Diabetes Mellitus
Conditions
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus,, Lipoatrophic, Dyslipidemia, Drug Therapy
Brief summary
The purpose of this study is to evaluate the long-term safety of alogliptin, once daily (QD), following participation in 1 of 7 controlled studies in patients with type 2 diabetes mellitus.
Detailed description
SYR-322 (alogliptin) is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes mellitus by prolonging the beneficial effects of glucagon-like peptide-1. The rising incidence of type 2 diabetes mellitus and the limitations of the currently available treatments suggest the need for new therapies for glycemic control. Studies have been undertaken in humans that evaluated the effects of directly augmenting glucagon-like peptide-1 and glucose-dependent insulinotropic peptide levels and of inhibiting the activity of dipeptidyl peptidase IV. This study is an extension of 7 controlled phase 3 studies of alogliptin. These phase 3 studies included 1 monotherapy study of alogliptin (SYR-322-PLC-010; NCT00286455); 4 placebo-controlled add-on studies of alogliptin, namely in combination with a sulfonylurea (SYR-322-SULF-007; NCT00286468), metformin (SYR-322-MET-008; NCT00286442), a thiazolidinedione (pioglitazone; SYR-322-TZD-009; NCT00286494), and insulin (SYR-322-INS-011; NCT00286429); 1 coadministration study with pioglitazone in combination with metformin (01-05-TL-322OPI-001; NCT00328627), and 1 coadministration study with pioglitazone (01-06-TL-322OPI-002; NCT00395512). The end of treatment or early withdrawal visit from the preceding study will be the screening visit for this study, after which enrolled patients will be required to commit to approximately 22 additional visits at the study center.
Interventions
DRUGAlogliptin
Alogliptin tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. * Type 2 diabetes mellitus and was enrolled in one of the following 7 controlled Phase III studies. The study will be open to all patients who completed one of these studies through the end-of-treatment visit: * SYR-322-PLC-010 - NCT00286455 * SYR-322-SULF-007 - NCT00286468 * SYR-322-MET-008 - NCT00286442 * SYR-322-TZD-009 - NCT00286494 * SYR-322-INS-011 - NCT00286429 * 01-05-TL-322OPI-001 - NCT00328627 * 01-06-TL-322OPI-002 - NCT00395512 * Alanine aminotransferase less than or equal to 3 times the upper limit of normal and serum creatinine less than or equal to 2.0 mg per dL. * Able and willing to monitor own blood glucose concentrations with a home glucose monitor. * No major illness or debility that in the investigator's opinion prohibits the patient from completing the study.
Exclusion criteria
* The occurrence of any adverse event or condition during the controlled Phase III studies, which, in the opinion of the investigator, should exclude the patient from participating in the open-label extension. * Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including: * Weight-loss drugs * Investigational antidiabetics, additional dipeptidyl peptidase-4 (DPP-4) and glucagon-like peptide-1 (GLP 1) inhibitors * Incretin Mimetics, * Oral or systemically injected glucocorticoids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 years | Safety was assessed by physical examinations, clinical laboratory parameters, electrocardiogram (ECG) readings, vital sign measurements, oral temperature, and hypoglycemic events. Changes in laboratory values or ECG parameters were considered to be adverse events if they were judged to be clinically significant. A TEAE was any event that started on or after the first dose of open-label study drug and within 14 days after the last dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose | Baseline and Year 4 | The change from Baseline in fasting plasma glucose (FPG) at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug. |
| Percentage of Participants With Marked Hyperglycemia | Randomization up to 4 years. | Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (≥11.10 mmol/L). The Month 42 to Month 45 interval includes all marked hyperglycemic episodes occurring on or after Day 1247 (a 203-day visit window). |
| Change From Baseline in Proinsulin Level | Baseline and Year 4 | Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug. Note: A transcription error occurred in the reporting of 1 proinsulin value for a patient in the alogliptin 25 mg completed group, for whom a partial patient ID number was mistakenly entered as an end-of-treatment proinsulin level. |
