- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02738879
Randomized Sitagliptin Withdrawal Study (MK-0431-845)
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of the Continuation of Sitagliptin Compared With the Withdrawal of Sitagliptin During Initiation and Titration of Insulin Glargine (LANTUS®) in Subjects With Type 2 Diabetes Mellitus
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Have T2DM based on American Diabetes Association guidelines
Be on one of the following treatment regimens:
Stable dose of sitagliptin (100 mg/day) and metformin IR or XR (metformin) (≥1500 mg/day) either co-administered or as a fixed dose combination (FDC) for ≥12 weeks with A1C between 7.5% and 11.0%, inclusive.
OR
Stable dose of metformin (≥1500 mg/day) and another dipeptidyl peptidase-4 (DPP-4) inhibitor (at maximum labeled dose, other than sitagliptin, either co-administered or as a FDC, for ≥12 weeks with A1C between 7.5% and 11.0%, inclusive.
OR
Stable dose of sitagliptin (100 mg/day) and metformin (≥1500 mg/day) either co administered or as a FDC, and a sulfonylurea for ≥12 weeks OR stable dose of metformin (≥1500 mg/day) and a sulfonylurea administered as a FDC and sitagliptin (100 mg/day) with A1C between 7.0% and 10.0%, inclusive.
OR
- Stable dose of metformin (≥1500 mg/day) and another DPP-4 inhibitor (at maximum labeled dose), other than sitagliptin, either co-administered or as a FDC, and a sulfonylurea for ≥12 weeks OR stable dose of metformin (≥1500 mg/day) and a sulfonylurea administered as a FDC and another DPP-4 inhibitor other than sitagliptin with A1C between 7.0% and 10.0%, inclusive OR
- Stable dose of metformin (≥1500 mg/day) and a sulfonylurea either co-administered or as a FDC for ≥12 weeks with A1C between 7.5% and 11.0%, inclusive.
Meet one of the following categories:
- The participant is a male
- The participant is a female who is not of reproductive potential
- The participant is a female who is of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by practicing abstinence from heterosexual activity OR use (or have her partner use) acceptable contraception during heterosexual activity
Exclusion Criteria:
- Has been treated with any anti-hyperglycemic agent (AHA) other than protocol-specified agents (i.e., other than metformin, DPP-4 inhibitor, or sulfonylurea agent) within the prior 12 weeks.
- Has a history of 2 or more episodes of hypoglycemia resulting in seizure, coma, or loss of consciousness, OR has had recurrent (≥3 times per week) episodes of hypoglycemia over the past 8 weeks.
- Has a history of type 1 diabetes mellitus (T1DM) or ketoacidosis, or has a history of latent autoimmune diabetes of adults (LADA), is assessed by the investigator as possibly having T1DM or LADA confirmed with a C-peptide <0.7 ng/mL (<0.23 nmol/L), or has a history of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, or post-organ transplant).
- Is assessed by the investigator to be not appropriate for, or does not agree to target, a fasting glucose of 72-100 mg/dL (4.0-5.6 mmol/L).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sitagliptin
Sitagliptin 100 mg, oral, once daily for 30 weeks
|
Sitagliptin 100 mg, oral, once daily for 30 weeks
Other Names:
At least 1500 mg/day, oral, twice daily for participants entering the study on immediate-release metformin + sitagliptin or a fixed dose combination (FDC).
At least 1500 mg/day, oral, once daily for participants entering the study on extended-release metformin + sitagliptin or a FDC.
Insulin glargine (LANTUS®) initiated at 10 units and titrated based on a treat-to-target algorithm to achieve fasting glucose levels of 72-100 mg/dL (4-5.6 mmol/L); administered once daily subcutaneously.
Other Names:
|
Placebo Comparator: Placebo
Placebo to sitagliptin, 100 mg, oral, once daily for 30 weeks
|
At least 1500 mg/day, oral, twice daily for participants entering the study on immediate-release metformin + sitagliptin or a fixed dose combination (FDC).
At least 1500 mg/day, oral, once daily for participants entering the study on extended-release metformin + sitagliptin or a FDC.
Insulin glargine (LANTUS®) initiated at 10 units and titrated based on a treat-to-target algorithm to achieve fasting glucose levels of 72-100 mg/dL (4-5.6 mmol/L); administered once daily subcutaneously.
Other Names:
Placebo to sitagliptin, 100 mg, oral, once daily for 30 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in A1C at Week 30
Time Frame: Baseline and Week 30
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time.
Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100.
