A Study of the Safety and Efficacy of MK-1293 Compared to Lantus™ in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003)
Primary Purpose
Type 1 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
MK-1293
Lantus™
Prandial Insulin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
MK-1293
Lantus
Arm Description
MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post randomization to the suggested target for fasting fingerstick glucose levels of >70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of >70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Outcomes
Primary Outcome Measures
Primary: Change From Baseline in Hemoglobin A1c (A1C) at Week 24
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 24 A1C minus the Week 0 A1C.
Percentage of Participants With Any Confirmed Positive Anti-insulin Antibody (AIA) at Any Time Up Through Week 24
Percentage of participants with confirmed positive AIA at any time up through Week 24 including baseline.
Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 24
Percentage of participants who became positive to AIA at or before Week 24, among participants who were AIA negative at baseline.
Change From Baseline in AIA Titer After 24 Weeks of Treatment
This immunogenicity analysis will assess the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 24 weeks of treatment. This change from baseline reflects the Week 24 AIA titer minus the Week 0 AIA titer.
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INab) development up through 24 weeks of treatment.
Secondary Outcome Measures
Change From Baseline in A1C at Week 52
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 52 A1C minus the Week 0 A1C.
Total Insulin Dose at Week 24
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 24
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Blood glucose was measured on a fasting basis (collected after a 10-hour fast). FPG is expressed as mg/dL. This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.
Percentage of Participants With Confirmed Positive AIA Up Through Week 52
Percentage of participants with confirmed positive AIA at any time up through Week 52 including baseline.
Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 52
Percentage of participants who became positive to AIA at or before Week 52, among participants who were AIA negative at baseline.
Change From Baseline in AIA Titer After 52 Weeks of Treatment
This immunogenicity analysis assessed the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 52 weeks of treatment. This change from baseline reflects the AIA titers at Week 52 minus the AIA titers at Week 0.
Total Insulin Dose at Week 52
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 52
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Change From Baseline in FPG at Week 52
Blood glucose was measured on a fasting basis (collected after a 10-hour fast). This change from baseline reflects the FPG level at Week 52 minus the FPG level at Week 0.
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 52
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Thought Week 52. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INAb) development up through 52 weeks of treatment.
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) at Week 24
The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning.
Change From Baseline in 7-point SMBG at Week 52
The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning.
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 24 Weeks of Treatment.
Percentage of participants attaining A1C glycemic goals of <7.0% and <6.5% after 24 weeks of treatment.
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 52 Weeks of Treatment.
Percentage of participants attaining A1C glycemic goals of <7.0% and <6.5% after 52 weeks of treatment.
Basal Insulin Dose at Week 52
Basal Insulin Dose at Week 52.
Basal Insulin Dose Per kg of Body Weight at Week 52
Basal Insulin Dose per kg of Body Weight at Week 52.
Bolus Insulin Dose at Week 52
Bolus Insulin Dose at Week 52.
Bolus Insulin Dose Per kg of Body Weight at Week 52
Bolus Insulin Dose per kg of Body Weight at Week 52.
Basal Insulin Dose at Week 24
Basal Insulin Dose at Week 24.
Basal Insulin Dose Per kg of Body Weight at Week 24
Basal Insulin Dose per kg of Body Weight at Week 24.
Bolus Insulin Dose at Week 24
Bolus Insulin Dose at Week 24.
Bolus Insulin Dose Per kg of Body Weight at Week 24
Bolus Insulin Dose per kg of Body Weight at Week 24.
Full Information
NCT ID
NCT02059161
First Posted
February 7, 2014
Last Updated
August 7, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02059161
Brief Title
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
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 17, 2013 (Actual)
Primary Completion Date
May 4, 2015 (Actual)
Study Completion Date
November 12, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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™.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
508 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-1293
Arm Type
Experimental
Arm Description
MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post randomization to the suggested target for fasting fingerstick glucose levels of >70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Arm Title
Lantus
Arm Type
Active Comparator
Arm Description
Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of >70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Intervention Type
Drug
Intervention Name(s)
MK-1293
Intervention Description
MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Initial dose will be determined based on the participant's previous insulin therapy. Thereafter, the dose will be titrated to the suggested target for fasting fingerstick glucose levels. MK-1293 dosing once daily at times other than bedtime will be permitted for participants with a previously established dosing time.
Intervention Type
Drug
Intervention Name(s)
Lantus™
Other Intervention Name(s)
Insulin glargine
Intervention Description
Lantus™ dosed subcutaneously once daily at bedtime for 52 weeks. Initial dose will be determined based on the participant's previous insulin therapy. Thereafter, the dose will be titrated to the suggested target for fasting fingerstick glucose levels. Lantus™ dosing once daily at times other than bedtime will be permitted for participants with a previously established dosing time.
