Type 2 Diabetes
Conditions
Brief summary
This study will assess the safety, tolerability and pharmacokinetics of sitagliptin in 10 to 17 year old diabetic patients.
Interventions
DRUGSitagliptin phosphate
Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of sitagliptin 50 mg tablet, sitagliptin 100 mg tablet, or sitagliptin 200 mg.
DRUGComparator: matching placebo
Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Males or females who are 10 - 17 years of age * History of type 2 diabetes * Nonsmoker * No clinical or laboratory evidence to indicate a diagnosis of type 1 diabetes
Exclusion criteria
* History of diabetic ketoacidosis * History of stroke, chronic seizures or major neurological disorder * Consumes alcohol * Consume more than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola or other beverages containing caffeine per day * Unable to swallow tablets * Has had surgery, donated or lost 1 unit of blood, or participated in another investigational study within a minimum of 4 weeks prior to starting the study * History of multiple and/or severe allergies or has had an allergic reaction to or significant intolerability to prescription or non-prescription drugs or food * Currently a regular user of any illicit drugs or has a history of drug or alcohol abuse * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases * Has an estimated creatinine clearance of less than or equal to 80 mL/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event | Pre-study through 10 to 14 days following administration of study drug | — |
| Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity Following a Single Dose of Sitagliptin | Pre-dose through 72 hours post-dose | Serum samples were used to determine the AUC from time 0 to infinity for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) Following a Single Dose of Sitagliptin | Pre-dose through 72 hours post-dose | Serum samples were used to determine the Cmax for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. |
| Time of Occurence of Maximum Concentration (Tmax) Following a Single Dose of Sitagliptin | Pre-dose through 72 hours post-dose | Serum samples were used to determine the Tmax for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. |
| Apparent Terminal Half-life (Apparent t1/2) Following a Single Dose of Sitagliptin | Pre-dose through 72 hours post-dose | Serum samples were used to determine the apparent t1/2 for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. |
| Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | Pre-dose through 24 hours post-dose | Plasma DPP-4 activity was analyzed using the 24-hour weighted average inhibition (WAI) and percent inhibition at 24 hours post-dose. WAI was defined as the AUC of inhibition divided by the length of the post-dose time interval. Positive values of WAI represent a decrease in DPP-4 activity. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 50 mg Participants who received a single oral dose of sitagliptin 50 mg. | 9 |
| Sitagliptin 100 mg Participants who received a single oral dose of sitagliptin 100 mg. | 9 |
| Sitagliptin 200 mg Participants who received a single oral dose of sitagliptin 200 mg. | 8 |
| Placebo Participants who received a single oral dose of a matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg. | 9 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Sitagliptin 50 mg | Sitagliptin 100 mg | Sitagliptin 200 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 13.9 years STANDARD_DEVIATION 2.52 | 14.3 years STANDARD_DEVIATION 1.41 | 14.8 years STANDARD_DEVIATION 1.75 | 14.1 years STANDARD_DEVIATION 2.26 | 14.3 years STANDARD_DEVIATION 1.98 |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 5 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 11 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 | 3 / 9 | 1 / 9 | 1 / 8 | 2 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 8 | 0 / 9 |
Outcome results
Primary
Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity Following a Single Dose of Sitagliptin
Serum samples were used to determine the AUC from time 0 to infinity for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups.
Time frame: Pre-dose through 72 hours post-dose
Population: All participants who received a single dose of sitagliptin 50 mg, 100 mg, or 200 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sitagliptin 50 mg | Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity Following a Single Dose of Sitagliptin | 3438 nM*hour |
| Sitagliptin 100 mg | Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity Following a Single Dose of Sitagliptin | 5869 nM*hour |
| Sitagliptin 200 mg | Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity Following a Single Dose of Sitagliptin | 12965 nM*hour |
Primary
Number of Participants Who Experienced at Least One Adverse Event
Time frame: Pre-study through 10 to 14 days following administration of study drug
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin 50 mg | Number of Participants Who Experienced at Least One Adverse Event | 3 participants |
| Sitagliptin 100 mg | Number of Participants Who Experienced at Least One Adverse Event | 1 participants |
| Sitagliptin 200 mg | Number of Participants Who Experienced at Least One Adverse Event | 1 participants |
| Placebo | Number of Participants Who Experienced at Least One Adverse Event | 2 participants |
Secondary
Apparent Terminal Half-life (Apparent t1/2) Following a Single Dose of Sitagliptin
Serum samples were used to determine the apparent t1/2 for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups.
