Randomized Sitagliptin Withdrawal Study (MK-0431-845)

NCT ID: NCT02738879

Last Updated: 2019-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 746 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-09
• Study Completion Date: 2018-01-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sitagliptin

Sitagliptin 100 mg, oral, once daily for 30 weeks

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Sitagliptin 100 mg, oral, once daily for 30 weeks

Metformin

Intervention Type: 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).

Metformin XR

Intervention Type: DRUG

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

Insulin glargine

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo to sitagliptin

Intervention Type: DRUG

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

Metformin

Intervention Type: 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).

Metformin XR

Intervention Type: DRUG

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

Insulin glargine

Intervention Type: 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.

Interventions

Sitagliptin

Sitagliptin 100 mg, oral, once daily for 30 weeks

Intervention Type: DRUG

Placebo to sitagliptin

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

Intervention Type: DRUG

Metformin

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

Intervention Type: DRUG

Metformin XR

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

Intervention Type: DRUG

Insulin glargine

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.

Intervention Type: DRUG

Other Intervention Names

Januvia®; LANTUS®)

Eligibility Criteria

Inclusion Criteria

• Have T2DM based on American Diabetes Association guidelines
• Be on one of the following treatment regimens:

1. 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

2. 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

3. 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

4. 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

5. 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:

1. The participant is a male

2. The participant is a female who is not of reproductive potential

3. 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 30393950 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-004990-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-0431-845

Identifier Type: OTHER

Identifier Source: secondary_id

0431-845

Identifier Type: -

Identifier Source: org_study_id