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A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Insulin With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-254)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01590797
First received: May 1, 2012
Last updated: January 16, 2015
Last verified: January 2015
  Purpose

A study to compare safety and efficacy of sitagliptin and placebo therapy when added to stable insulin alone or in combination with metformin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis of this study is that after 24 weeks, the addition of sitagliptin compared with placebo provides greater reduction in hemoglobin A1C (HbA1C) in T2DM participants on insulin alone or in combination with metformin.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Placebo
Biological: Insulin
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial in China to Study the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Therapy, Alone or in Combination With Metformin

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Number of Participants With One or More Adverse Events [ Time Frame: Up to Week 26 ] [ Designated as safety issue: Yes ]
    An adverse event (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.

  • Number of Participants Discontinuing Study Medication Due to an AE [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

Enrollment: 467
Study Start Date: July 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Drug: Sitagliptin
Sitagliptin 100 mg once daily for 24 weeks
Other Names:
  • Januvia®
  • MK-0431
Biological: Insulin
Participants can be on on pre-mixed (mixture of rapid- and long-acting insulin) or intermediate- or long-acting insulin at a dose of at least 12 U/day.
Drug: Metformin
At randomization, participants will be stratified according to their use of metformin (on or not on). All participants receiving metformin will be required to be on a daily dose of metformin at least 1500 mg per day.
Placebo Comparator: Placebo
Participants treated with placebo matching sitagliptin, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Drug: Placebo
Matching placebo once daily for 24 weeks
Biological: Insulin
Participants can be on on pre-mixed (mixture of rapid- and long-acting insulin) or intermediate- or long-acting insulin at a dose of at least 12 U/day.
Drug: Metformin
At randomization, participants will be stratified according to their use of metformin (on or not on). All participants receiving metformin will be required to be on a daily dose of metformin at least 1500 mg per day.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • has T2DM
  • is currently on a stable regimen of pre-mixed, intermediate-acting, or long-acting insulin at a dose of at least 12 U/day, either alone or in combination with metformin >=1500 mg/day for ≥ 10 weeks
  • has a Visit 1/Screening HbA1C between 7.5% and 11.0%
  • is a male, or a female who is highly unlikely to conceive during the study and for 14 days after the last dose of study medication

Exclusion Criteria:

  • has been treated with any antihyperglycemic therapies other than a protocol-required insulin (alone or with metformin) within the prior 12 weeks or has ever

been treated with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 mimetic or analogue

  • is currently on treatment with daily use (one or more injections per day) of

pre-prandial short-acting or rapid-acting insulin

  • has a history of 2 or more episodes of hypoglycemia resulting in seizure,

coma, or loss of consciousness, or has had recurrent episodes of hypoglycemia over the past 8 weeks

  • has a history of intolerance or hypersensitivity, or has any contraindication to sitagliptin, insulin, or metformin
  • is on a weight loss program and not in the maintenance phase, or has started a weight loss medication or has undergone bariatric surgery within 12 months
  • has undergone a surgical procedure within 4 weeks or has planned major surgery during the study
  • has a medical history of active liver disease
  • has had new or worsening signs or symptoms of coronary heart disease within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder
  • has a diagnosis of congestive heart failure with New York Heart Association Class III - IV cardiac status
  • has a systolic blood pressure ≥ 160 mmHg or a diastolic blood pressure ≥ 90 mmHg
  • has human immunodeficiency virus (HIV)
  • has severe peripheral vascular disease
  • is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
  • has a history of malignancy ≤ 5 years before the study, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
  • has a clinically important hematological disorder (such as aplastic anemia,

myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

  • is pregnant or breast feeding, or is expecting to conceive or donate eggs during the study, including 14 days after the last dose of study medication
  • is a user of recreational or illicit drugs or has had a recent history of drug abuse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590797

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01590797     History of Changes
Other Study ID Numbers: 0431-254
Study First Received: May 1, 2012
Results First Received: January 16, 2015
Last Updated: January 16, 2015
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Metformin
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on March 03, 2015