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)

NCT01590797 | Completed Phase 3 Results

• 1 other identifier: 0431-254
• Study Type: interventional
• Target: 467
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin

  Baseline and Week 24

• Number of Participants With One or More Adverse Events

  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.

  Up to Week 26

• Number of Participants Discontinuing Study Medication Due to an AE

  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 Week 24

Secondary Outcomes (2)

• Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin

  Baseline and Week 24

• Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin

  Baseline and Week 24

Study Arms (2)

Sitagliptin

EXPERIMENTAL

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; Biological: Insulin; Drug: Metformin

Placebo

PLACEBO COMPARATOR

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; Biological: Insulin; Drug: Metformin

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg once daily for 24 weeks

Also known as: Januvia®, MK-0431

Sitagliptin

Placebo DRUG

Matching placebo once daily for 24 weeks

Placebo

Insulin BIOLOGICAL

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.

Placebo; Sitagliptin

Metformin DRUG

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; Sitagliptin

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Shankar RR, Bao Y, Han P, Hu J, Ma J, Peng Y, Wu F, Xu L, Engel SS, Jia W. Sitagliptin added to stable insulin therapy with or without metformin in Chinese patients with type 2 diabetes. J Diabetes Investig. 2017 May;8(3):321-329. doi: 10.1111/jdi.12585. Epub 2016 Dec 9.

  PMID: 27740719 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Insulin; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2012
• First Posted: May 3, 2012
• Study Start: July 10, 2012
• Primary Completion: June 11, 2014
• Study Completion: June 25, 2014
• Last Updated: August 17, 2018
• Results First Posted: January 27, 2015

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share