| Change From Baseline Over Time in Glycosylated Hemoglobin | Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45. | The change from Baseline in glycosylated hemoglobin (HbA1c; the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Endpoint was defined as the last postbaseline observation collected within 7 days after the last dose of open-label study drug. |
| Change From Baseline in C-peptide Level | Baseline and Year 4 | C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug. |
| Change From Baseline in Body Weight | Baseline and Year 4 | Change from Baseline in body weight to the last post-baseline observation collected within 7 days after the last dose of open-label study drug. |
| Percentage of Participants With a Clinical Response | Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose. | Clinical response was defined based on the absolute value of HbA1c meeting one of two clinical targets at any post-baseline visit: * HbA1c ≤6.5%; * HbA1c ≤7.0%. |
| Change From Baseline in Insulin Level | Baseline and Year 4 | The change from Baseline in fasting insulin at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug. |
Countries
Argentina, Brazil, Chile, Czechia, Dominican Republic, Germany, Guatemala, Netherlands, Peru, Poland, South Africa, United States
Participant flow
Recruitment details
Patients who completed 1 of the following 7 studies took part in the study at 423 investigative sites worldwide: SYR-322-PLC-010 (NCT00286455); SYR-322-SULF-007 (NCT00286468); SYR-322-MET-008 (NCT00286442); SYR-322-TZD-009 (NCT00286494); SYR-322-INS-011 (NCT00286429); 01-05-TL-322OPI-001 (NCT00328627); 01-06-TL-322OPI-002 (NCT00395512).
Pre-assignment details
Patients who had previously completed 1 of 7 double-blind alogliptin studies were randomized (1:1) to either 12.5 or 25 mg once daily alogliptin. Patients who were rescued during their previous double-blind study in response to protocol-defined hyperglycemic rescue criteria were assigned to alogliptin 25 mg.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin 12.5 mg Participants who completed the previous double-blind study received alogliptin 12.5 tablet, orally, once daily for up to 4 years. | 1,396 |
| Alogliptin 25 mg Participants who completed the previous double-blind study received alogliptin 25 mg tablets orally, once daily for up to 4 years. | 1,399 |
| Rescued: Alogliptin 25 mg Participants rescued from the previous double-blind study received alogliptin 25 mg tablets, orally once daily for up to 4 years. | 528 |
| Total | 3,323 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 103 | 87 | 40 |
| Overall Study | Investigator discretion | 28 | 31 | 21 |
| Overall Study | Lack of Efficacy | 26 | 40 | 38 |
| Overall Study | Lost to Follow-up | 57 | 41 | 35 |
| Overall Study | Major protocol deviation | 43 | 51 | 18 |
| Overall Study | Other | 80 | 70 | 32 |
| Overall Study | Pregnancy | 3 | 1 | 1 |
| Overall Study | Site closure | 2 | 0 | 0 |
| Overall Study | Study termination | 1 | 0 | 1 |
| Overall Study | Voluntary withdrawal | 199 | 187 | 91 |
Baseline characteristics
| Characteristic | Alogliptin 12.5 mg | Alogliptin 25 mg | Rescued: Alogliptin 25 mg | Total |
|---|---|---|---|---|
| Age Continuous | 55.8 years STANDARD_DEVIATION 9.92 | 55.1 years STANDARD_DEVIATION 10.21 | 53.0 years STANDARD_DEVIATION 10.06 | 55.0 years STANDARD_DEVIATION 10.11 |
| Age, Customized <65 years | 1134 participants | 1134 participants | 461 participants | 2729 participants |
| Age, Customized ≥65 years | 262 participants | 265 participants | 67 participants | 594 participants |
| Body Mass Index (BMI) | 31.42 kg/m^2 STANDARD_DEVIATION 5.37 | 31.71 kg/m^2 STANDARD_DEVIATION 5.266 | 32.20 kg/m^2 STANDARD_DEVIATION 5.704 | 31.66 kg/m^2 STANDARD_DEVIATION 5.386 |
| Diabetes duration | 6.56 years STANDARD_DEVIATION 5.446 | 6.92 years STANDARD_DEVIATION 5.824 | 8.35 years STANDARD_DEVIATION 6.325 | 6.99 years STANDARD_DEVIATION 5.784 |
| Previous double-blind study treatment Alogliptin 12.5 mg | 274 participants | 262 participants | 105 participants | 641 participants |
| Previous double-blind study treatment Alogliptin 25 mg | 243 participants | 262 participants | 99 participants | 604 participants |
| Previous double-blind study treatment Placebo | 118 participants | 110 participants | 135 participants | 363 participants |
| Previous double-blind study treatment Study 01-05-TL-322OPI-001 | 546 participants | 548 participants | 146 participants | 1240 participants |
