Randomized Sitagliptin Withdrawal Study (MK-0431-845)

NCT02738879 | Completed Phase 3 Results

• 3 other identifiers: 0431-8452015-004990-34MK-0431-845
• Study Type: interventional
• Target: 746
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a trial of continuing sitagliptin versus withdrawing sitagliptin in participants with Type 2 diabetes mellitus (T2DM) and inadequate glycemic control who initiate and titrate insulin glargine (LANTUS®) based on a treat-to-target algorithm to achieve fasting glucose levels of 72-100 mg/dL (4-5.6 mmol/L). A primary hypothesis of this trial is that after 30 weeks, continuing sitagliptin results in a greater reduction of hemoglobin A1C (A1C) relative to withdrawing sitagliptin.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in A1C at 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)

  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

  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)

  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 Outcomes (11)

• Percentage of Participants With Events of Documented Symptomatic Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)

  Up to 30 weeks

• Change From Baseline in Total Daily Insulin Dose (Units) at Week 30

  Baseline and Week 30

• Event Rate of Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)

  Up to 30 weeks

• Event Rate of Documented Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)

  Up to 30 weeks

• Percentage of Participants With Documented Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)

  Up to 30 weeks

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Sitagliptin 100 mg, oral, once daily for 30 weeks

Drug: Sitagliptin; Drug: Metformin; Drug: Metformin XR; Drug: Insulin glargine

Placebo

PLACEBO COMPARATOR

Placebo to sitagliptin, 100 mg, oral, once daily for 30 weeks

Drug: Placebo to sitagliptin; Drug: Metformin; Drug: Metformin XR; Drug: Insulin glargine

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg, oral, once daily for 30 weeks

Also known as: Januvia®

Sitagliptin

Placebo to sitagliptin DRUG

Placebo to sitagliptin, 100 mg, oral, once daily for 30 weeks

Placebo

Metformin DRUG

At least 1500 mg/day, oral, twice daily for participants entering the study on immediate-release metformin + sitagliptin or a fixed dose combination (FDC).

Placebo; Sitagliptin

Metformin XR DRUG

At least 1500 mg/day, oral, once daily for participants entering the study on extended-release metformin + sitagliptin or a FDC.

Placebo; Sitagliptin

Insulin glargine DRUG

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.

Also known as: LANTUS®)

Placebo; Sitagliptin

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Roussel R, Duran-Garcia S, Zhang Y, Shah S, Darmiento C, Shankar RR, Golm GT, Lam RLH, O'Neill EA, Gantz I, Kaufman KD, Engel SS. Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT-I Study. Diabetes Obes Metab. 2019 Apr;21(4):781-790. doi: 10.1111/dom.13574. Epub 2018 Dec 9.

  PMID: 30393950 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Metformin; Insulin Glargine

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; Biguanides; Guanidines; Amidines; Organic Chemicals; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Clinical Trials Disclosure
• 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: April 11, 2016
• First Posted: April 14, 2016
• Study Start: May 9, 2016
• Primary Completion: January 22, 2018
• Study Completion: January 30, 2018
• Last Updated: February 25, 2019
• Results First Posted: February 25, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share