Randomized Sitagliptin Withdrawal Study

• Register: EUCTR
• Last refreshed on: 26 March 2018
• Main ID: EUCTR2015-004990-34-LV
• Date of registration: 20/04/2016
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
• Public title: Randomized Sitagliptin Withdrawal Study
• Scientific 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 - Randomized Sitagliptin Withdrawal Study
• Date of first enrolment: 06/06/2016
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004990-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, Denmark, Estonia, France, Germany, Hungary, Israel, Korea, Republic of, Latvia, Philippines, Poland, Puerto Rico, Romania, Russian Federation, Spain, Turkey, United States

Contacts

• Name: Global Clinical Trial operation
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc

• Name: Global Clinical Trial operation
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc

Key inclusion & exclusion criteria

Inclusion criteria:
In order to be eligible for participation in this trial, the subject must: (1) have T2DM and be > or = 18 years of age on the day of signing ICF; (2) be on one of the following treatment regimens: (a) stable dose of sitagliptin (100 mg/day) and metformin IR or XR (> or = 1500 mg/day) either co-administered or as a FDC for > or = 12 weeks with A1C between 7.5% and 11.0%, inclusive; (b) stable dose of metformin IR or XR (> or = 1500 mg/day) and another DPP-4 inhibitor (at maximum labeled dose), other than sitagliptin, either co-administered or as a FDC, for > or = 12 weeks with A1C between 7.5% and 11.0%, inclusive; (c) stable dose of sitagliptin (100 mg/day) and metformin IR or XR (> or = 1500 mg/day) either co-administered or as a FDC, and a sulfonylurea for > or = 12 weeks OR stable dose of metformin IR or XR (> or = 1500 mg/day) and a sulfonylurea administered as a FDC and sitagliptin (100 mg/day) with A1C between 7.0% and 10.0%, inclusive; (d) stable dose of metformin IR or XR (> or = 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 > or = 12 weeks OR stable dose of metformin IR or XR (> or = 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; (e) stable dose of metformin IR or XR (> or = 1500 mg/day) and a sulfonylurea either co-administered or as a FDC for > or = 12 weeks with A1C between 7.5% and 11.0% (> or = 58 mmol/mol and < or = 97 mmol/mol), inclusive. (3) At Visit 3, have an A1C of 7.5% to 11.0%.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 560
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion criteria:
The subject must be excluded from participating in the trial if the subject: (1) has been treated with any AHA other than protocol-specified agents (i.e., other than metformin, DPP-4 inhibitor, or sulfonylurea agent) within the prior 12 weeks; (2) has a history of 2 or more episodes of hypoglycemia resulting in seizure, coma, or loss of consciousness, OR subject has had recurrent (> or = 3 times per week) episodes of hypoglycemia over the past 8 weeks; (3) has a history of type 1 diabetes mellitus (T1DM) or ketoacidosis, or has a history of latent autoimmune diabetes of adults (LADA), or subject 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; (4) has a history of intolerance or hypersensitivity to sitagliptin, insulin, or metformin or any contraindication to sitagliptin, insulin, or metformin based upon the label of the country of the investigational site; (5) is currently participating, or has participated, in a study in which the subject received an investigational compound or used an investigational device within the prior 12 weeks of signing informed consent or is not willing to refrain from participating in another study; (6) is currently on or likely to require treatment with a prohibited medication (see Section 5.5.2 of protocol). Example: is on, or likely to require treatment with more than 14 consecutive days or repeated courses of pharmacologic doses of corticosteroids; (8) is pregnant or breast-feeding; (9) has an exclusionary laboratory value as listed in the protocol; (10) At Visit 4, has a site fasting fingerstick glucose of <130 mg/dL (7.2 mmol/L) or >270 mg/dL (15.0 mmol/L).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus (T2DM)

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Januvia
Product Code: MK-0431
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sitagliptin Phosphate
Current Sponsor code: MK-0431
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): (1) Change from baseline in A1C at Week 30; (2) Event rate of documented symptomatic hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L) over 30 weeks.

Secondary Objective: In subjects with T2DM with inadequate glycemic control on metformin and sitagliptin, who initiate and titrate insulin glargine (LANTUS®), to assess the effect of continuing sitagliptin relative to withdrawing sitagliptin on: 1) the incidence of the following over 30 weeks: a) documented symptomatic hypoglycemia with blood glucose (BG) < or =70 mg/dL; b) documented hypoglycemia with BG < or =70 mg/dL; c) documented symptomatic hypoglycemia with BG <56 mg/dL; d) documented hypoglycemia with BG <56 mg/dL; 2) the event rate of the following over 30 weeks: a) documented symptomatic hypoglycemia with BG <56 mg/dL; b) documented hypoglycemia with BG < or =70 mg/dL ; c) documented hypoglycemia with BG <56 mg/dL; 3) the daily dose of insulin after 30 weeks; 4) the proportion of subjects with A1C <7.0% after 30 weeks; 5) the proportion of subjects with A1C <7.0% after 30 weeks without any event of documented hypoglycemia with BG < or =70 mg/dL ; 6) fasting plasma glucose after 30 weeks.

Main Objective: In subjects with T2DM with inadequate glycemic control on metformin and sitagliptin, who initiate and titrate insulin glargine (LANTUS®), to assess the effect of continuing sitagliptin relative to withdrawing sitagliptin on: (1) HbA1c (A1C) after 30 weeks; (2) the event rate of documented symptomatic hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L) over 30 weeks; (3) general safety and tolerability over 30 weeks.

Timepoint(s) of evaluation of this end point: 30 weeks

Secondary Outcome(s)

Secondary end point(s): 1) Event rate of documented symptomatic hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L) over 30 weeks; (2) Incidence of each of the following over 30 weeks: (a) documented symptomatic hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L); (b) documented hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L); (c) documented symptomatic hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L); (d) documented hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L); (3) Change from baseline in total daily insulin dose at Week 30; (4) Event rate of each of the following over 30 weeks: (a) documented hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L); (b) documented hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L); (5) Proportion of subjects at A1C goal <7.0% (<53 mmol/mol) at Week 30; (6) Proportion of subjects at A1C goal <7.0% (<53 mmol/mol) at Week 30 with no documented hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L); (7) Change from baseline in FPG at Week 30.

Timepoint(s) of evaluation of this end point: 30 weeks

Secondary ID(s)

MK-0431-845

2015-004990-34-EE

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.