Diabetes Mellitus, Type 2
Conditions
Keywords
Drug Therapy
Brief summary
The primary purpose of this study is to evaluate the efficacy of alogliptin 25 milligram (mg) once daily compared to placebo when administered as monotherapy, or when added onto a background of metformin alone, insulin alone, or a combination of metformin and insulin, as measured by the glycosylated hemoglobin (HbA1c) change from Baseline at Week 26 in pediatric participants with type 2 diabetes mellitus (T2DM).
Detailed description
The drug being tested in this study is called alogliptin. Alogliptin is being tested to treat children 10 to 17 years of age who have T2DM and are experiencing inadequate glycemic control. This study will look at HbA1c fluctuations in children who take alogliptin in addition to their background antidiabetic therapy. The study will enroll approximately 150 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Alogliptin 25 mg * Placebo (dummy inactive pill) - this is a tablet that looks like the tablet containing alogliptin 25 mg but has no active ingredient (that is, has no alogliptin). All participants will be asked to take one tablet at the same time each day throughout the study in addition to their current background antidiabetic therapy (metformin and/or insulin) if applicable. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 56 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 2 weeks after the last dose of study drug for a follow-up assessment.
Interventions
Alogliptin benzoate tablets.
DRUGPlacebo
Alogliptin placebo-matching tablets.
Sponsors
Takeda Development Center Americas, Inc.
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Has a confirmed diagnosis of T2DM using American Diabetes Association (ADA) and World Health Organization (WHO) criteria (laboratory determinations of fasting plasma glucose \[FPG\] greater than or equal to \[\>=\] 126 mg/dL, random glucose \>=200 mg/dL \[\>=11.10 mmol/L\], HbA1c \>=6.5 percent (%), or 2-hour oral glucose tolerance test \[OGTT\] glucose \>=200 mg/dL), documented in the participants' medical record. 2. The participant and/or his/her legal representative (that is, parents or legal guardians) are able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete participant diaries.
Exclusion criteria
1. Has a history of hypersensitivity or allergy to alogliptin, other dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, insulin or related compounds. 2. Has a confirmed diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY). 3. Has a hemoglobin level \<11.0 gram per deciliter (g/dL) (\<110 gram per liter \[g/L\]) for males and \<10.0 g/dL (\<100 g/L) for females. 4. Has a history of any hemoglobinopathy that may affect determination of HbA1c levels. 5. Has a history of bariatric surgery. 6. Has a history of proliferative diabetic retinopathy within the 6 months prior to Screening. 7. Has had more than 1 episode of diabetic ketoacidosis (DKA) at any time after diagnosis of T2DM. 8. Has a history of more than 1 episode of pancreatitis. 9. Has serum creatinine \>=1.5 mg/dL for male participants or \>=1.4 mg/dL for female participants, or creatinine clearance \<60 milliliter per minute (mL/min) based on calculation by central lab using the Schwartz formula for estimated glomerular filtration rate (eGFR) at screening Visit. 10. Has a documented history of infection with human immunodeficiency virus or chronic active viral hepatitis. 11. The participant and/or his/her legal representative (that is, parents or legal guardians) is unable to understand verbal or written English, or any other language for which a certified translation of the approved informed consent/assent is available. Additional Criteria That Must be Met Prior to Randomization: For participants who have had the diagnosis of T2DM for less than 1 year and/or who are taking insulin at Screening, additional criteria will need to be met prior to randomization: 1. Must have an HbA1c level of \>=6.5% to \<11.0% if the participant is treatment naïve or on metformin alone or \>=7.0% to \<11.0% if the participant is on insulin alone or in combination with metformin. 2. The participant must not have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to randomization. 3. Must not have received an antidiabetic agent other than metformin or insulin within the 12 weeks prior to randomization. 4. Must not have received oral or parenteral steroids for more than 3 weeks (cumulatively) within the 6 months prior to randomization or have received a course of oral or parenteral steroids within the 2 months prior to randomization. 5. Has a systolic blood pressure \<160 millimeter of mercury (mmHg) and a diastolic pressure \<100 mm Hg. (Antihypertensive medications will be allowed during the study). 