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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02791490
• Date of registration: 01/06/2016
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: A Study of the Safety and Efficacy of Sitagliptin Addition During Metformin Up-titration (MK-0431-848)
• Scientific title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin During Metformin Up-titration Compared With Metformin Up-titration Alone in Subjects With Type 2 Diabetes Mellitus
• Date of first enrolment: June 16, 2016
• Target sample size: 458
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02791490
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Canada, Czech Republic, Czechia, Guatemala, Mexico, Russian Federation, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme Corp.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female participants with T2DM in accordance with American Diabetes Association
(ADA) guidelines

- Meet one of the following criteria:

1. Be on stable Met-IR monotherapy 1000 mg/day for =8 weeks with a Screening A1C
=7.5% and =11.0%.

OR

2. Be on stable Met-XR monotherapy 1000 mg/day for =8 weeks with a Screening A1C
=7.5% and =11.0%.

OR

3. 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%.

OR

4. Be on stable monotherapy with a sulfonylurea, a glinide, or an a-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

Exclusion Criteria:

- 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:

1. Insulin of any type (except for short-term use [i.e., =7 days] during concomitant
illness or other stress)

2. DPP-4 inhibitor

3. Pioglitazone or rosiglitazone (thiazolidinediones)

4. Glucagon-like peptide-1 receptor (GLP-1R) agonists

5. Sodium glucose co-transporter 2 (SGLT2) inhibitors

6. Bromocriptine (Cycloset™)

7. Colesevelam (Welchol™)

8. 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

- A history of malignancy =5 years prior to study participation (i.e., the diagnosis
occurred, or any evidence of residual or recurrent disease occurred, within the past 5
years), except for adequately treated basal cell or squamous cell skin cancer, or in
situ cervical cancer. Note: A patient with any history of melanoma, leukemia,
lymphoma, or renal cell carcinoma is excluded.

- Has human immunodeficiency virus (HIV)

1. with AIDS related complications, or

2. has not been on a stable anti-retroviral regimen for >6 months, or

3. has progressive disease, or

4. using agents associated with glucose intolerance such as nucleoside reverse
transcriptase inhibitors (NRTIs) such as azidothymidine (AZT), didanosine (ddI),
and stavudine (d4T).

- Is on or likely to require treatment for =14 consecutive days or repeated courses of
pharmacologic doses of corticosteroids.

- Has undergone a major surgical procedure within 12 weeks prior to signing the informed
consent form (ICF) or has major surgery planned during the trial.

- Currently participating, or has participated, in a study in which the participant
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.

- Is pregnant or breast-feeding, has a positive urine pregnancy test, or is planning to
conceive or donate eggs during the study, including 14 days following the last dose of
blinded investigational product.

- A recent history of alcohol or drug abuse (within 3 years) or is a user of
recreational or illicit drugs at the time of screening.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus

Intervention(s)

Drug: Sitagliptin

Drug: Metformin IR

Drug: Placebo

Primary Outcome(s)

Percentage of Participants Who Experienced at Least One Adverse Event (AE) [Time Frame: Up to 22 weeks]

Change From Baseline in Hemoglobin A1C at Week 20 [Time Frame: Baseline and Week 20]

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event [Time Frame: Up to 20 weeks]

Secondary Outcome(s)

Percentage of Participants With Hemoglobin A1C =8.5% at Baseline That Attained A1C Goal of <7% at Week 20 [Time Frame: Baseline and Week 20]

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 [Time Frame: Baseline and Week 20]

Percentage of Participants Receiving Glycemic Rescue Therapy [Time Frame: Up to 20 weeks]

Percentage of Participants With Hemoglobin A1C <7% at Week 20 [Time Frame: Week 20]

Secondary ID(s)

0431-848

2015-004224-59

MK-0431-848

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/02/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02791490