Clinical trial NCT02738879: Randomized Sitagliptin Withdrawal Study (MK-0431-845)
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of the Continuation of Sitagliptin Compared With the Withdrawal of Sitagliptin During Initiation and Titration of Insulin Glargine (LANTUS®) in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 746
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Change From Baseline in A1C at Week 30
timeFrame: Baseline and Week 30
measure: Event Rate of Documented Symptomatic Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
timeFrame: Up to 30 weeks
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 30 weeks
measure: Percentage of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to 32 weeks
Secondary outcomes:
measure: Percentage of Participants With Events of Documented Symptomatic Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
timeFrame: Up to 30 weeks
measure: Change From Baseline in Total Daily Insulin Dose (Units) at Week 30
timeFrame: Baseline and Week 30
measure: Event Rate of Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
timeFrame: Up to 30 weeks
measure: Event Rate of Documented Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
timeFrame: Up to 30 weeks
measure: Percentage of Participants With Documented Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
timeFrame: Up to 30 weeks
measure: Percentage of Participants With A1C Goal <7.0% (<53 mmol/Mol) at Week 30
timeFrame: Week 30
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
timeFrame: Baseline and Week 30
measure: Event Rate of Documented Symptomatic Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
timeFrame: Up to 30 weeks
measure: Percentage of Participants With Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L)
timeFrame: Up to 30 weeks
measure: Percentage of Participants With Documented Symptomatic Hypoglycemia With Blood Glucose <56 mg/dL (≤3.1 mmol/L)
timeFrame: Up to 30 weeks
measure: Percentage of Participants With A1C Goal <7.0% (<53 mmol/Mol at Week 30 and No Documented Hypoglycemia With Blood Glucose ≤70 mg/dL (≤3.9 mmol/L) up to Week 30
timeFrame: Week 30
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.