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

Purpose

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 of this study 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. 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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Sitagliptin Drug: Saxagliptin Drug: Vildagliptin Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Study to Assess and Compare the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Saxagliptin Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Percent inhibition of dipeptidyl peptidase IV (DPP-4) activity at trough [ Time Frame: 24 hours following the final morning dose on day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetic analysis: area under the curve (0-t) [ Time Frame: Day 5 dose through 96 hours post-dose Day 5 ] [ Designated as safety issue: No ]
Pharmacokinetic analysis: maximum concentration (Cmax) [ Time Frame: Day 5 dose through 96 hours post-dose Day 5 ] [ Designated as safety issue: No ]
Pharmacokinetic analysis: time to maximum concentration (Tmax) [ Time Frame: Day 5 dose through 96 hours post-dose Day 5 ] [ Designated as safety issue: No ]

Enrollment:	22
Study Start Date:	June 2012
Study Completion Date:	December 2012
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment Sequence 1 Sitagliptin 100 mg followed by saxagliptin 5 mg followed by vildagliptin 100 mg followed by placebo followed by vildagliptin 50 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 2 Saxagliptin 5 mg followed by vildagliptin 50 mg followed by placebo followed by sitagliptin 100 mg followed by vildagliptin 100 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 3 Vildagliptin 50 mg followed by vildagliptin 100 mg followed by sitagliptin 100 mg followed by saxagliptin 5 mg followed by placebo	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 4 Vildagliptin 100 mg followed by placebo followed by saxagliptin 5 mg followed by vildagliptin 50 mg followed by sitagliptin 100 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 5 Placebo followed by sitagliptin 100 mg followed by vildagliptin 50 mg followed by vildagliptin 100 mg followed by saxagliptin 5 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 6 Sitagliptin 100 mg followed by vildagliptin 50 mg followed by saxagliptin 5 mg followed by placebo followed by vildagliptin 100 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 7 Saxagliptin 5 mg followed by vildagliptin 100 mg followed by vildagliptin 50 mg followed by sitagliptin 100 mg followed by placebo	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 8 Vildagliptin 50 mg followed by placebo followed by vildagliptin 100 mg followed by saxagliptin 5 mg followed by sitagliptin 100 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 9 Vildagliptin 100 mg followed by sitagliptin 100 mg followed by placebo followed by vildagliptin 50 mg followed by saxagliptin 5 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.
Experimental: Treatment Sequence 10 Placebo followed by saxagliptin 5 mg followed by sitagliptin 100 mg followed by vildagliptin 100 mg followed by vildagliptin 50 mg	Drug: Sitagliptin 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 Name: Januvia™ Drug: Saxagliptin 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 Name: Onglyza™ Drug: Vildagliptin 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 100 mg: one vildagliptin 50 mg tablet 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 Name: Galvus™ Drug: Placebo 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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
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%
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 approximate the last 6 months
is willing to follow the American Heart Association weight maintaining 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 patient 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

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01582308 History of Changes
Other Study ID Numbers:	0431-142
Study First Received:	April 19, 2012
Last Updated:	January 4, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vildagliptin
Sitagliptin
Saxagliptin

Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2013