Clinical trial NCT02059161: A Study of the Safety and Efficacy of MK-1293 Compared to Lantus™ in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003)
Official title: A Phase III Clinical Trial to Study the Safety and Efficacy of MK-1293 Compared to Lantus™ in Subjects With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-02-11
Enrollment: 508
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: The purpose of this study is to compare the safety and efficacy of MK-1293 to Lantus™ in participants with T1DM. The primary hypothesis is that after 24 weeks, the mean change in hemoglobin A1c (A1C) from baseline is non-inferior in participants treated with MK-1293 compared with participants treated with Lantus™.


Eligibility criteria: Inclusion Criteria:

* T1DM For at least 1 year
* is currently using or has been using prandial insulin for at least 4 weeks. Participants taking any type of basal insulin should require a total daily dose of \>=10 units/day. For participants currently taking pre-mixed insulin, the basal insulin component should be equivalent to a total daily dose of \>=10 units/day.
* is male, or is female who is not of reproductive potential or if of reproductive potential agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control during the study and for 14 days after the last dose of study medication

Exclusion Criteria:

* has had 1 or more severe hypoglycemic episodes associated with hypoglycemic seizure or loss of consciousness within the past 6 months
* history of ketoacidosis in the last 6 months
* participant, as assessed by the investigator, is not appropriate for or does not agree to target a fasting glucose of 70-100 mg/dL \[3.9 -5.6 mmol/L\].
* history of intolerance or hypersensitivity to Lantus™ or contraindication to Lantus™ or one of its excipients
* used a formulation of insulin glargine other than Lantus™
* has received injectable incretin-based therapy within the past 8 weeks
* on a weight loss program and not in the maintenance phase, or has started a weight loss medication within the past 8 weeks
* has undergone bariatric surgery within the past 12 months
* is likely to require treatment for 2 or more consecutive weeks or repeated courses of corticosteroids (note: inhaled, nasal, and topical corticosteroids are permitted)
* has undergone a surgical procedure within the past 4 weeks or has planned major surgery during the study
* has new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has any following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder
* has severe peripheral vascular disease
* has high blood pressure
* has chronic myopathy, or a progressive neurological or neuromuscular disorder
* has active nephropathy
* 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
* has human immunodeficiency virus (HIV)
* has a hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
* history of malignancy in the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
* history of melanoma, leukemia, lymphoma, or renal cell carcinoma
* is currently being treated for hyperthyroidism or has been on a stable dose of thyroid hormone replacement therapy for \<6 weeks
* is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence
* is pregnant or breast-feeding, or is expecting to conceive or donate eggs
* has donated blood products or has had phlebotomy of \>300 mL within the past 8 weeks or intends to donate blood products during the study
* has poor mental function or works the night shift

Primary outcomes:
measure: Primary: Change From Baseline in Hemoglobin A1c (A1C) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Any Confirmed Positive Anti-insulin Antibody (AIA) at Any Time Up Through Week 24
timeFrame: Up to Week 24
measure: Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 24
timeFrame: Up to Week 24
measure: Change From Baseline in AIA Titer After 24 Weeks of Treatment
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24
timeFrame: Up to Week 24
Secondary outcomes:
measure: Change From Baseline in A1C at Week 52
timeFrame: Baseline and Week 52
measure: Total Insulin Dose at Week 24
timeFrame: Week 24
measure: Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 24
timeFrame: Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Confirmed Positive AIA Up Through Week 52
timeFrame: Up to Week 52 including baseline
measure: Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 52
timeFrame: Up to Week 52
measure: Change From Baseline in AIA Titer After 52 Weeks of Treatment
timeFrame: Baseline and Week 52
measure: Total Insulin Dose at Week 52
timeFrame: Week 52
measure: Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 52
timeFrame: Week 52
measure: Change From Baseline in FPG at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 52
timeFrame: Up to Week 52
measure: Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in 7-point SMBG at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 24 Weeks of Treatment.
timeFrame: 24 weeks
measure: Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 52 Weeks of Treatment.
timeFrame: 52 weeks
measure: Basal Insulin Dose at Week 52
timeFrame: Week 52
measure: Basal Insulin Dose Per kg of Body Weight at Week 52
timeFrame: Week 52
measure: Bolus Insulin Dose at Week 52
timeFrame: Week 52
measure: Bolus Insulin Dose Per kg of Body Weight at Week 52
timeFrame: Week 52
measure: Basal Insulin Dose at Week 24
timeFrame: Week 24
measure: Basal Insulin Dose Per kg of Body Weight at Week 24
timeFrame: Week 24
measure: Bolus Insulin Dose at Week 24
timeFrame: Week 24
measure: Bolus Insulin Dose Per kg of Body Weight at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Home PD, Lam RLH, Carofano WL, Golm GT, Eldor R, Crutchlow MF, Marcos MC, Rosenstock J, Hollander PA, Gallwitz B. Efficacy and safety of MK-1293 insulin glargine compared with originator insulin glargine (Lantus) in type 1 diabetes: A randomized, open-label clinical trial. Diabetes Obes Metab. 2018 Sep;20(9):2220-2228. doi: 10.1111/dom.13354. Epub 2018 Jun 5.