Type 2 Diabetes
Conditions
Brief summary
This study will asses the safety, tolerability, multiple-dose pharmacokinetics and pharmacodynamics of MK1006 in participants with type 2 diabetes.
Interventions
DRUGMK-1006
MK-1006 capsules (10 mg and 20 mg) administered orally from 20 mg to 120 mg per dose over a multiple dosing period.
Dose-matched MK-1006 placebo capsules (1 mg, 10 mg and 20 mg) administered orally over a multiple dosing period.
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant has a BMI less than or equal to 42 kg/m\^2 at the screening visit * Participant has been diagnosed with Type 2 Diabetes that is being treated either by diet and exercise alone or by single or combination oral anti-hyperglycemic medications * Participant is willing to follow a diet containing approximately 50% carbohydrates, 20% protein, and 30% fat during the study * Participant is a nonsmoker and has not used nicotine containing products for \ 6 months before start of study
Exclusion criteria
* Participant must not be treated with three or more oral anti-hyperglycemic medications, insulin, or PPAR-gamma agonists * Participant has a history of stroke, chronic seizures, or a major neurological disorder * Participant has had an eye infection or other inflammatory eye condition within 2 weeks of first dose of study drug * Participant has glaucoma or is blind * Participant has a condition known to be related to cataract development * Participant has had or will have incisional eye surgery within 6 months before screening or has had laser surgery (other than Lasik) within 3 months of screening * Participant has a history of type 1 diabetes or ketoacidosis * Participant cannot stop taking certain current medications during the study * Participant consumes greater than 3 alcoholic beverages per day * Participant consumes more than 6 servings of caffeinated beverages per day (1 serving is \ 120 mg caffeine) * Participant has a history of significant multiple or severe allergies or has had a reaction to or is intolerant of prescription/non-prescription drugs or food * Participant uses recreational drugs or has had a history of drug abuse within 6 months of start of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) On Study | From Day 1 through the end of poststudy period (up to Day 25) | An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the study treatment, was also an adverse event. |
| Number of Participants Who Discontinued Treatment Due to an AE | From Day 1 through the end of poststudy period (up to Day 25) | An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the study treatment, was also an adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Day -1 (pre-dose baseline), Day 1 (First Dosing Day), Day 10 (Last Dosing Day) | Plasma glucose concentration was determined using a glucometer and measured before drug was given to establish a baseline fasting plasma glucose concentration. Plasma glucose concentrations were then measured every \ 30 minutes over a 24 hour period after the Day 1 dose (First Dosing Day) and after the Day 10 dose (Last Dosing Day) to obtain a weighted mean average value for Day 1 and for Day 10. Results were expressed as the change from baseline to the Day 1 weighted average (First Dosing Day), and as the change from baseline to the Day 10 weighted average (Last Dosing Day). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Treated Participants After a 2-week run-in/wash-off period, participants received doses of MK-1006 or matching placebo over a multiple-dosing period while remaining domiciled in the Clinical Research Unit (CRU). | 112 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Laboratory Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Treated Participants |
|---|---|
| Age, Continuous | 53.1 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 4 / 6 | 5 / 6 | 2 / 6 | 4 / 6 | 6 / 7 | 15 / 20 | 16 / 20 | 22 / 29 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 1 / 20 | 0 / 20 | 1 / 29 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events (AEs) On Study
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the study treatment, was also an adverse event.
Time frame: From Day 1 through the end of poststudy period (up to Day 25)
Population: All Participants as Treated (APaT); All participants who received at least one dose of the investigational drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1006 20 mg Once Daily (Panel A) | Number of Participants Experiencing Adverse Events (AEs) On Study | 1 participants |
| MK-1006 40 mg Once Daily (Panel B) | Number of Participants Experiencing Adverse Events (AEs) On Study | 1 participants |
| MK-1006 80 mg Once Daily (Panel C) | Number of Participants Experiencing Adverse Events (AEs) On Study | 4 participants |
| MK-1006 120 mg Once Daily (Panel D) | Number of Participants Experiencing Adverse Events (AEs) On Study | 5 participants |
| MK-1006 20 mg Twice Daily (Panel E) | Number of Participants Experiencing Adverse Events (AEs) On Study | 4 participants |
| MK-1006 30 mg Twice Daily (Panel F) | Number of Participants Experiencing Adverse Events (AEs) On Study | 4 participants |
| MK-1006 50 mg Twice Daily (Panel G) | Number of Participants Experiencing Adverse Events (AEs) On Study | 6 participants |
| MK-1006 120 mg Once Daily Outpatient (Panel H) | Number of Participants Experiencing Adverse Events (AEs) On Study | 15 participants |
| MK-1006 50 mg Twice Daily Outpatient (Panel I) | Number of Participants Experiencing Adverse Events (AEs) On Study | 16 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) On Study | 22 participants |
Primary
Number of Participants Who Discontinued Treatment Due to an AE
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the study treatment, was also an adverse event.