| Previous double-blind study treatment Study 01-06-TL-322OPI-002 | 215 participants | 217 participants | 43 participants | 475 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 8 participants | 3 participants | 2 participants | 13 participants |
| Race/Ethnicity, Customized Asian | 120 participants | 108 participants | 32 participants | 260 participants |
| Race/Ethnicity, Customized Black or African American | 65 participants | 88 participants | 34 participants | 187 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 participants | 0 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Other | 176 participants | 193 participants | 69 participants | 438 participants |
| Race/Ethnicity, Customized White | 1025 participants | 1007 participants | 390 participants | 2422 participants |
| Sex: Female, Male Female | 699 Participants | 730 Participants | 289 Participants | 1718 Participants |
| Sex: Female, Male Male | 697 Participants | 669 Participants | 239 Participants | 1605 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 876 / 1,394 | 898 / 1,399 | 333 / 527 |
| serious Total, serious adverse events | 233 / 1,394 | 228 / 1,399 | 83 / 527 |
Outcome results
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Safety was assessed by physical examinations, clinical laboratory parameters, electrocardiogram (ECG) readings, vital sign measurements, oral temperature, and hypoglycemic events. Changes in laboratory values or ECG parameters were considered to be adverse events if they were judged to be clinically significant. A TEAE was any event that started on or after the first dose of open-label study drug and within 14 days after the last dose.
Time frame: 4 years
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 12.5 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Study drug-related serious AE | 2.6 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation | 7.0 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-emergent deaths | 1.4 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 87.2 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment emergent serious AE | 16.7 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Study drug-related TEAE | 25.6 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment emergent serious AE | 16.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Study drug-related serious AE | 2.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Study drug-related TEAE | 22.7 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-emergent deaths | 1.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 87.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation | 6.1 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-emergent deaths | 0.9 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 84.6 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Study drug-related TEAE | 24.9 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation | 7.6 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment emergent serious AE | 15.7 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Study drug-related serious AE | 1.9 percentage of participants |
Secondary
Change From Baseline in Body Weight
Change from Baseline in body weight to the last post-baseline observation collected within 7 days after the last dose of open-label study drug.
Time frame: Baseline and Year 4
Population: Safety set for whom data was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 12.5 mg | Change From Baseline in Body Weight | Baseline | 86.12 kg | Standard Deviation 19.376 |
| Alogliptin 12.5 mg | Change From Baseline in Body Weight | Change from Baseline | -0.64 kg | Standard Deviation 5.283 |
| Alogliptin 25 mg | Change From Baseline in Body Weight | Baseline | 86.61 kg | Standard Deviation 19.185 |
| Alogliptin 25 mg | Change From Baseline in Body Weight | Change from Baseline | -0.61 kg | Standard Deviation 5.428 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Body Weight | Baseline | 88.62 kg | Standard Deviation 20.947 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Body Weight | Change from Baseline | 0.25 kg | Standard Deviation 5.036 |
Secondary
Change From Baseline in C-peptide Level
C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Time frame: Baseline and Year 4