Time frame: Pre-dose through 72 hours post-dose
Population: All participants who received a single dose of sitagliptin 50 mg, 100 mg, or 200 mg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin 50 mg | Apparent Terminal Half-life (Apparent t1/2) Following a Single Dose of Sitagliptin | 12.1 hours | Standard Deviation 1.7 |
| Sitagliptin 100 mg | Apparent Terminal Half-life (Apparent t1/2) Following a Single Dose of Sitagliptin | 11.2 hours | Standard Deviation 2.1 |
| Sitagliptin 200 mg | Apparent Terminal Half-life (Apparent t1/2) Following a Single Dose of Sitagliptin | 11.7 hours | Standard Deviation 1.8 |
Secondary
Maximum Concentration (Cmax) Following a Single Dose of Sitagliptin
Serum samples were used to determine the Cmax for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups.
Time frame: Pre-dose through 72 hours post-dose
Population: All participants who received a single dose of sitagliptin 50 mg, 100 mg, or 200 mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sitagliptin 50 mg | Maximum Concentration (Cmax) Following a Single Dose of Sitagliptin | 366 nM |
| Sitagliptin 100 mg | Maximum Concentration (Cmax) Following a Single Dose of Sitagliptin | 666 nM |
| Sitagliptin 200 mg | Maximum Concentration (Cmax) Following a Single Dose of Sitagliptin | 1876 nM |
Secondary
Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo
Plasma DPP-4 activity was analyzed using the 24-hour weighted average inhibition (WAI) and percent inhibition at 24 hours post-dose. WAI was defined as the AUC of inhibition divided by the length of the post-dose time interval. Positive values of WAI represent a decrease in DPP-4 activity.
Time frame: Pre-dose through 24 hours post-dose
Population: All participants who received a single dose of sitagliptin or placebo.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Sitagliptin 50 mg | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | 24-hour WAI of DPP-4 activity | 73.98 Percent inhibition |
| Sitagliptin 50 mg | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | DDP-4 activity at 24 hours post-dose | 53.98 Percent inhibition |
| Sitagliptin 100 mg | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | DDP-4 activity at 24 hours post-dose | 62.78 Percent inhibition |
| Sitagliptin 100 mg | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | 24-hour WAI of DPP-4 activity | 80.53 Percent inhibition |
| Sitagliptin 200 mg | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | 24-hour WAI of DPP-4 activity | 87.96 Percent inhibition |
| Sitagliptin 200 mg | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | DDP-4 activity at 24 hours post-dose | 75.76 Percent inhibition |
| Placebo | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | 24-hour WAI of DPP-4 activity | 6.76 Percent inhibition |
| Placebo | Plasma Dipeptidyl Peptidase-4 (DPP-4) Activity Following a Single Dose of Sitagliptin or Placebo | DDP-4 activity at 24 hours post-dose | 3.57 Percent inhibition |
Secondary
Time of Occurence of Maximum Concentration (Tmax) Following a Single Dose of Sitagliptin
Serum samples were used to determine the Tmax for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups.
Time frame: Pre-dose through 72 hours post-dose
Population: All participants who received a single dose of sitagliptin 50 mg, 100 mg, or 200 mg.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin 50 mg | Time of Occurence of Maximum Concentration (Tmax) Following a Single Dose of Sitagliptin | 3.0 hours |
| Sitagliptin 100 mg | Time of Occurence of Maximum Concentration (Tmax) Following a Single Dose of Sitagliptin | 3.0 hours |
| Sitagliptin 200 mg | Time of Occurence of Maximum Concentration (Tmax) Following a Single Dose of Sitagliptin | 2.5 hours |