6. Has an alanine aminotransferase (ALT) level \<3\*upper limit of normal (ULN) or an ALT level \<5 \*ULN with a confirmed diagnosis of nonalcoholic fatty liver disease (NAFLD).7. Does not plan to leave the geographic area within 1 calendar year following randomization. For participants who have had the diagnosis of T2DM for less than 1 year and/or who are taking insulin prior to randomization, the following criteria must also be met: 8\. Must have a fasting C-peptide concentration\>=0.6 nanogram per milliliter (ng/mL) (\>=0.20 nanomole per liter \[nmol/L\]) (drawn at least 1 week after treatment for ketosis or acidosis, if applicable). 9\. No presence of autoantibodies as documented by glutamic acid decarboxylase \[GAD\] 65 and islet antigen \[IA\]-2 antibodies below the upper limit of the normal reference ranges at randomization. 10\. Have a body mass index (BMI) greater than (\>) 85th percentile, documented at randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | Baseline and Week 26 | Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Week 26 relative to Baseline. Mixed model for repeated measures (MMRM) was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinically Significant Physical Examination Findings | From Day 1 to end of treatment period (up to 52 weeks) | Physical examination included examination of the following body systems: (1) respiratory system; (2) cardiovascular system; (3) nervous system (4) dermatologic system; and (5) gastrointestinal system. A summarized data for the above body systems was reported for participants with clinically significant findings. |
| Percentage of Participants With Abnormal Vital Signs Values | From Day 1 to end of treatment period (up to 52 weeks) | Vital signs included body temperature (oral or tympanic measurement), respiratory rate, blood pressure \[systolic blood pressure (SBP) and diastolic blood pressure (DBP)\] resting more than 5 minutes, and pulse (beats per minute). Data for participants with abnormal vital signs was reported. The percentage of participants are calculated based on the participants with non-missing data at that time-point. |
| Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 26 and 52 | — |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | From the study start up to end of the study (up to 54 weeks) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. |
| Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | From Day 1 to end of treatment period (up to 52 weeks) | The percentage of participants are calculated based on the participants with non-missing data at that time-point. |
| Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Baseline and Weeks 12, 18, 39 and 52 | Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Weeks 12, 18, 39 and 52 relative to Baseline. MMRM was used for the analysis. |
| Percentage of Participants With Abnormal Safety Laboratory Findings | From Day 1 to end of treatment period (up to 52 weeks) | The percentage of participants with any abnormal standard safety laboratory values (hematology, serum chemistry, and urinalysis) were collected throughout study. Abnormal values for hematology included hematocrit (percentage of hematocrit \[%\]), hemoglobin (grams per liter \[g/L\]), erythrocyte mean corpuscular volume (MCV)(femtoliter \[fL\]), erythrocytes (10\^12/L), and leukocytes (10\^9/L). Abnormal values for serum chemistry included for alanine aminotransferase (units per liter \[U/L\]), aspartate aminotransferase (U/L), cholesterol (millimoles per liter \[mmol/L\]), gamma glutamyl transferase (U/L), glucose (mmol/L): \< 2.8 mmol/L, potassium (mmol/L), sodium (mmol/L), and triglycerides (mmol/L). ULN is upper limit of normal and LLN is lower limit of normal. |
| Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Baseline, Weeks 26 and 52 | Biomarkers of bone turnover are bone-specific alkaline phosphatase to assess changes in bone formation and C-terminal telopeptide (CTX) to assess changes in bone resorption. |
| Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Baseline, Weeks 26 and 52 | — |
| Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Baseline, Weeks 26 and 52 | — |
| Percentage of Participants With Hypoglycemia | From Day 1 to end of treatment period (up to 52 weeks) | Mild to moderate hypoglycemia (abnormal low blood sugar) was defined as blood glucose less than (\<) 60 milligram per deciliter (mg/dL) (3.33 millimole per liter \[mmol/L\]) in the presence of symptoms, or blood glucose \<50 mg/dL (2.78 mmol/L) with or without symptoms. Severe hypoglycemia was defined as any episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, associated with a documented blood glucose \<60 mg/dL (3.33 mmol/L) (unless the clinical situation makes obtaining a blood glucose difficult \[example, it involves coma or seizure\]). |
Countries
Brazil, Israel, Italy, Mexico, Poland, Russia, United States
Participant flow
Recruitment details
A total of 152 participants took part in the study at 67 investigative sites in Mexico, United States, Brazil, Israel, Italy and Russia from 14 October 2016 to 14 February 2022.