Population: Safety set where data was available. Patients enrolled in Protocol 01-05-TL-OPI322-001 or Protocol 01-06-TL-OPI322-002 are not included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 12.5 mg | Change From Baseline in C-peptide Level | Baseline | 3.406 ng/mL | Standard Deviation 1.5115 |
| Alogliptin 12.5 mg | Change From Baseline in C-peptide Level | Change from Baseline | -0.471 ng/mL | Standard Deviation 1.6464 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Level | Baseline | 3.323 ng/mL | Standard Deviation 1.5945 |
| Alogliptin 25 mg | Change From Baseline in C-peptide Level | Change from Baseline | -0.439 ng/mL | Standard Deviation 1.2783 |
| Rescued: Alogliptin 25 mg | Change From Baseline in C-peptide Level | Baseline | 3.572 ng/mL | Standard Deviation 1.7531 |
| Rescued: Alogliptin 25 mg | Change From Baseline in C-peptide Level | Change from Baseline | -0.641 ng/mL | Standard Deviation 1.5804 |
Secondary
Change From Baseline in Fasting Plasma Glucose
The change from Baseline in fasting plasma glucose (FPG) at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Time frame: Baseline and Year 4
Population: Safety set where data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 12.5 mg | Change From Baseline in Fasting Plasma Glucose | Baseline | 144.4 mg/dL | Standard Deviation 41.64 |
| Alogliptin 12.5 mg | Change From Baseline in Fasting Plasma Glucose | Change from Baseline | 14.8 mg/dL | Standard Deviation 56.25 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | Baseline | 142.6 mg/dL | Standard Deviation 39.41 |
| Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | Change from Baseline | 14.9 mg/dL | Standard Deviation 53.46 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | Baseline | 215.3 mg/dL | Standard Deviation 60.25 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Fasting Plasma Glucose | Change from Baseline | -26.4 mg/dL | Standard Deviation 84.51 |
Secondary
Change From Baseline in Insulin Level
The change from Baseline in fasting insulin at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Time frame: Baseline and Year 4
Population: Safety set where data was available. Does not include patients enrolled in Protocol 01-05-TL-OPI322-001 or Protocol 01-06-TL-OPI322-002.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 12.5 mg | Change From Baseline in Insulin Level | Baseline | 15.19 μIU/mL | Standard Deviation 9.898 |
| Alogliptin 12.5 mg | Change From Baseline in Insulin Level | Change from Baseline | 2.45 μIU/mL | Standard Deviation 42.706 |
| Alogliptin 25 mg | Change From Baseline in Insulin Level | Baseline | 15.50 μIU/mL | Standard Deviation 12.608 |
| Alogliptin 25 mg | Change From Baseline in Insulin Level | Change from Baseline | 2.13 μIU/mL | Standard Deviation 16.496 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Insulin Level | Baseline | 18.64 μIU/mL | Standard Deviation 15.845 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Insulin Level | Change from Baseline | 5.62 μIU/mL | Standard Deviation 23.197 |
Secondary
Change From Baseline in Proinsulin Level
Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug. Note: A transcription error occurred in the reporting of 1 proinsulin value for a patient in the alogliptin 25 mg completed group, for whom a partial patient ID number was mistakenly entered as an end-of-treatment proinsulin level.
Time frame: Baseline and Year 4
Population: Safety set where data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 12.5 mg | Change From Baseline in Proinsulin Level | Baseline | 26.1 pmol/L | Standard Deviation 25.99 |
| Alogliptin 12.5 mg | Change From Baseline in Proinsulin Level | Change from Baseline | 4.1 pmol/L | Standard Deviation 27.09 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin Level | Baseline | 25.4 pmol/L | Standard Deviation 30.28 |
| Alogliptin 25 mg | Change From Baseline in Proinsulin Level | Change from Baseline | 39.7 pmol/L | Standard Deviation 1243.37 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Proinsulin Level | Baseline | 40.2 pmol/L | Standard Deviation 36.47 |
| Rescued: Alogliptin 25 mg | Change From Baseline in Proinsulin Level | Change from Baseline | -3.3 pmol/L | Standard Deviation 31.45 |
Secondary
Change From Baseline Over Time in Glycosylated Hemoglobin
The change from Baseline in glycosylated hemoglobin (HbA1c; the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Endpoint was defined as the last postbaseline observation collected within 7 days after the last dose of open-label study drug.
Time frame: Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45.
