A Study of the Safety and Efficacy of Sitagliptin Addition During Metformin Up-titration (MK-0431-848)

NCT02791490 | Completed Phase 3 Results

• 3 other identifiers: 0431-848MK-0431-8482015-004224-59
• Study Type: interventional
• Target: 458
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial is designed to evaluate, in adult participants with Type 2 diabetes mellitus (T2DM) and inadequate glycemic control on sub-maximal metformin mono-therapy (1000 mg/day), the effect of up-titration of metformin plus the addition of sitagliptin compared to up-titration of metformin alone on glycemic control. The primary hypothesis of this study is that up-titration of metformin to 2000 mg/day (1000 mg/twice a day) plus the addition of sitagliptin 100 mg/day provides greater reduction in hemoglobin A1C (A1C) compared to metformin up-titration alone. Another primary objective of this study is to evaluate the safety and tolerability of this treatment.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Hemoglobin A1C at Week 20

  Hemoglobin A1C is a 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. The change from baseline represents the Week 20 A1C value minus the Week 0 (baseline) A1C value.

  Baseline and Week 20

• Percentage of Participants Who Experienced at Least One Adverse Event (AE)

  An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

  Up to 22 weeks

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

  An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

  Up to 20 weeks

Secondary Outcomes (4)

• Percentage of Participants With Hemoglobin A1C <7% at Week 20

  Week 20

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20

  Baseline and Week 20

• Percentage of Participants With Hemoglobin A1C ≥8.5% at Baseline That Attained A1C Goal of <7% at Week 20

  Baseline and Week 20

• Percentage of Participants Receiving Glycemic Rescue Therapy

  Up to 20 weeks

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Participants will receive sitagliptin 100 mg once daily for 20 weeks. They will also receive immediate-release metformin (Met-IR), which will be titrated from a baseline dose of 1000 mg/day (500 mg/twice a day \[b.i.d.\]) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants will also receive glycemic rescue therapy as needed.

Drug: Sitagliptin; Drug: Metformin IR

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching sitagliptin once daily for 20 weeks. They will also receive Met-IR, which will be titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants will also receive glycemic rescue therapy as needed.

Drug: Placebo; Drug: Metformin IR

Interventions

Sitagliptin DRUG

Oral tablet, 100 mg, once daily at approximately the same time each day

Also known as: JANUVIA®, TESAVEL®, XELEVIA®, RISTABEN®

Sitagliptin

Placebo DRUG

Oral tablet, once daily at approximately the same time each day

Placebo

Metformin IR DRUG

All participants will take Met-IR as background medication. Initially, they will take 1 x 500 mg tablet Met-IR b.i.d. (1000 mg/day). After randomization, all participants will be titrated to 2 x 500 mg tablets of Met-IR b.i.d. (2000 mg/day).

Placebo; Sitagliptin

Eligibility Criteria

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

You may qualify if:

• Male or female participants with T2DM in accordance with American Diabetes Association (ADA) guidelines
• Meet one of the following criteria:
• Be on stable Met-IR monotherapy 1000 mg/day for ≥8 weeks with a Screening A1C ≥7.5% and ≤11.0%.
• Be on stable Met-XR monotherapy 1000 mg/day for ≥8 weeks with a Screening A1C ≥7.5% and ≤11.0%.
• Not on any anti-hyperglycemic agent (AHA) for ≥8 weeks (≥12 weeks if previously taking thiazolidinediones) with a Screening A1C ≥8.5% and ≤12.0%.
• Be on stable monotherapy with a sulfonylurea, a glinide, or an α-glucosidase inhibitor for ≥8 weeks with a Screening A1C ≥7.5% and ≤11.0%.
• A body mass index (BMI) ≥18.0 kg/m2.
• Is a male or a female not of reproductive potential (defined as one who is postmenopausal or has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to Screening visit). If participant is a female of reproductive potential, must agree to remain abstinent from heterosexual activity or agrees to use (or have her partner use) acceptable contraception to prevent pregnancy while receiving blinded study drug and for 14 days after the last dose of blinded study drug

You may not qualify if:

• Has a history of type 1 diabetes mellitus or a history of ketoacidosis or has a history of secondary causes of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant).
• A known hypersensitivity or intolerance to any DPP-4 inhibitor. A known hypersensitivity or intolerance to metformin, including participants who were previously unable to tolerate metformin at a dose \>1000 mg/day or who have evidence of intolerance to the dose of metformin they are currently taking.
• Has been treated with any of the following agents within 8 weeks (12 weeks for thiazolidinediones) of study participation:
• Insulin of any type (except for short-term use \[i.e., ≤7 days\] during concomitant illness or other stress)
• DPP-4 inhibitor
• Pioglitazone or rosiglitazone (thiazolidinediones)
• Glucagon-like peptide-1 receptor (GLP-1R) agonists
• Sodium glucose co-transporter 2 (SGLT2) inhibitors
• Bromocriptine (Cycloset™)
• Colesevelam (Welchol™)
• Any other AHA with the exception of protocol-approved agents
• Intends to initiate weight loss medication during the study period
• Has undergone bariatric surgery within 12 months of Screening visit
• Has started a weight loss medication or a medication associated with weight changes within the prior 12 weeks
• A history of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, NYHA functional class III-IV heart failure, or severe peripheral vascular disease (e.g., claudication with minimal activity, a nonhealing ischemic ulcer, or disease which is likely to require surgery or angioplasty) within 3 months of study participation

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Frias JP, Zimmer Z, Lam RLH, Amorin G, Ntabadde C, Iredale C, O'Neill EA, Engel SS, Kaufman KD, Makimura H, Crutchlow MF. Double-blind, randomized clinical trial assessing the efficacy and safety of early initiation of sitagliptin during metformin uptitration in the treatment of patients with type 2 diabetes: The CompoSIT-M study. Diabetes Obes Metab. 2019 May;21(5):1128-1135. doi: 10.1111/dom.13626. Epub 2019 Feb 17.

  PMID: 30609212 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate

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

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 6, 2016
• Study Start: June 16, 2016
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: February 28, 2019
• Results First Posted: February 28, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share