Thus, this change from baseline reflects the Week 30 A1C minus the Week 0 A1C.
|
Baseline and Week 30
|
Event Rate of Documented Symptomatic Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
Time Frame: Up to 30 weeks
|
Documented symptomatic hypoglycemia is defined as an event during which typical symptoms of hypoglycemia are accompanied by a measured (e.g., by fingerstick) plasma glucose concentration ≤70 mg/dL (≤3.9 mmol/L).
The event rate was the total number of events divided by follow-up time (participant-years), including multiple events from the same participant.
|
Up to 30 weeks
|
Percentage of Participants Who Discontinued Study Drug Due to an AE
Time Frame: Up to 30 weeks
|
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
|
Up to 30 weeks
|
Percentage of Participants Who Experienced One or More Adverse Events (AEs)
Time Frame: Up to 32 weeks
|
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
|
Up to 32 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Events of Documented Symptomatic Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
Time Frame: Up to 30 weeks
|
Documented symptomatic hypoglycemia is defined as an event during which typical symptoms of hypoglycemia are accompanied by a measured (e.g., by fingerstick) plasma glucose concentration ≤70 mg/dL (≤3.9 mmol/L).
The incidence (number of participants with ≥1 event divided by number of participants) of documented symptomatic hypoglycemia was determined.
|
Up to 30 weeks
|
Change From Baseline in Total Daily Insulin Dose (Units) at Week 30
Time Frame: Baseline and Week 30
|
Change from baseline reflects the Week 30 total daily insulin dose minus the Week 0 total daily insulin dose.
The Week 0 total daily insulin dose was 0, by definition, because insulin was not administered at baseline.
|
Baseline and Week 30
|
Event Rate of Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
Time Frame: Up to 30 weeks
|
Documented hypoglycemia is defined by a measured (e.g., by fingerstick) plasma glucose concentration ≤70 mg/dL (≤3.9 mmol/L).
The event rate was the total number of events divided by follow-up time (participant-years), including multiple events from the same participant.
|
Up to 30 weeks
|
Event Rate of Documented Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
Time Frame: Up to 30 weeks
|
Documented hypoglycemia is defined by a measured (e.g., by fingerstick) plasma glucose concentration <56 mg/dL (≤3.1 mmol/L).
The event rate was the total number of events divided by follow-up time (participant-years), including multiple events from the same participant.
|
Up to 30 weeks
|
Percentage of Participants With Documented Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
Time Frame: Up to 30 weeks
|
Documented hypoglycemia is defined by a measured (e.g., by fingerstick) plasma glucose concentration <56 mg/dL (≤3.1 mmol/L).
|
Up to 30 weeks
|
Percentage of Participants With A1C Goal <7.0% (<53 mmol/Mol) at Week 30
Time Frame: Week 30
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time.
Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100.
|
Week 30
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Time Frame: Baseline and Week 30
|
Blood glucose was measured on a fasting basis.
Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at Week 0).
|
Baseline and Week 30
|
Event Rate of Documented Symptomatic Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
Time Frame: Up to 30 weeks
|
Documented symptomatic hypoglycemia is defined as an event during which typical symptoms of hypoglycemia are accompanied by a measured (e.g., by fingerstick) plasma glucose concentration <56 mg/dL (≤3.1 mmol/L).
The event rate was the total number of events divided by follow-up time (participant-years), including multiple events from the same participant.
|
Up to 30 weeks
|
Percentage of Participants With Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
Time Frame: Up to 30 weeks
|
Documented hypoglycemia is defined by a measured (e.g., by fingerstick) plasma glucose concentration ≤70 mg/dL (≤3.9 mmol/L).
|
Up to 30 weeks
|
Percentage of Participants With Documented Symptomatic Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
Time Frame: Up to 30 weeks
|
Documented symptomatic hypoglycemia is defined as an event during which typical symptoms of hypoglycemia are accompanied by a measured (e.g., by fingerstick) plasma glucose concentration <56 mg/dL (≤3.1 mmol/L).
|
Up to 30 weeks
|
Percentage of Participants With A1C Goal <7.0% (<53 mmol/Mol at Week 30 and No Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L) up to Week 30
Time Frame: Week 30
|
A1C is blood marker used to report average blood glucose levels over prolonged periods of time.
Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100.
|
Week 30
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Metformin
- Insulin Glargine
- Sitagliptin Phosphate
Other Study ID Numbers
- 0431-845
- 2015-004990-34 (EudraCT Number)
- MK-0431-845 (Other Identifier: Merck Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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