Pre-assignment details
Participants with type 2 diabetes mellitus were enrolled to receive placebo or alogliptin 25 mg in a 1:1 ratio in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Alogliptin matching-placebo tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period. | 76 |
| Alogliptin 25 mg Alogliptin 25 mg tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period. | 75 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not Complete Study but Contacted at Week 52 | 0 | 3 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Pretreatment Event/Adverse Event | 1 | 0 |
| Overall Study | Principal Investigator Discretion | 2 | 1 |
| Overall Study | Randomized but not Treated | 1 | 0 |
| Overall Study | Significant Protocol Deviation | 1 | 0 |
| Overall Study | Voluntary Withdrawal | 3 | 5 |
Baseline characteristics
| Characteristic | Alogliptin 25 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 1.92 | 14.2 years STANDARD_DEVIATION 2.06 | 14.3 years STANDARD_DEVIATION 2.21 |
| Baseline of Glycosylated Hemoglobin (HbA1c) | 8.16 percentage of HbA1c | 8.13 percentage of HbA1c | 8.11 percentage of HbA1c |
| Body Mass Index (BMI) | 33.669 kg/m^2 STANDARD_DEVIATION 8.6592 | 33.650 kg/m^2 STANDARD_DEVIATION 8.2381 | 33.632 kg/m^2 STANDARD_DEVIATION 7.8581 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 15 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 57 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 40 Participants | 79 Participants | 39 Participants |
| Height | 163.1 centimetres (cm) STANDARD_DEVIATION 8.79 | 163.9 centimetres (cm) STANDARD_DEVIATION 9.18 | 164.7 centimetres (cm) STANDARD_DEVIATION 9.54 |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 25 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 32 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 88 Participants | 44 Participants |
| Sex: Female, Male Female | 53 Participants | 104 Participants | 51 Participants |
| Sex: Female, Male Male | 22 Participants | 47 Participants | 25 Participants |
| Weight | 90.72 kilograms (kg) STANDARD_DEVIATION 28.815 | 91.48 kilograms (kg) STANDARD_DEVIATION 27.749 | 92.23 kilograms (kg) STANDARD_DEVIATION 26.826 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 75 |
| other Total, other adverse events | 39 / 76 | 31 / 75 |
| serious Total, serious adverse events | 3 / 76 | 2 / 75 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Week 26 relative to Baseline. Mixed model for repeated measures (MMRM) was used for the analysis.
Time frame: Baseline and Week 26
Population: FAS included all randomized participants in the safety set. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -0.011 percentage of HbA1c | Standard Deviation 0.2809 |
| Alogliptin 25 mg | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | 0.091 percentage of HbA1c | Standard Deviation 0.2879 |
p-value: =0.78295% CI: [-0.627, 0.831]MMRM
Secondary
Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52
Biomarkers of bone turnover are bone-specific alkaline phosphatase to assess changes in bone formation and C-terminal telopeptide (CTX) to assess changes in bone resorption.
Time frame: Baseline, Weeks 26 and 52
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed is the number of participants available for analysis at the specific time point. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Baseline | 62.09 units per liter (U/L) | Standard Deviation 37.084 |
| Placebo | Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Change From Baseline at Week 26 | -6.20 units per liter (U/L) | Standard Deviation 18.021 |
| Placebo | Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Change From Baseline at Week 52 | -14.36 units per liter (U/L) | Standard Deviation 18 |
| Alogliptin 25 mg | Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Baseline | 62.62 units per liter (U/L) | Standard Deviation 43.18 |
| Alogliptin 25 mg | Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Change From Baseline at Week 26 | -7.47 units per liter (U/L) | Standard Deviation 20.139 |
| Alogliptin 25 mg | Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Change From Baseline at Week 52 | -15.43 units per liter (U/L) | Standard Deviation 22.497 |
Secondary
Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52
Time frame: Baseline, Weeks 26 and 52
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed is the number of participants available for analysis at the specific time point. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 52 | 1.0 percentage of CD4+ T cells | Standard Deviation 5.39 |
| Placebo | Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Baseline | 78.2 percentage of CD4+ T cells | Standard Deviation 8.6 |
| Placebo | Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 26 | 1.2 percentage of CD4+ T cells | Standard Deviation 6 |
| Alogliptin 25 mg | Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Baseline | 77.7 percentage of CD4+ T cells | Standard Deviation 7.23 |
| Alogliptin 25 mg | Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 26 | 1.6 percentage of CD4+ T cells | Standard Deviation 7.2 |
| Alogliptin 25 mg | Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 52 | 0.8 percentage of CD4+ T cells | Standard Deviation 4.89 |
Secondary
Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52
Time frame: Baseline, Weeks 26 and 52
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed is the number of participants available for analysis at the specific time point. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Baseline | 59.7 percentage of CD8+ T cells | Standard Deviation 13.51 |
| Placebo | Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 26 | -0.2 percentage of CD8+ T cells | Standard Deviation 9.15 |
| Placebo | Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 52 | 1.0 percentage of CD8+ T cells | Standard Deviation 7.63 |
| Alogliptin 25 mg | Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Baseline | 59.6 percentage of CD8+ T cells | Standard Deviation 15.3 |
| Alogliptin 25 mg | Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 26 | 1.7 percentage of CD8+ T cells | Standard Deviation 8.76 |
| Alogliptin 25 mg | Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 | Change From Baseline at Week 52 | -0.3 percentage of CD8+ T cells | Standard Deviation 10.51 |
Secondary
Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52
Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Weeks 12, 18, 39 and 52 relative to Baseline. MMRM was used for the analysis.
