A Phase 3 study in Patients with Type 2 Diabetes Mellitus

• Conditions: Type 2 Diabetes Mellitus; MedDRA version: 18.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2012-002414-39-NL
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-04
• Last Update Posted: 2 May 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 4000

Inclusion Criteria

1. Having T2DM and is =40 years of age.
2. Subject is on one of the following diabetes treatment regimens that is stable for at least 12 weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C range for that treatment regimen:
- An A1C =6.5 and =10.0% (=48 mmol/mol and =86 mmol/mol) on
diet and exercise alone (not on an AHA for =12 weeks)
OR
monotherapy with metformin (MF); pioglitazone (PIO); an alpha-glucosidase inhibitor (AGI); or an SGLT2 inhibitor (SGLT2i)
OR
dual combination therapy with MF, PIO, AGI or SGLT2i
OR
- An A1C =7.0% and =10.0% (=53 mmol/mol and =86 mmol/mol) on
monotherapy with a sulfonylurea or meglitinide
OR
dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i
OR
- An A1C =7.0% and =10.0% (=53 mmol/mol and =86 mmol/mol) on one of the following insulin regimens (with or without metformin)
basal insulin (e.g., insulin glargine, insulin detemir, NPH insulin, degludec)
prandial insulin (e.g., regular, aspart, lispro, glulisine)
basal/prandial insulin regimen consisting of multiple dose insulin injections of basal and prandial insulin or the use of pre-mixed insulin (e.g., Novolog 70/30®, Novolin 70/30®, Humalog 75/25®, or Humulin 70/30®)
Note: A stable insulin regimen is defined as no change in the insulin regimen (i.e. type[s] of insulin) and =10% change in the total daily dose of insulin. For example, if the total daily dose of insulin is 50 U/day, doses of 45-55 U/day would be considered as stable.
3. Having following preexisting vascular disease:
(a) History of a major clinical manifestation of coronary artery disease (i.e., myocardial infarction, surgical or percutaneous [balloon and/or stent] coronary revascularization procedure, or coronary angiography showing at least one stenosis =50% in a major epicardial artery or branch vessel);
(b)Ischemic cerebrovascular disease, including:
- History of ischemic stroke
- History of carotid arterial disease as documented by =50% stenosis documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography, with or without symptoms of neurologic deficit.
(c) Atherosclerotic peripheral arterial disease, as documented by objective - amputation due to vascular disease, current symptoms of intermittent claudication confirmed by an ankle-brachial pressure index of less than 0.9 or a toe-brachial pressure index less than 0.7 or history of surgical or percutaneous revascularization procedure.
4.Meets one of the following criteria:
a. Subject is a male
b. Subject is a female not of reproductive potential defined as one who has either:
(1) reached natural menopause (defined as =12 months of spontaneous amenorrhea in women >45 years of age, or =6 months of spontaneous amenorrhea with serum follicular stimulating hormone [FSH] levels in the postmenopausal range as determined by the laboratory), or
(2)had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to screening
c. Subject is a female of reproductive potential and:
1. agrees to remain abstinent from heterosexual activity (if this form of birth control is accepted by local regulatory agencies and ethics review committees as the sole method of birth control) or
2. agrees to use (or have their partner use) acceptable contraception to prevent pregnancy within the projected duration of the trial and for 21 days after the last dose of blinded study medi

Exclusion Criteria

1. History of type 1 diabetes mellitus or a history of ketoacidosis or possibly having type 1 diabetes
2. Beeing treated with rosiglitazone, a DPP-4 inhibitor or a GLP-1 receptor agonist within the prior 12 weeks of Visit 1/Screening or previously treated with MK-3102.
3. Having a history of hypersensitivity to a DPP-4 inhibitor
4. Participation in trial with investigational compound prior 12 weeks of signing the informed consent or is not willing to refrain from participating in another trial.
5. Subject is on a weight loss program and is not in the maintenance phase; has been on a weight loss medication in the past 6 months; or has undergone bariatric surgery within 12 months prior to signing the informed consent.
6. Surgical procedure within 4 weeks prior to signing informed consent or has planned major surgery during the trial.
7. Treatment for =14 consecutive days or repeated courses of pharmacologic doses of corticosteroids
8. Treatement for hyperthyroidism or thyroid replacement therapy and has not been on a stable dose for at least 6 weeks.
9. Medical history of active liver disease
10. Human immunodeficiency virus (HIV) as assessed by medical history.
11. Worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months.
12. Poorly-controlled hypertension
13. History of malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
14. Clinically important hematological disorder
15. Exclusionary laboratory values
16. Positive urine pregnancy test.
17.Subject is pregnant or breast-feeding, or is expecting to conceive during the trial, including 21 days following the last dose of blinded study medication. OR is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 21 days following the last dose of blinded study medication.
18. Subject is,at the time of signing informed consent,a user of recreational or illicit drugs or has had a recent history of drug abuse.
19. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per
week, or engages in binge drinking.
20. History or current evidence of condition, therapy, lab abnormality or other circumstance that
•makes participation not in the subject’s best interest
•might interfere with subject´s participation for the full duration of the trial, or
•might confound the result of the trial.
21.Subject has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent, or intends to donate blood products within the projected duration of the trial OR received, or anticipated to receive blood products within 12 weeks of signing informed consent or within the projected duration of the trial.
22. Subject is unlikely to adhere to the trial procedures, keep appointments.
23.Symptomatic hyperglycemia that, in the investigator's opinion, requires immediate initiation, adjustment, or addition of AHA therapy or has a FPG consistently (i.e., measurement repeated and confirmed within 7 days) >260 mg/dL (14.4 mmol/L).
24.Clinically significant ECG abnormality which in the opinion of the investigator exposes the subject to risk by enrolling in the trial.
25.Poorly controlled hypertension defined as systolic blood pressure of =160 mm Hg or diastolic blood pressure of =90 mm Hg.
26.Subject is on lipid-lowering medication or thyroid

Study & Design

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