Diabetes Mellitus, Non-Insulin-Dependent
Conditions
Brief summary
The multiple dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-0941 in Japanese patients with Type 2 Diabetes.
Interventions
DRUGPlacebo
Placebo tablets before every meal (q.a.c) Treatment period is 5 days.
DRUGMK-0941
MK-0941 5 mg tablets q.a.c.; 10 mg tablets q.a.c.; 20 mg tablets q.a.c.; or 40 mg tablets q.a.c. Treatment period is 5 days.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Japanese Male or Female between 20 to 65 years of age * Diagnosis of Type 2 Diabetes * Patient being treated by diet and exercise alone
Exclusion criteria
* Patient has a history of Type 1 Diabetes * Patient is being treated with glaucoma medications * Patient has donated blood or participated in another clinical study in the past 12 weeks * Patient is a regular user of any illicit drugs or has a history of drug, including alcohol, abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to 14 days after last dose of study drug | 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 study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 8 days after last dose of study drug during Period 1 and for up to 14 days after last dose of study drug during Period 2. |
| Number of Participants Who Discontinued Study Drug Due to an AE | Up to 14 days after last dose of study drug | 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 study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 8 days after last dose of study drug during Period 1 and for up to 14 days after last dose of study drug during Period 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Up to 72 hours after study drug administration | Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period. |
| Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Up to 72 hours after study drug administration | Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period. |
| Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Up to 72 hours after study drug administration | Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period. |
| Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | Day 5 and Day 1 | Geometric Mean of the Day 5 to Day 1 Accumulation Ratio |
| Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Up to 72 hours after study drug administration | Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period. |
| Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Up to 72 hours after study drug administration | Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/MK-0941 20mg Participants received Placebo during Period 1 and MK-0941 20 mg during Period 2 | 2 |
| MK-0941 5mg/Placebo Participants received MK-0941 5 mg during Period 1 and Placebo during Period 2 | 2 |
| MK-0941 5mg/MK-0941 20mg Participants received MK-0941 5 mg during Period 1 and MK-0941 20 mg during Period 2 | 4 |
| Placebo/MK-0941 40mg Participants received Placebo during Period 1 and MK-0941 40 mg during Period 2 | 2 |
| MK-0941 10mg/Placebo Participants received MK-0941 10 mg during Period 1 and Placebo during Period 2 | 2 |
| MK-0941 10mg/MK-0941 40mg Participants received MK-0941 10 mg during Period 1 and MK-0941 40 mg during Period 2 | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo/MK-0941 20mg | MK-0941 5mg/Placebo | MK-0941 5mg/MK-0941 20mg | Placebo/MK-0941 40mg | MK-0941 10mg/Placebo | MK-0941 10mg/MK-0941 40mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.0 years STANDARD_DEVIATION 12.73 | 48.5 years STANDARD_DEVIATION 2.12 | 45.5 years STANDARD_DEVIATION 16.58 | 57.0 years STANDARD_DEVIATION 7.07 | 53.5 years STANDARD_DEVIATION 10.6 | 51.5 years STANDARD_DEVIATION 11.36 | 50.4 years STANDARD_DEVIATION 10.82 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 3 Participants | 14 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 8 | 2 / 6 | 2 / 6 | 2 / 6 | 2 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 |
Outcome results
Primary
Number of Participants Who Discontinued Study Drug Due to an AE
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 study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 8 days after last dose of study drug during Period 1 and for up to 14 days after last dose of study drug during Period 2.
Time frame: Up to 14 days after last dose of study drug
Population: Safety Population, consisting of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Discontinued Study Drug Due to an AE | 0 participants |
| MK-0941 5mg | Number of Participants Who Discontinued Study Drug Due to an AE | 0 participants |
| MK-0941 10mg | Number of Participants Who Discontinued Study Drug Due to an AE | 0 participants |
| MK-0941 20mg | Number of Participants Who Discontinued Study Drug Due to an AE | 0 participants |
| MK-0941 40mg | Number of Participants Who Discontinued Study Drug Due to an AE | 0 participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event (AE)
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 study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 8 days after last dose of study drug during Period 1 and for up to 14 days after last dose of study drug during Period 2.
Time frame: Up to 14 days after last dose of study drug
Population: Safety Population, consisting of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Experienced at Least One Adverse Event (AE) | 2 participants |
| MK-0941 5mg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 2 participants |
| MK-0941 10mg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 2 participants |
| MK-0941 20mg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 2 participants |
| MK-0941 40mg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 2 participants |
Secondary
Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941
Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period.