Intervention Type
Drug
Intervention Name(s)
Prandial Insulin
Intervention Description
Participants will continue their prandial insulin during the study.
Primary Outcome Measure Information:
Title
Primary: Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Description
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 24 A1C minus the Week 0 A1C.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With Any Confirmed Positive Anti-insulin Antibody (AIA) at Any Time Up Through Week 24
Description
Percentage of participants with confirmed positive AIA at any time up through Week 24 including baseline.
Time Frame
Up to Week 24
Title
Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 24
Description
Percentage of participants who became positive to AIA at or before Week 24, among participants who were AIA negative at baseline.
Time Frame
Up to Week 24
Title
Change From Baseline in AIA Titer After 24 Weeks of Treatment
Description
This immunogenicity analysis will assess the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 24 weeks of treatment. This change from baseline reflects the Week 24 AIA titer minus the Week 0 AIA titer.
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24
Description
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INab) development up through 24 weeks of treatment.
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in A1C at Week 52
Description
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 52 A1C minus the Week 0 A1C.
Time Frame
Baseline and Week 52
Title
Total Insulin Dose at Week 24
Description
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Time Frame
Week 24
Title
Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 24
Description
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Time Frame
Week 24
Title
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Description
Blood glucose was measured on a fasting basis (collected after a 10-hour fast). FPG is expressed as mg/dL. This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With Confirmed Positive AIA Up Through Week 52
Description
Percentage of participants with confirmed positive AIA at any time up through Week 52 including baseline.
Time Frame
Up to Week 52 including baseline
Title
Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 52
Description
Percentage of participants who became positive to AIA at or before Week 52, among participants who were AIA negative at baseline.
Time Frame
Up to Week 52
Title
Change From Baseline in AIA Titer After 52 Weeks of Treatment
Description
This immunogenicity analysis assessed the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 52 weeks of treatment. This change from baseline reflects the AIA titers at Week 52 minus the AIA titers at Week 0.
Time Frame
Baseline and Week 52
Title
Total Insulin Dose at Week 52
Description
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Time Frame
Week 52
Title
Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 52
Description
Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).
Time Frame
Week 52
Title
Change From Baseline in FPG at Week 52
Description
Blood glucose was measured on a fasting basis (collected after a 10-hour fast). This change from baseline reflects the FPG level at Week 52 minus the FPG level at Week 0.
Time Frame
Baseline and Week 52
Title
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 52
Description
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Thought Week 52. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INAb) development up through 52 weeks of treatment.
Time Frame
Up to Week 52
Title
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) at Week 24
Description
The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning.
Time Frame
Baseline and Week 24
Title
Change From Baseline in 7-point SMBG at Week 52
Description
The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning.
Time Frame
Baseline and Week 52
Title
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 24 Weeks of Treatment.
Description
Percentage of participants attaining A1C glycemic goals of <7.0% and <6.5% after 24 weeks of treatment.
Time Frame
24 weeks
Title
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 52 Weeks of Treatment.
Description
Percentage of participants attaining A1C glycemic goals of <7.0% and <6.5% after 52 weeks of treatment.
Time Frame
52 weeks
Title
Basal Insulin Dose at Week 52
Description
Basal Insulin Dose at Week 52.
Time Frame
Week 52
Title
Basal Insulin Dose Per kg of Body Weight at Week 52
Description
Basal Insulin Dose per kg of Body Weight at Week 52.
Time Frame
Week 52
Title
Bolus Insulin Dose at Week 52
Description
Bolus Insulin Dose at Week 52.
Time Frame
Week 52
Title
Bolus Insulin Dose Per kg of Body Weight at Week 52
Description
Bolus Insulin Dose per kg of Body Weight at Week 52.
Time Frame
Week 52
Title
Basal Insulin Dose at Week 24
Description
Basal Insulin Dose at Week 24.
Time Frame
Week 24
Title
Basal Insulin Dose Per kg of Body Weight at Week 24
Description
Basal Insulin Dose per kg of Body Weight at Week 24.
Time Frame
Week 24
Title
Bolus Insulin Dose at Week 24
Description
Bolus Insulin Dose at Week 24.
Time Frame
Week 24
Title
Bolus Insulin Dose Per kg of Body Weight at Week 24
Description
Bolus Insulin Dose per kg of Body Weight at Week 24.
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
29766635
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.
Results Reference
derived
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A Study of the Safety and Efficacy of MK-1293 Compared to Lantus™ in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003)
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