in the morning following a fast of at least approximately 8 hours on Days 1 through 5 in one out of five treatment periods.; Vildagliptin 50 mg BID: one vildagliptin 50 mg tablet BID (twice daily), once in the morning following a fast of at least approximately 8 hours and once in the evening on Days 1 through 5 in one out of five treatment periods.; Placebo: one placebo for sitagliptin tablet once daily in the morning following a fast of at least approximately 8 hours on Days 1 through 5 in one out of five treatment periods.
Intervention MeSH terms: Sitagliptin Phosphate; Vildagliptin; Saxagliptin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      A five-period crossover study to assess and compare the trough dipeptidyl peptidase IV
      (DPP-4) inhibition at 24-hours following the final morning dose for sitagliptin, saxagliptin
      and vildagliptin after 5 days of once daily dosing and vildagliptin after 5 days of twice
      daily dosing in participants with T2DM. The primary hypothesis is that following multiple
      daily dose administration to achieve steady-state drug concentrations, 100-mg sitagliptin
      will demonstrate greater DPP-4 inhibition at 24-hours after the final dose compared to 5-mg
      saxagliptin and 50-mg vildagliptin (once daily administration) in participants with T2DM.
      Each participant will receive all 5 treatments in randomized order. There will be a washout
      interval of at least 10 days between the last dose of study drug in one period and the first
      dose of study drug in the following period.
    

Eligibility 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