Population: Safety set where data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 33 change from Baseline (n=923, 941, 276) | 0.55 percent glycosylated hemoglobin | Standard Deviation 1.181 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 18 change from Baseline (n=1111, 1095, 350) | 0.50 percent glycosylated hemoglobin | Standard Deviation 1.082 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Week 12 change from Baseline (n=1290, 1286, 463) | 0.18 percent glycosylated hemoglobin | Standard Deviation 0.635 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Baseline (n=1362, 1359, 501) | 7.21 percent glycosylated hemoglobin | Standard Deviation 0.815 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 21 change from Baseline (n=1061, 1071, 338) | 0.52 percent glycosylated hemoglobin | Standard Deviation 1.096 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 42 change from Baseline (n=854, 891, 252) | 0.59 percent glycosylated hemoglobin | Standard Deviation 1.225 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 30 change from Baseline (n=944, 955, 281) | 0.57 percent glycosylated hemoglobin | Standard Deviation 1.127 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 24 change from Baseline (n=1027, 1039, 320) | 0.53 percent glycosylated hemoglobin | Standard Deviation 1.111 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 9 change from Baseline (n=1217, 1231, 413) | 0.34 percent glycosylated hemoglobin | Standard Deviation 0.969 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 27 change from Baseline (n=991, 1002, 300) | 0.58 percent glycosylated hemoglobin | Standard Deviation 1.124 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Endpoint change from Baseline (n=1362, 1359, 501) | 1.63 percent glycosylated hemoglobin | Standard Deviation 1.31 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 39 change from Baseline (n=886, 913, 259) | 0.56 percent glycosylated hemoglobin | Standard Deviation 1.223 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 12 change from Baseline (1175, 1182, 388) | 0.41 percent glycosylated hemoglobin | Standard Deviation 1.01 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 45 change from Baseline (n=866, 902, 253) | 0.61 percent glycosylated hemoglobin | Standard Deviation 1.25 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 36 change from Baseline (n=882, 931, 274) | 0.54 percent glycosylated hemoglobin | Standard Deviation 1.215 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 15 change from Baseline (n=1119, 1133, 374) | 0.47 percent glycosylated hemoglobin | Standard Deviation 0.99 |
| Alogliptin 12.5 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 6 change from Baseline (n= 1236, 1252, 433) | 0.31 percent glycosylated hemoglobin | Standard Deviation 0.859 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 30 change from Baseline (n=944, 955, 281) | 0.57 percent glycosylated hemoglobin | Standard Deviation 1.167 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Baseline (n=1362, 1359, 501) | 7.22 percent glycosylated hemoglobin | Standard Deviation 0.814 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Week 12 change from Baseline (n=1290, 1286, 463) | 0.14 percent glycosylated hemoglobin | Standard Deviation 0.632 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 6 change from Baseline (n= 1236, 1252, 433) | 0.26 percent glycosylated hemoglobin | Standard Deviation 0.848 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 9 change from Baseline (n=1217, 1231, 413) | 0.33 percent glycosylated hemoglobin | Standard Deviation 0.894 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 12 change from Baseline (1175, 1182, 388) | 0.41 percent glycosylated hemoglobin | Standard Deviation 0.952 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 15 change from Baseline (n=1119, 1133, 374) | 0.48 percent glycosylated hemoglobin | Standard Deviation 1.068 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 18 change from Baseline (n=1111, 1095, 350) | 0.50 percent glycosylated hemoglobin | Standard Deviation 1.047 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 21 change from Baseline (n=1061, 1071, 338) | 0.51 percent glycosylated hemoglobin | Standard Deviation 1.07 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 24 change from Baseline (n=1027, 1039, 320) | 0.58 percent glycosylated hemoglobin | Standard Deviation 1.107 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 27 change from Baseline (n=991, 1002, 300) | 0.58 percent glycosylated hemoglobin | Standard Deviation 1.159 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 33 change from Baseline (n=923, 941, 276) | 0.57 percent glycosylated hemoglobin | Standard Deviation 1.196 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 36 change from Baseline (n=882, 931, 274) | 0.55 percent glycosylated hemoglobin | Standard Deviation 1.141 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 39 change from Baseline (n=886, 913, 259) | 0.56 percent glycosylated hemoglobin | Standard Deviation 1.216 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 42 change from Baseline (n=854, 891, 252) | 0.54 percent glycosylated hemoglobin | Standard Deviation 1.221 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 45 change from Baseline (n=866, 902, 253) | 0.56 percent glycosylated hemoglobin | Standard Deviation 1.242 |
| Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Endpoint change from Baseline (n=1362, 1359, 501) | 0.61 percent glycosylated hemoglobin | Standard Deviation 1.261 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Week 12 change from Baseline (n=1290, 1286, 463) | -0.52 percent glycosylated hemoglobin | Standard Deviation 1.064 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 33 change from Baseline (n=923, 941, 276) | -0.73 percent glycosylated hemoglobin | Standard Deviation 1.418 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 12 change from Baseline (1175, 1182, 388) | -0.78 percent glycosylated hemoglobin | Standard Deviation 1.309 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Endpoint change from Baseline (n=1362, 1359, 501) | -0.42 percent glycosylated hemoglobin | Standard Deviation 1.448 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 36 change from Baseline (n=882, 931, 274) | -0.80 percent glycosylated hemoglobin | Standard Deviation 1.411 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 9 change from Baseline (n=1217, 1231, 413) | -0.78 percent glycosylated hemoglobin | Standard Deviation 1.282 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 45 change from Baseline (n=866, 902, 253) | -0.70 percent glycosylated hemoglobin | Standard Deviation 1.398 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 39 change from Baseline (n=886, 913, 259) | -0.73 percent glycosylated hemoglobin | Standard Deviation 1.431 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 6 change from Baseline (n= 1236, 1252, 433) | -0.73 percent glycosylated hemoglobin | Standard Deviation 1.285 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Baseline (n=1362, 1359, 501) | 9.30 percent glycosylated hemoglobin | Standard Deviation 0.9 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 24 change from Baseline (n=1027, 1039, 320) | -0.69 percent glycosylated hemoglobin | Standard Deviation 1.417 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 42 change from Baseline (n=854, 891, 252) | -0.78 percent glycosylated hemoglobin | Standard Deviation 1.492 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 27 change from Baseline (n=991, 1002, 300) | -0.71 percent glycosylated hemoglobin | Standard Deviation 1.349 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 21 change from Baseline (n=1061, 1071, 338) | -0.75 percent glycosylated hemoglobin | Standard Deviation 1.389 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 18 change from Baseline (n=1111, 1095, 350) | -0.70 percent glycosylated hemoglobin | Standard Deviation 1.32 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 30 change from Baseline (n=944, 955, 281) | -0.78 percent glycosylated hemoglobin | Standard Deviation 1.361 |
| Rescued: Alogliptin 25 mg | Change From Baseline Over Time in Glycosylated Hemoglobin | Month 15 change from Baseline (n=1119, 1133, 374) | -0.75 percent glycosylated hemoglobin | Standard Deviation 1.332 |
Secondary
Percentage of Participants With a Clinical Response
Clinical response was defined based on the absolute value of HbA1c meeting one of two clinical targets at any post-baseline visit: * HbA1c ≤6.5%; * HbA1c ≤7.0%.
Time frame: Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose.
Population: Safety set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 12.5 mg | Percentage of Participants With a Clinical Response | HbA1c ≤6.5% | 34.8 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With a Clinical Response | HbA1c ≤7.0% | 64.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With a Clinical Response | HbA1c ≤6.5% | 34.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With a Clinical Response | HbA1c ≤7.0% | 65.5 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With a Clinical Response | HbA1c ≤6.5% | 11.0 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With a Clinical Response | HbA1c ≤7.0% | 27.1 percentage of participants |
Secondary
Percentage of Participants With Marked Hyperglycemia
Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (≥11.10 mmol/L). The Month 42 to Month 45 interval includes all marked hyperglycemic episodes occurring on or after Day 1247 (a 203-day visit window).
Time frame: Randomization up to 4 years.
