Type 2 Diabetes Mellitus
Conditions
Brief summary
This 24-week study is a safety and efficacy comparison of MK-1293 and Lantus™ in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that after 24 weeks, the mean change in hemoglobin A1c (A1C) from baseline is non-inferior (with margin of 0.4%) in participants treated with MK-1293 compared with that in participants treated with Lantus™.
Interventions
DRUGMK-1293
MK-1293 (insulin glargine) 100 units/mL administered subcutaneously once daily for 24 weeks. Participants not taking insulin at study entry will initiate MK-1293 at 10 units daily. Participants taking insulin will initiate MK-1293 at an appropriate dose based on prior insulin dosing. After initiation, the dose will be titrated to the suggested target for fasting finger stick glucose. MK-1293 dosing once daily at times other than bedtime will be permitted for participants with a previously established dosing time.
DRUGLantus™
Lantus™ (insulin glargine \[rDNA origin\]) 100 units/mL administered subcutaneously once daily for 24 weeks. Participants not taking insulin at study entry will initiate Lantus™ at 10 units daily. Participants taking insulin will initiate Lantus™ at an appropriate dose based on prior insulin dosing. After initiation, the dose will be titrated to the suggested target for fasting finger stick glucose. Lantus™ dosing once daily at times other than bedtime will be permitted for participants with a previously established dosing time.
DRUGPrandial insulin
Participants taking prandial insulin will continue their current prandial insulin regimen during the insulin glargine titration. After the insulin glargine titration phase, the prandial insulin may be adjusted if the investigator determines it to be necessary for glucose control.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Type 2 Diabetes Mellitus (T2DM) as defined by the American Diabetes Association (ADA) or the European Association for the Study of Diabetes (EASD) * hemoglobin A1C of ≤11.0% and requires insulin for glycemic control * Body mass index (BMI) \<45 kg/m\^2
Exclusion criteria
* History of type 1 diabetes mellitus or a history of ketoacidosis, or has type 1 diabetes confirmed with a C-peptide \<0.7 ng/mL (0.23 nmol/L) * One or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within the past 6 months * History of intolerance or hypersensitivity to Lantus™ or contraindication to Lantus™ or one of its excipients based on the label of the country of the investigational site * On a weight loss program within the last 8 weeks * Received injectable incretin-based therapy (e.g., Victoza™, Byetta™) within the prior 8 weeks * Bariatric surgery within 12 months prior to signing the informed consent * Likely to require treatment for ≥2 consecutive weeks or repeated courses of corticosteroids * Undergone a surgical procedure within 4 weeks prior to signing informed consent or has planned major surgery during the study * New or worsening signs or symptoms of coronary heart disease or congestive heart failure within the last 3 months * Presence of any of the following during the last 3 months: acute coronary syndrome, coronary artery intervention, and/or stroke or transient ischemic neurological disorder * Severe peripheral vascular disease * Systolic blood pressure ≥ 160 mm Hg or a diastolic ≥95 mm Hg and blood pressure is not considered likely to be under these limits with an adjustment in antihypertensive medication * Chronic myopathy or a progressive neurological or neuromuscular disorder * 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 * Human immunodeficiency virus (HIV) * Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) * 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 * History of melanoma, leukemia, lymphoma, or renal cell carcinoma * Hyperthyroidism * On a stable dose of thyroid hormone replacement therapy for \<6 weeks * Uses recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence * Pregnant or breast-feeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug * 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 study * Poor mental function or any other reason to expect that the participant may have difficulty in complying with the requirements of the study * Clinically significant ECG abnormality which exposes the participant to risk by enrolling in the study * Positive urine pregnancy test * Participant is a night shift worker which causes difficulty complying with the overnight fast requirement and has potential for confounding the 7-point SMBG analysis * Participant, as assessed by the investigator, is not appropriate for or does not agree to target a fasting glucose of 70-100 mg/dL \[3.9 -5.6 mmol/L\] * Has used a formulation of glargine insulin other than Lantus™
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant Hemoglobin A1C Level at Week 24 | Baseline and Week 24 | A1C is measured as a percent. A1C is the key glycemic parameter which correlates with reduction of risk of diabetic complications. |
| Percentage of Participants With Confirmed Anti-Insulin Antibodies (AIA) up to Week 24 | Up to 24 weeks | Percentage of participants is a cumulative percentage of participants with any confirmed AIA (including baseline) up to Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing an AE Over the 24-week Treatment Period | Up to 24 weeks | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an AE. |
| Daily Basal Insulin Dose (Units) at Week 24 | Week 24 | The daily basal insulin dose (measured in units) for any given visit is defined as the average dose from the three most recent days preceding the visit date. |
| Daily Basal Insulin Dose Per Body Weight (Units/kg) at Week 24 | Week 24 | Basal insulin dose per body weight was calculated as total insulin dose (units) per day divided by body weight in kilograms (kg). |
| Change From Baseline in Participant Body Weight at Week 24 | Baseline and Week 24 | Change from baseline in participant body weight at Week 24. |
| Change From Baseline in Participant 7-Point Average of Self-Monitored Blood Glucose (SMBG) at Week 24 | Baseline and Week 24 | 7-Point Average of SMBG was defined as the mean of blood glucose measurements taken at the following 7 times: before morning meal, after morning meal, before midday meal, after midday meal, before evening meal, after evening meal or at bedtime, and between 2 AM and 4 AM. |
| Percentage of Participants With Hemoglobin A1C <7% at Week 24 | Week 24 | Percentage of participants with A1C \<7.0% (53 mmol/mol) at Week 24. |
| Percentage of Participants With Hemoglobin A1C <6.5% at Week 24 | Week 24 | Percentage of participants with A1C \<6.5% (48 mmol/mol) at Week 24. |
| Change From Baseline in Participant Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | Participants fasted (no food or drink except water and non-antihyperglycemic non-study medications as prescribed) for at least 8 hours prior to all study visits. |
| Percentage of Participants Experiencing an Adverse Event (AE) of Hypoglycemia Up to Week 24 | Up to 24 weeks | Symptomatic events assessed as likely to be hypoglycemia were to be reported by investigators as adverse events of hypoglycemia; a concurrent glucose measurement was not required. Asymptomatic events with confirmed glucose levels \</= 70mg/dL (\</= 3.9mmol/L) could also be reported as adverse events at the discretion of the investigator. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-1293 MK-1293 administered subcutaneously once daily. | 265 |
| Lantus™ Lantus™ administered subcutaneously once daily. | 266 |
| Total | 531 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 9 | 8 |
| Overall Study | Non-compliance with study drug | 1 | 0 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 8 |
Baseline characteristics
| Characteristic | MK-1293 | Lantus™ | Total |
|---|---|---|---|
| Age, Continuous | 56.9 Years STANDARD_DEVIATION 10 | 57.1 Years STANDARD_DEVIATION 9.8 | 57.0 Years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 113 Participants | 125 Participants | 238 Participants |
| Sex: Female, Male Male | 152 Participants | 141 Participants | 293 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 147 / 263 | 151 / 263 |
| serious Total, serious adverse events | 13 / 263 | 9 / 263 |
Outcome results
Primary
Change From Baseline in Participant Hemoglobin A1C Level at Week 24
A1C is measured as a percent. A1C is the key glycemic parameter which correlates with reduction of risk of diabetic complications.
Time frame: Baseline and Week 24
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1293 | Change From Baseline in Participant Hemoglobin A1C Level at Week 24 | -1.28 Percent A1C |
| Lantus™ | Change From Baseline in Participant Hemoglobin A1C Level at Week 24 | -1.30 Percent A1C |
95% CI: [-0.12, 0.18]
Primary
Percentage of Participants With Confirmed Anti-Insulin Antibodies (AIA) up to Week 24
Percentage of participants is a cumulative percentage of participants with any confirmed AIA (including baseline) up to Week 24.
Time frame: Up to 24 weeks
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1293 | Percentage of Participants With Confirmed Anti-Insulin Antibodies (AIA) up to Week 24 | 34.7 Percentage of participants |
| Lantus™ | Percentage of Participants With Confirmed Anti-Insulin Antibodies (AIA) up to Week 24 | 29.0 Percentage of participants |
95% CI: [-2.3, 13.7]
Secondary
Change From Baseline in Participant 7-Point Average of Self-Monitored Blood Glucose (SMBG) at Week 24
7-Point Average of SMBG was defined as the mean of blood glucose measurements taken at the following 7 times: before morning meal, after morning meal, before midday meal, after midday meal, before evening meal, after evening meal or at bedtime, and between 2 AM and 4 AM.
Time frame: Baseline and Week 24
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1293 | Change From Baseline in Participant 7-Point Average of Self-Monitored Blood Glucose (SMBG) at Week 24 | -30.7 mg/dL |
| Lantus™ | Change From Baseline in Participant 7-Point Average of Self-Monitored Blood Glucose (SMBG) at Week 24 | -27.3 mg/dL |
95% CI: [-11.3, 4.4]
Secondary
Change From Baseline in Participant Body Weight at Week 24
Change from baseline in participant body weight at Week 24.
Time frame: Baseline and Week 24
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-1293 | Change From Baseline in Participant Body Weight at Week 24 | 1.3 kilograms | Standard Deviation 3.6 |
| Lantus™ | Change From Baseline in Participant Body Weight at Week 24 | 1.4 kilograms | Standard Deviation 4.5 |
Secondary
Change From Baseline in Participant Fasting Plasma Glucose (FPG) at Week 24
Participants fasted (no food or drink except water and non-antihyperglycemic non-study medications as prescribed) for at least 8 hours prior to all study visits.
Time frame: Baseline and Week 24
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1293 | Change From Baseline in Participant Fasting Plasma Glucose (FPG) at Week 24 | -35.0 mg/dL |
| Lantus™ | Change From Baseline in Participant Fasting Plasma Glucose (FPG) at Week 24 | -38.4 mg/dL |
95% CI: [-3.7, 10.7]
Secondary
Daily Basal Insulin Dose Per Body Weight (Units/kg) at Week 24
Basal insulin dose per body weight was calculated as total insulin dose (units) per day divided by body weight in kilograms (kg).
Time frame: Week 24
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1293 | Daily Basal Insulin Dose Per Body Weight (Units/kg) at Week 24 | 0.53 Units/kg |
| Lantus™ | Daily Basal Insulin Dose Per Body Weight (Units/kg) at Week 24 | 0.51 Units/kg |
95% CI: [-0.02, 0.05]
Secondary
Daily Basal Insulin Dose (Units) at Week 24
The daily basal insulin dose (measured in units) for any given visit is defined as the average dose from the three most recent days preceding the visit date.
Time frame: Week 24
Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1293 | Daily Basal Insulin Dose (Units) at Week 24 | 48.2 Units |
| Lantus™ | Daily Basal Insulin Dose (Units) at Week 24 | 46.9 Units |
95% CI: [-2.2, 4.9]
Secondary
Percentage of Participants Experiencing an Adverse Event (AE) of Hypoglycemia Up to Week 24
Symptomatic events assessed as likely to be hypoglycemia were to be reported by investigators as adverse events of hypoglycemia; a concurrent glucose measurement was not required. Asymptomatic events with confirmed glucose levels \</= 70mg/dL (\</= 3.9mmol/L) could also be reported as adverse events at the discretion of the investigator.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1293 | Percentage of Participants Experiencing an Adverse Event (AE) of Hypoglycemia Up to Week 24 | 54.0 Percentage of participants |
| Lantus™ | Percentage of Participants Experiencing an Adverse Event (AE) of Hypoglycemia Up to Week 24 | 54.0 Percentage of participants |
95% CI: [-8.5, 8.5]
Secondary
Percentage of Participants Experiencing an AE Over the 24-week Treatment Period
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an AE.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1293 | Percentage of Participants Experiencing an AE Over the 24-week Treatment Period | 78.3 Percentage of participants |
| Lantus™ | Percentage of Participants Experiencing an AE Over the 24-week Treatment Period | 71.5 Percentage of participants |
95% CI: [-0.6, 14.2]
Secondary
Percentage of Participants With Hemoglobin A1C <6.5% at Week 24
Percentage of participants with A1C \<6.5% (48 mmol/mol) at Week 24.
Time frame: Week 24
Population: The analysis population included all randomized, treated participants with a Week 24 A1C measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1293 | Percentage of Participants With Hemoglobin A1C <6.5% at Week 24 | 21.6 Percentage of participants |
| Lantus™ | Percentage of Participants With Hemoglobin A1C <6.5% at Week 24 | 22.4 Percentage of participants |
95% CI: [-8.3, 6.5]
Secondary
Percentage of Participants With Hemoglobin A1C <7% at Week 24
Percentage of participants with A1C \<7.0% (53 mmol/mol) at Week 24.
Time frame: Week 24
Population: The analysis population included all randomized, treated participants with a Week 24 A1C measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1293 | Percentage of Participants With Hemoglobin A1C <7% at Week 24 | 46.5 Percentage of participants |
| Lantus™ | Percentage of Participants With Hemoglobin A1C <7% at Week 24 | 43.7 Percentage of participants |
95% CI: [-6.1, 11.6]