Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to evaluate the pharmacokinetics of Saxagliptin, 5-hydroxy Saxagliptin, and Metformin in pediatric subjects with Type 2 diabetes mellitus (T2DM) following oral administration of Saxagliptin and Metformin XR fixed dose combination tablet and co-administration of Saxagliptin and Glucophage® (Metformin) IR tablets
Detailed description
The primary purpose is to assess the pharmacokinetics of Saxagliptin, 5-hydroxy Saxagliptin, and Metformin in pediatric subjects aged 10 to 17 years with T2DM following oral administration of Saxagliptin and Metformin XR fixed dose combination tablet and co-administration of Saxagliptin and Glucophage® (Metformin) IR tablets
Interventions
Tablet, Oral, 1000 mg, twice daily, 1 day
DRUGSaxagliptin
Tablet, Oral, 5 mg, single-dose, 1 day
DRUGMetformin IR
Tablet, Oral, 1000 mg, twice daily, 5 days
Tablet, Oral, 2.5 mg Saxagliptin/1000 mg Metformin extended release (XR), Single-dose of 2 tablets. Fixed dose combination (FDC).
DRUGMetformin XR
Tablet, Oral, 500 mg, Single-dose of 4 tablets
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of T2DM * Male and female subjects ages 10-17 * Body weight ≥50 kg * Glycosylated hemoglobin (HbA1c) 6.5 to 10%
Exclusion criteria
* Fasting plasma glucose (FPG) \> 240 mg/dL at screening * Abnormal renal function * Active liver disease and/or significant abnormal liver function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | Day 1 up to Day 8, plus 30 days | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Marked Chemistry or Hematology Laboratory Abnormalities | Day 1 to Day 8 | Lower limit of normal (LLN); upper limit of normal (ULN); treatment (RX); pre-treatment (Pre-Rx); units per liter (U/L); millimoles per liter (mmol/L). Alkaline phosphatase U/L:\>1.25\*Pre-RX if Pre-RX \>ULN or \>1.25\*ULN if Pre-RX \<=ULN; aspartate aminotransferase U/L: \>1.25\*Pre-RX if Pre-RX\>ULN or 1.25\*ULN if Pre-RX\<=ULN;alanine aminotransferase U/L: \>1.25\*Pre-RX if Pre-RX\>ULN or 1.25\*ULN if Pre-RX\<=ULN;blood urea nitrogen mmol/L: \>1.1\*ULN if Pre-RX \<=ULN or \>1.2\*Pre-RX if Pre-RX \>ULN; total bilirubin µmol/L: \>1.1\*ULN if Pre-RX \<=ULN or \>1.25\*Pre-RX if Pre-RX \>ULN; creatine phosphokinase U/L: \>1.5\*Pre-RX if Pre-RX\>ULN or \>1.5\*ULN if Pre-RX \<= ULN. Grams per liter (g/L); cells per liter (c/L). Hemoglobin (g/L): \<0.85\* pre-RX; hematocrit (%): \<0.85\*pre-RX;erythrocytes (\*10\^12 c/L): \<0.85\*pre-RX; platelet count (\*10\^9 c/L): \<0.85\*LLN if pre-RX\>=LLN, or if Pre-Tx \<LLN; leukocytes (\*10\^9 c/L): \<0.85\*LLN if pre-RX \<LLN,or \<0.9\*LLN if LLN\<=Pre-RX\<=ULN. |
Countries
United States
Participant flow
Recruitment details
Upon approval of Kombiglyze™ XR, the Food and Drug Administration (FDA) required the conduct of this clinical pharmacology study in pediatric patients as a post-marketing requirement (PMR). Study was initiated February 2013. On 14-Nov-13, the FDA issued a letter stating release from this PMR, thus the study was terminated prior to completion.
Pre-assignment details
A total of 4 participants were enrolled. Two participants were treated and completed the study prior to the termination of the study.
Participants by arm
| Arm | Count |
|---|---|
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® IR tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin XR FDC tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Enrollment | No longer met study criteria | 1 |
| Enrollment | Other | 1 |
Baseline characteristics
| Characteristic | Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC |
|---|---|
| Age, Continuous | 13.0 years |
| Race/Ethnicity, Customized Black/African American | 1 participants |
| Race/Ethnicity, Customized White | 1 participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time frame: Day 1 up to Day 8, plus 30 days
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC | Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | AE | 2 participants |
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC | Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | Treatment-Related AE | 1 participants |
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC | Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | AE Leading to Discontinuation | 0 participants |
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC | Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | SAE | 0 participants |
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC | Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | Death | 0 participants |
Secondary
Number of Participants With Marked Chemistry or Hematology Laboratory Abnormalities
Lower limit of normal (LLN); upper limit of normal (ULN); treatment (RX); pre-treatment (Pre-Rx); units per liter (U/L); millimoles per liter (mmol/L). Alkaline phosphatase U/L:\>1.25\*Pre-RX if Pre-RX \>ULN or \>1.25\*ULN if Pre-RX \<=ULN; aspartate aminotransferase U/L: \>1.25\*Pre-RX if Pre-RX\>ULN or 1.25\*ULN if Pre-RX\<=ULN;alanine aminotransferase U/L: \>1.25\*Pre-RX if Pre-RX\>ULN or 1.25\*ULN if Pre-RX\<=ULN;blood urea nitrogen mmol/L: \>1.1\*ULN if Pre-RX \<=ULN or \>1.2\*Pre-RX if Pre-RX \>ULN; total bilirubin µmol/L: \>1.1\*ULN if Pre-RX \<=ULN or \>1.25\*Pre-RX if Pre-RX \>ULN; creatine phosphokinase U/L: \>1.5\*Pre-RX if Pre-RX\>ULN or \>1.5\*ULN if Pre-RX \<= ULN. Grams per liter (g/L); cells per liter (c/L). Hemoglobin (g/L): \<0.85\* pre-RX; hematocrit (%): \<0.85\*pre-RX;erythrocytes (\*10\^12 c/L): \<0.85\*pre-RX; platelet count (\*10\^9 c/L): \<0.85\*LLN if pre-RX\>=LLN, or if Pre-Tx \<LLN; leukocytes (\*10\^9 c/L): \<0.85\*LLN if pre-RX \<LLN,or \<0.9\*LLN if LLN\<=Pre-RX\<=ULN.
Time frame: Day 1 to Day 8
Population: Participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC | Number of Participants With Marked Chemistry or Hematology Laboratory Abnormalities | 0 participants |