Population: Safety set where data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 9 to <Month 12 (n=1252, 1260, 425) | 11.4 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to <Week 8 (n=1303, 1331, 490) | 9.2 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 30 to <Month 33 (n=981, 988, 299) | 11.6 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 12 to <Month 15 (n=1210, 1217, 409) | 13.1 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n= 1389, 1392, 518) | 49.7 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 27 to <Month 30 (n=1010, 1028, 316) | 12.6 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 15 to <Month 18 (n=1157, 1166, 389) | 12.7 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 18 to <Month 21 (n=1128, 1128, 365) | 11.7 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 24 to <Month 27 (n=1046, 1066, 334) | 11.6 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to <Week 12 (n=1331, 1347, 495) | 11.5 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 21 to <Month 24 (n=1094,1099, 357) | 11.2 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Week 2 to <Week 4 (n=1286, 1306, 481) | 11.5 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 39 to <Month 42 (n=899, 934, 267) | 13.7 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to <Month 6 (n=1329, 1338, 480) | 12.0 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Day 1 to <Week 2 (n=1299, 1290, 481) | 9.1 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 36 to <Month 39 (n=920, 949, 281) | 13.2 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 6 to <Month 9 (n=1286, 1289, 448) | 12.8 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 42 to Month 45 (n=889, 921, 261) | 25.5 percentage of participants |
| Alogliptin 12.5 mg | Percentage of Participants With Marked Hyperglycemia | Month 33 to <Month 36 (n=945, 959, 289) | 11.5 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 39 to <Month 42 (n=899, 934, 267) | 13.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Day 1 to <Week 2 (n=1299, 1290, 481) | 8.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 2 to <Week 4 (n=1286, 1306, 481) | 10.2 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to <Week 8 (n=1303, 1331, 490) | 11.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to <Week 12 (n=1331, 1347, 495) | 10.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to <Month 6 (n=1329, 1338, 480) | 11.6 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 6 to <Month 9 (n=1286, 1289, 448) | 10.7 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 9 to <Month 12 (n=1252, 1260, 425) | 12.9 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 12 to <Month 15 (n=1210, 1217, 409) | 13.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 15 to <Month 18 (n=1157, 1166, 389) | 13.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 18 to <Month 21 (n=1128, 1128, 365) | 11.6 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 21 to <Month 24 (n=1094,1099, 357) | 11.5 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 24 to <Month 27 (n=1046, 1066, 334) | 12.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 27 to <Month 30 (n=1010, 1028, 316) | 11.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 30 to <Month 33 (n=981, 988, 299) | 11.7 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 33 to <Month 36 (n=945, 959, 289) | 12.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 36 to <Month 39 (n=920, 949, 281) | 12.5 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 42 to Month 45 (n=889, 921, 261) | 23.9 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n= 1389, 1392, 518) | 50.7 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 27 to <Month 30 (n=1010, 1028, 316) | 24.7 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 9 to <Month 12 (n=1252, 1260, 425) | 32.5 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Overall (n= 1389, 1392, 518) | 87.6 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 30 to <Month 33 (n=981, 988, 299) | 19.7 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 6 to <Month 9 (n=1286, 1289, 448) | 36.8 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 42 to Month 45 (n=889, 921, 261) | 39.1 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 33 to <Month 36 (n=945, 959, 289) | 23.5 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 12 to <Month 6 (n=1329, 1338, 480) | 39.4 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Day 1 to <Week 2 (n=1299, 1290, 481) | 55.5 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 36 to <Month 39 (n=920, 949, 281) | 21.0 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 8 to <Week 12 (n=1331, 1347, 495) | 41.0 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 18 to <Month 21 (n=1128, 1128, 365) | 26.8 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 4 to <Week 8 (n=1303, 1331, 490) | 46.1 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 21 to <Month 24 (n=1094,1099, 357) | 26.3 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 15 to <Month 18 (n=1157, 1166, 389) | 27.8 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 39 to <Month 42 (n=899, 934, 267) | 19.5 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 24 to <Month 27 (n=1046, 1066, 334) | 24.9 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Month 12 to <Month 15 (n=1210, 1217, 409) | 29.3 percentage of participants |
| Rescued: Alogliptin 25 mg | Percentage of Participants With Marked Hyperglycemia | Week 2 to <Week 4 (n=1286, 1306, 481) | 45.9 percentage of participants |