Time frame: Baseline and Weeks 12, 18, 39 and 52
Population: FAS included all randomized participants in the safety set. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 12 | -0.319 percentage of HbA1c | Standard Deviation 0.2173 |
| Placebo | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 18 | -0.206 percentage of HbA1c | Standard Deviation 0.2458 |
| Placebo | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 39 | 0.502 percentage of HbA1c | Standard Deviation 0.2802 |
| Placebo | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 52 | 0.764 percentage of HbA1c | Standard Deviation 0.3118 |
| Alogliptin 25 mg | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 52 | 0.281 percentage of HbA1c | Standard Deviation 0.3199 |
| Alogliptin 25 mg | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 12 | -0.365 percentage of HbA1c | Standard Deviation 0.2223 |
| Alogliptin 25 mg | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 39 | 0.091 percentage of HbA1c | Standard Deviation 0.2866 |
| Alogliptin 25 mg | Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change From Baseline at Week 18 | -0.202 percentage of HbA1c | Standard Deviation 0.2529 |
Comparison: Change From Baseline at Week 12p-value: =0.86395% CI: [-0.567, 0.476]MMRM
Comparison: Change From Baseline at Week 18p-value: =0.9995% CI: [-0.614, 0.622]MMRM
Comparison: Change From Baseline at Week 39p-value: =0.26495% CI: [-1.139, 0.316]MMRM
Comparison: Change From Baseline at Week 52p-value: =0.2595% CI: [-1.314, 0.348]MMRM
Secondary
Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings
Time frame: Week 26 and 52
Population: Safety Set included all participants who took at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 26: Abnormal, Not Clinically Significant | 7 participants |
| Placebo | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 26: Abnormal, Clinically Significant | 2 participants |
| Placebo | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 52: Abnormal, Not Clinically Significant | 7 participants |
| Placebo | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 52: Abnormal, Clinically Significant | 1 participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 52: Abnormal, Clinically Significant | 0 participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 26: Abnormal, Not Clinically Significant | 6 participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 52: Abnormal, Not Clinically Significant | 6 participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | Week 26: Abnormal, Clinically Significant | 0 participants |
Secondary
Percentage of Participants With Abnormal Safety Laboratory Findings
The percentage of participants with any abnormal standard safety laboratory values (hematology, serum chemistry, and urinalysis) were collected throughout study. Abnormal values for hematology included hematocrit (percentage of hematocrit \[%\]), hemoglobin (grams per liter \[g/L\]), erythrocyte mean corpuscular volume (MCV)(femtoliter \[fL\]), erythrocytes (10\^12/L), and leukocytes (10\^9/L). Abnormal values for serum chemistry included for alanine aminotransferase (units per liter \[U/L\]), aspartate aminotransferase (U/L), cholesterol (millimoles per liter \[mmol/L\]), gamma glutamyl transferase (U/L), glucose (mmol/L): \< 2.8 mmol/L, potassium (mmol/L), sodium (mmol/L), and triglycerides (mmol/L). ULN is upper limit of normal and LLN is lower limit of normal.
