Skip to main content
OpenTrials
Completed

NCT Number: NCT01582308

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sitagliptin 100 mg

Drug

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.

Other names: Januvia™

Saxagliptin 5 mg

Drug

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.

Other names: Onglyza™

Vildagliptin 50 mg

Drug

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.

Other names: Galvus™

Vildagliptin 50 mg bid

Drug

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.

Other names: Galvus™

Placebo

Drug

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.

Primary outcomes

  1. Percent Inhibition of Dipeptidyl Peptidase IV (DPP-4) Activity at Trough

    Time frame: 24 hours following the final morning dose on Day 5

    Percent inhibition of DPP-4 activity at 24 hours after the Day 5 morning dose (i.e., at trough) was determined by analysis of blood samples collected from the study participants.

Secondary outcomes

  1. 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

    AUC 0-24hr is the area under the plasma drug concentration-time curve calculated for the 24 hour interval after the Day 5 morning dose.

  2. 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

    AUC 0-12hr is the area under the plasma drug concentration-time curve calculated for the 12 hour interval after the Day 5 morning dose for the vildagliptin 50 mg BID dose only.

  3. 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

    Measurement of the peak plasma drug concentration following the Day 5 morning dose.

  4. 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

    Measurement of the time to the peak plasma drug concentration following the Day 5 morning dose.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Study to Assess and Compare the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Patients With Type 2 Diabetes Mellitus

Important dates

Study start
2012
Primary completion
2012
Study completion
2012
First posted
Apr 20, 2012
Registry last updated
May 30, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.