Time frame: Up to 72 hours after study drug administration
Population: Participants with a t1/2 measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 1 | 5.4 hr | Standard Deviation 1.5 |
| Placebo | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 5 | 7.7 hr | Standard Deviation 2 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 5 | 8.3 hr | Standard Deviation 4.1 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 1 | 4.4 hr | Standard Deviation 1.2 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 1 | 4.3 hr | Standard Deviation 1.1 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 5 | 9.9 hr | Standard Deviation 7.2 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 1 | 3.9 hr | Standard Deviation 1.1 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Apparent Terminal Elimination Half-life (t1/2) of MK-0941 | Day 5 | 9.1 hr | Standard Deviation 7.3 |
Secondary
Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941
Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period.
Time frame: Up to 72 hours after study drug administration
Population: Participants with an AUC(0-24hr) measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 1 | 754 nmol*hr/L | Standard Deviation 165 |
| Placebo | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 5 | 883 nmol*hr/L | Standard Deviation 157 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 5 | 2360 nmol*hr/L | Standard Deviation 1260 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 1 | 1900 nmol*hr/L | Standard Deviation 885 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 5 | 3560 nmol*hr/L | Standard Deviation 863 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 1 | 3230 nmol*hr/L | Standard Deviation 654 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 5 | 9730 nmol*hr/L | Standard Deviation 3140 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Area Under the Concentration-time Curve (AUC)(0-24hr) of MK-0941 | Day 1 | 8700 nmol*hr/L | Standard Deviation 2190 |
Secondary
Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr)
Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period.
Time frame: Up to 72 hours after study drug administration
Population: Participants with a C24hr measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 1 | 8.9 nmol/L | Standard Deviation 3.7 |
| Placebo | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 5 | 9.5 nmol/L | Standard Deviation 2.1 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 5 | 26.0 nmol/L | Standard Deviation 7.4 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 1 | 14.6 nmol/L | Standard Deviation 3.7 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 5 | 38.5 nmol/L | Standard Deviation 12.5 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 1 | 27.9 nmol/L | Standard Deviation 12.8 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 5 | 112.8 nmol/L | Standard Deviation 41.4 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Concentration of MK-0941 at 24 Hours (C24hr) | Day 1 | 66.4 nmol/L | Standard Deviation 16.4 |
Secondary
Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr
Geometric Mean of the Day 5 to Day 1 Accumulation Ratio
Time frame: Day 5 and Day 1
Population: All participants with pharmacokinetic measurements on Days 1 and 5
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | AUC(0-24hr) Day 5/Day 1 Accumulation Ratio | 1.18 Ratio |
| Placebo | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | C24hr Day 5/Day 1 Accumulation Ratio | 1.1 Ratio |
| Placebo | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | Cmax Day 5/Day 1 Accumulation Ratio | 1.21 Ratio |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | AUC(0-24hr) Day 5/Day 1 Accumulation Ratio | 1.28 Ratio |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | C24hr Day 5/Day 1 Accumulation Ratio | 1.77 Ratio |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | Cmax Day 5/Day 1 Accumulation Ratio | 1.18 Ratio |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | Cmax Day 5/Day 1 Accumulation Ratio | 1.02 Ratio |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | AUC(0-24hr) Day 5/Day 1 Accumulation Ratio | 1.09 Ratio |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | C24hr Day 5/Day 1 Accumulation Ratio | 1.44 Ratio |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | AUC(0-24hr) Day 5/Day 1 Accumulation Ratio | 1.1 Ratio |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | C24hr Day 5/Day 1 Accumulation Ratio | 1.65 Ratio |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Day 5 to Day 1 Accumulation Ratio for AUC (0-24hr), Cmax, and C24hr | Cmax Day 5/Day 1 Accumulation Ratio | 0.90 Ratio |
Secondary
Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941
Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period.
Time frame: Up to 72 hours after study drug administration
Population: Participants with a Cmax measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 1 | 105 nmol/L | Standard Deviation 21.5 |
| Placebo | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 5 | 128 nmol/L | Standard Deviation 26.2 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 5 | 292 nmol/L | Standard Deviation 108 |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 1 | 255 nmol/L | Standard Deviation 116 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 1 | 487 nmol/L | Standard Deviation 58.3 |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 5 | 509 nmol/L | Standard Deviation 140 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 1 | 1340 nmol/L | Standard Deviation 269 |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Maximum Concentration (Cmax) of MK-0941 | Day 5 | 1240 nmol/L | Standard Deviation 424 |
Secondary
Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941
Blood samples for measurement of plasma pharmacokinetic parameters were collected from predose to up to 24 hours postdose on Day 1 and from predose to up to 72 hours postdose on Day 5 in each treatment period.
Time frame: Up to 72 hours after study drug administration
Population: Participants with a Tmax measurement
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 1 | 3.5 hr |
| Placebo | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 5 | 1.0 hr |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 5 | 1.0 hr |
| MK-0941 5mg | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 1 | 6.0 hr |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 1 | 1.0 hr |
| MK-0941 10mg | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 5 | 6.0 hr |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 1 | 1.0 hr |
| MK-0941 20mg | Plasma Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of MK-0941 | Day 5 | 6.0 hr |