Time frame: From Day 1 through the end of poststudy period (up to Day 25)
Population: All Participants as Treated (APaT); All participants who received at least one dose of the investigational drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1006 20 mg Once Daily (Panel A) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 40 mg Once Daily (Panel B) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 80 mg Once Daily (Panel C) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 120 mg Once Daily (Panel D) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 20 mg Twice Daily (Panel E) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 30 mg Twice Daily (Panel F) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 50 mg Twice Daily (Panel G) | Number of Participants Who Discontinued Treatment Due to an AE | 0 participants |
| MK-1006 120 mg Once Daily Outpatient (Panel H) | Number of Participants Who Discontinued Treatment Due to an AE | 1 participants |
| MK-1006 50 mg Twice Daily Outpatient (Panel I) | Number of Participants Who Discontinued Treatment Due to an AE | 1 participants |
| Placebo | Number of Participants Who Discontinued Treatment Due to an AE | 1 participants |
Secondary
Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG)
Plasma glucose concentration was determined using a glucometer and measured before drug was given to establish a baseline fasting plasma glucose concentration. Plasma glucose concentrations were then measured every \ 30 minutes over a 24 hour period after the Day 1 dose (First Dosing Day) and after the Day 10 dose (Last Dosing Day) to obtain a weighted mean average value for Day 1 and for Day 10. Results were expressed as the change from baseline to the Day 1 weighted average (First Dosing Day), and as the change from baseline to the Day 10 weighted average (Last Dosing Day).
Time frame: Day -1 (pre-dose baseline), Day 1 (First Dosing Day), Day 10 (Last Dosing Day)
Population: Per-Protocol Population; subset of participants who complied with the protocol sufficiently in terms of considerations as exposure to treatment, availability of measurements and absence of major protocol violations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-1006 20 mg Once Daily (Panel A) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | 3.5 mg/dL | Standard Deviation 40.1 |
| MK-1006 20 mg Once Daily (Panel A) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -5.3 mg/dL | Standard Deviation 11.3 |
| MK-1006 40 mg Once Daily (Panel B) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -19.3 mg/dL | Standard Deviation 15.1 |
| MK-1006 40 mg Once Daily (Panel B) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | 0.8 mg/dL | Standard Deviation 73.8 |
| MK-1006 80 mg Once Daily (Panel C) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | -66.9 mg/dL | Standard Deviation 20.3 |
| MK-1006 80 mg Once Daily (Panel C) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -43.8 mg/dL | Standard Deviation 10.1 |
| MK-1006 120 mg Once Daily (Panel D) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | -7.4 mg/dL | Standard Deviation 51.4 |
| MK-1006 120 mg Once Daily (Panel D) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -41.5 mg/dL | Standard Deviation 6.3 |
| MK-1006 20 mg Twice Daily (Panel E) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | -40.3 mg/dL | Standard Deviation 8.7 |
| MK-1006 20 mg Twice Daily (Panel E) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -20.7 mg/dL | Standard Deviation 10.3 |
| MK-1006 30 mg Twice Daily (Panel F) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | -30.7 mg/dL | Standard Deviation 30.8 |
| MK-1006 30 mg Twice Daily (Panel F) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -26.4 mg/dL | Standard Deviation 20.3 |
| MK-1006 50 mg Twice Daily (Panel G) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | -42.5 mg/dL | Standard Deviation 18.6 |
| MK-1006 50 mg Twice Daily (Panel G) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | -62.1 mg/dL | Standard Deviation 18.8 |
| MK-1006 120 mg Once Daily Outpatient (Panel H) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | Last Dosing Day | 30.2 mg/dL | Standard Deviation 40.6 |
| MK-1006 120 mg Once Daily Outpatient (Panel H) | Least Squares Mean Change From Baseline in 24-Hour Weighted Mean Glucose (WMG) | First Dosing Day | 5.3 mg/dL | Standard Deviation 11.1 |
p-value: 0.01595% CI: [12.58, 62.68]Mixed Effect Model
p-value: <0.00195% CI: [67.56, 117.04]Mixed Effect Model