Study to assess the safety and efficacy of sitagliptin added to ongoing metformin therapy compared with the addition of placebo to ongoing metformin therapy for the treatment of T2DM in pediatric patients (10-17 years of age, inclusive) with inadequate glycemic control on metformin monotherapy.

Phase 1

• Conditions: Pediatric patients (10-17 years of age, inclusive) with type 2 diabetesmellitus (T2DM) with inadequate glycemic control on metformin monotherapy.; MedDRA version: 14.1Level: LLTClassification code 10049746Term: Insulin-requiring type II diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2011-002529-23-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-03-19
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Patients must meet all of the following criteria to participate in the study.
At Visit 1
1. Patient has T2DM as indicated by yes answers to all of the following:
a) Patient has diabetes diagnosed by American Diabetes Association (ADA) criteria
(laboratory determinations of fasting plasma glucose =126 mg/dL [6.99 mmol/L],
or random plasma glucose =200 mg/dL [11.11 mmol/L], or two-hour oral glucose
tolerance test (OGTT) plasma glucose =200 mg/dL [11.11 mmol/L], and
confirmed per ADA guidelines) documented in medical record.
b) Patient is assessed as having a clinical profile consistent with T2DM (e.g., based
upon body weight, family history, presentation).
c) Patient has BMI SD Score =1.04 (=85th percentile) at screening (or patient has a
history of being overweight or obese at time of diagnosis of T2DM). See
Appendix 6.7.
d) Patient has
i) diabetes for =2 years
or
ii) diabetes for <2 years and a fasting C-peptide value >0.6 ng/mL at Screening
Visit/Visit 1.
2. Patient has not received treatment with insulin for at least 6 months prior to the
Screening Visit/Visit 1.
3. Patient has an A1C =7.0% and =10.0% on metformin, =1500 mg/day, for =12 weeks.
4. Patient is 10 and 17 years of age on day of signing informed consent with
randomization to occur prior to the patient’s 18th birthday.
5. Patient is either a male, or patient is a female who is unlikely to conceive as indicated
by at least one es response to the following which will remain consistent for the
projected duration of the study and for 14 days after the last dose of study medication:
a) Patient is a non-sterilized female who is currently not sexually active and agrees
to follow statement c if heterosexual activity is initiated
or
b) Patient agrees to abstain from heterosexual activity
or
c) Patient agrees to use an adequate method of contraception.
6. Parent/guardian understands the study procedures, alternative treatments available
and risks involved with the study, and voluntarily agrees to the patient’s participation
by giving informed written consent, and the patient has an age-appropriate
understanding of the same to give informed written assent. In addition, the parent/
guardian may also consent to have the child participate in Future Biomedical
Research (FBR) by signing a separate consent.
7. Patient and a family member or adult closely involved in the patient’s daily activities
(in the opinion of the investigator) will participate in the patient’s treatment and study
protocol (i.e., available for telephone calls, study visits and administration of study
medication as needed).
At Visit 3/Day 1/Randomization
8. Patient has =80% compliance with placebo treatment during the single-blind run-in as
measured by site-performed pill count.
Are the trial subjects under 18? yes
Number of subjects for this age range: 240
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Individuals are excluded from participation in the study if they meet any of the following
criteria.
At Visit 1
Glucose Metabolism and Therapy Criteria
1. Patient has known type 1 diabetes mellitus or documented evidence of positive
diabetes auto-antibodies (if performed when patient was diagnosed with diabetes).
2. Patient has known monogenic diabetes, secondary diabetes, or a genetic syndrome or
disorder known to affect glucose tolerance other than diabetes.
3. Patient has symptomatic hyperglycemia and/or moderate to large ketonuria requiring
immediate initiation of another antihyperglycemic agent.
Specific Treatments
4. Patient has previously taken a DPP-4 inhibitor (such as sitagliptin, vildagliptin,
alogliptin, or saxagliptin) or GLP-1 receptor agonist (such as exenatide or liraglutide).
5. Patient has initiated chronic treatment with a medication known to cause:
a. weight gain within 30 days of Visit 1
or
b. weight loss (such as orlistat) or increase blood glucose within 8 weeks of Visit 1.
6. Patient is currently participating in or has participated in another study with an
investigational compound or device within the prior 12 weeks of signing the informed
consent (including patients who have participated in single-dose studies with these
agents) and does not agree to refrain from participating in any other study while
participating in this study.
7. Patient is on or likely to require treatment with =14 consecutive days or repeated
courses of pharmacologic doses of corticosteroids.
8. Patient has undergone a surgical procedure within the prior 4 weeks or has major
surgery planned during the study.
9. Patient has a history of congenital heart disease or cardiovascular disease other than
hypertension.
10. Patient has a Visit 1 systolic or diastolic blood pressure of =95th percentile for age,
height percentile and gender (see Appendix 6.2 and 6.3) and is not considered likely
to have values <95th percentile for age, height percentile and gender by Visit 3/Day 1
with appropriate antihypertensive therapy.
11. Patient has a medical history of active liver disease (other than non-alcoholic hepatic
steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or
symptomatic gallbladder disease.
12. Patient has active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).
13. Patient has chronic myopathy, mitochondrial disorder or a progressive neurological or
neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).
14. Patient has human immunodeficiency virus (HIV) as assessed by medical history.
15. Patient has a clinically significant hematological disorder (such as aplastic anemia,
thrombocytopenia, myeloproliferative or myelodysplastic syndrome).
16. Patient is under treatment for hyperthyroidism.
17. Patient exhibits abnormal growth patterns or is being treated with growth hormone.
18. Patient has a history of malignancy or clinically important hematologic disorder.
19. Patient has a history of idiopathic acute pancreatitis or chronic pancreatitis.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified