Type 2 Diabetes Mellitus
Conditions
Brief summary
A study to assess safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-0941 in Type 2 diabetics being treated with basal insulin.
Interventions
DRUGMK-0941
In Titration Scheme #1, MK-0941/matching placebo was initiated at 10-mg q.a.c. dose and increased on a daily basis (Titration Dose \[TD\] Days 1 to 4 of the Titration Phase 1) in 10-mg q.a.c. increments. Titration Scheme #2 was a flexible-dose titration scheme in which MK-0941/matching placebo was given at a dose determined by a pre-prandial plasma glucose concentration for the subsequent meal on the previous day of administration on Days 1 to 4 of the Titration Phase 2.
DRUGPlacebo
10 mg Placebo (Pbo), 20 mg Pbo, 30 mg Pbo or 40 mg Pbo q.a.c.
DRUGLANTUS insulin
LANTUS insulin dose will be similar to participant's previous dose of immediate or long-acting insulin
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female (of non-childbearing potential) between 18 to 70 years of age * Diagnosed with Type 2 Diabetes and currently being treated with basal insulin * Smokers may participate, but they are limited to 10 cigarettes per day while at the clinic and must follow clinic smoking rules
Exclusion criteria
* History of Type 1 diabetes * Treated with peroxisome proliferator-activated receptor (PPAR) agonists within 12 weeks prior to study start * History of severe hypoglycemia * Allergic to insulin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Experienced an Adverse Event During the Study | 39 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event - Titration Scheme 1 | 25 days | In Titration Scheme #1, MK-0941/matching placebo was initiated at 10-mg q.a.c. dose and increased on a daily basis in 10-mg q.a.c. increments on Titration Dose \[TD\] Days 1 to 4 of the Titration Phase 1 of the study. |
| Number of Participants Who Experienced an Adverse Event - Titration Scheme 2 | 25 days | Titration Scheme #2 (Titration Phase, Days 1 to 4) was a flexible-dose titration scheme in which MK-0941/matching placebo was given at a dose determined by a pre-prandial plasma glucose concentration for the subsequent meal on the previous day of administration. |
| 24-Hour Weighted Mean Blood Glucose Levels (mg/dL) by Treatment Group on Day 7 | 24 hours | Measurement of the 24-hour weighted mean blood glucose levels of participants receiving MK-0941 or placebo while on basal insulin on Day 7. |
| Number of Participants Who Experienced an Adverse Event During the Outpatient Treatment Period | Outpatient Days 1 to 14 | During the Outpatient Treatment Period, participants were followed for an additional 2 weeks while at home. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0941 Participants receiving multiple daily before each meal (q.a.c.) administrations of MK-0941 while on basal insulin. | 47 |
| Placebo Participants receiving placebo while on basal insulin. | 23 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Clinical Adverse Event | 1 | 2 |
| Overall Study | Laboratory Adverse Event | 0 | 2 |
| Overall Study | Not reported | 2 | 2 |
Baseline characteristics
| Characteristic | MK-0941 | Placebo | Total |
|---|---|---|---|
| Age, Customized 22 to 69 years | 47 participants | 23 participants | 70 participants |
| Age, Customized <22 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >69 years | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 19 Participants | 13 Participants | 32 Participants |
| Sex: Female, Male Male | 28 Participants | 10 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 23 | 21 / 24 | 11 / 12 | 10 / 11 |
| serious Total, serious adverse events | 0 / 23 | 1 / 24 | 0 / 12 | 1 / 11 |
Outcome results
Primary
Number of Participants Who Experienced an Adverse Event During the Study
Time frame: 39 days
Population: All participants who experienced one or more adverse events during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants Who Experienced an Adverse Event During the Study | 46 participants |
| Placebo | Number of Participants Who Experienced an Adverse Event During the Study | 21 participants |
Secondary
24-Hour Weighted Mean Blood Glucose Levels (mg/dL) by Treatment Group on Day 7
Measurement of the 24-hour weighted mean blood glucose levels of participants receiving MK-0941 or placebo while on basal insulin on Day 7.
Time frame: 24 hours
Population: All participants who had 24-hour weighted mean blood glucose levels evaluated on Day 7
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK-0941 | 24-Hour Weighted Mean Blood Glucose Levels (mg/dL) by Treatment Group on Day 7 | 155.5 mg/dL | Standard Deviation 62.9 |
| Placebo | 24-Hour Weighted Mean Blood Glucose Levels (mg/dL) by Treatment Group on Day 7 | 151.3 mg/dL | Standard Deviation 47.4 |
| Placebo | 24-Hour Weighted Mean Blood Glucose Levels (mg/dL) by Treatment Group on Day 7 | 201.6 mg/dL | Standard Deviation 54.9 |
Comparison: For the least square mean difference - baseline in the ANOVA model = glucose value at Titration Day 1 pre-Breakfast for Titration Group 1p-value: 0.00190% CI: [22.71, 69.5]ANOVA
Comparison: For the least square mean difference - baseline in the ANOVA model = glucose value at Titration Day 1 pre-breakfast for Titration Group 2p-value: <0.00190% CI: [27.68, 72.88]ANOVA
Secondary
Number of Participants Who Experienced an Adverse Event During the Outpatient Treatment Period
During the Outpatient Treatment Period, participants were followed for an additional 2 weeks while at home.
Time frame: Outpatient Days 1 to 14
Population: All participants who experienced one or more adverse events during the Outpatient Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants Who Experienced an Adverse Event During the Outpatient Treatment Period | 20 participants |
| Placebo | Number of Participants Who Experienced an Adverse Event During the Outpatient Treatment Period | 11 participants |
Secondary
Number of Participants Who Experienced an Adverse Event - Titration Scheme 1
In Titration Scheme #1, MK-0941/matching placebo was initiated at 10-mg q.a.c. dose and increased on a daily basis in 10-mg q.a.c. increments on Titration Dose \[TD\] Days 1 to 4 of the Titration Phase 1 of the study.
Time frame: 25 days
Population: All participants who experienced one or more adverse events within 25 days of Titration Scheme 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants Who Experienced an Adverse Event - Titration Scheme 1 | 20 participants |
| Placebo | Number of Participants Who Experienced an Adverse Event - Titration Scheme 1 | 11 participants |
Secondary
Number of Participants Who Experienced an Adverse Event - Titration Scheme 2
Titration Scheme #2 (Titration Phase, Days 1 to 4) was a flexible-dose titration scheme in which MK-0941/matching placebo was given at a dose determined by a pre-prandial plasma glucose concentration for the subsequent meal on the previous day of administration.
Time frame: 25 days
Population: All participants who experienced one or more adverse events within 25 days of Titration Scheme 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants Who Experienced an Adverse Event - Titration Scheme 2 | 22 participants |
| Placebo | Number of Participants Who Experienced an Adverse Event - Titration Scheme 2 | 10 participants |