Time frame: From Day 1 to end of treatment period (up to 52 weeks)
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed is the number of participants available for analysis at the specific time point. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Alanine Aminotransferase (U/L): >= 3 x ULN | 10.7 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Aspartate Aminotransferase (U/L): >= 3 x ULN | 2.7 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Cholesterol (mmol/L): >7.72 mmol/L | 1.3 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Gamma Glutamyl Transferase (U/L): >= 3 x ULN | 2.7 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Glucose (mmol/L): < 2.8 mmol/L | 13.3 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Glucose (mmol/L): >19.4 mmol/L | 10.7 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Sodium (mmol/L): <130 mmol/L | 1.3 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Triglycerides (mmol/L): >2.5x ULN | 6.7 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Hematocrit (%): >1.2 x ULN | 9.5 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Hemoglobin (g/L): >1.2 x ULN | 4.1 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Erythrocyte Mean Corpuscular Volume (fL): <70 fL | 2.7 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Erythrocytes (10^12/L): >1.2 x ULN | 1.4 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | Leukocytes (10^9/L): >1.5 x ULN | 2.7 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Erythrocytes (10^12/L): >1.2 x ULN | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Erythrocyte Mean Corpuscular Volume (fL): <70 fL | 2.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Triglycerides (mmol/L): >2.5x ULN | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Alanine Aminotransferase (U/L): >= 3 x ULN | 5.6 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Erythrocyte Mean Corpuscular Volume (fL): >100 fL | 2.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Hematocrit (%): >1.2 x ULN | 8.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Cholesterol (mmol/L): >7.72 mmol/L | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Hemoglobin (g/L): < 0.8 x LLN | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Gamma Glutamyl Transferase (U/L): >= 3 x ULN | 6.9 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Leukocytes (10^9/L): >1.5 x ULN | 2.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Glucose (mmol/L): < 2.8 mmol/L | 20.5 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Hemoglobin (g/L): >1.2 x ULN | 2.8 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Glucose (mmol/L): >19.4 mmol/L | 13.7 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Potassium (mmol/L): <3.0 mmol/L | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | Phosphate (mmol/L): >2.00 mmol/L | 1.4 percentage of participants |
Secondary
Percentage of Participants With Abnormal Vital Signs Values
Vital signs included body temperature (oral or tympanic measurement), respiratory rate, blood pressure \[systolic blood pressure (SBP) and diastolic blood pressure (DBP)\] resting more than 5 minutes, and pulse (beats per minute). Data for participants with abnormal vital signs was reported. The percentage of participants are calculated based on the participants with non-missing data at that time-point.
Time frame: From Day 1 to end of treatment period (up to 52 weeks)
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed are the number of participants with data available for analysis for given category. The percentages are rounded off to the next decimal value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Abnormal Vital Signs Values | SBP (millimeters of mercury [mmHg]): >150 | 1.3 percentage of participants |
| Placebo | Percentage of Participants With Abnormal Vital Signs Values | DBP (mmHg): >95 | 4.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Vital Signs Values | Pulse Rate (beats per minute [bpm]): <50 | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Vital Signs Values | Pulse Rate (beats per minute [bpm]): >120 | 1.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Vital Signs Values | Temperature (Celsius [C]): <35.6 | 3.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Vital Signs Values | DBP (mmHg): >95 | 4.2 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Abnormal Vital Signs Values | SBP (millimeters of mercury [mmHg]): >150 | 2.8 percentage of participants |
Secondary
Percentage of Participants With Clinically Significant Physical Examination Findings
Physical examination included examination of the following body systems: (1) respiratory system; (2) cardiovascular system; (3) nervous system (4) dermatologic system; and (5) gastrointestinal system. A summarized data for the above body systems was reported for participants with clinically significant findings.
Time frame: From Day 1 to end of treatment period (up to 52 weeks)
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed is the number of participants available for analysis at the specific time point. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 39 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 12 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 45 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 52 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 26 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 18 | 0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 32 | 0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 52 | 0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 12 | 0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 18 | 0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 26 | 0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Clinically Significant Physical Examination Findings | Week 39 | 0 percentage of participants |
Secondary
Percentage of Participants With Hypoglycemia
Mild to moderate hypoglycemia (abnormal low blood sugar) was defined as blood glucose less than (\<) 60 milligram per deciliter (mg/dL) (3.33 millimole per liter \[mmol/L\]) in the presence of symptoms, or blood glucose \<50 mg/dL (2.78 mmol/L) with or without symptoms. Severe hypoglycemia was defined as any episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, associated with a documented blood glucose \<60 mg/dL (3.33 mmol/L) (unless the clinical situation makes obtaining a blood glucose difficult \[example, it involves coma or seizure\]).
Time frame: From Day 1 to end of treatment period (up to 52 weeks)
Population: Safety Set included all participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Hypoglycemia | 7.9 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Hypoglycemia | 5.3 percentage of participants |
Secondary
Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions
The percentage of participants are calculated based on the participants with non-missing data at that time-point.
Time frame: From Day 1 to end of treatment period (up to 52 weeks)
Population: Safety Set included all participants who took at least 1 dose of study medication. Number analyzed are the number of participants with data available for analysis for given category. The percentages are rounded off to the next decimal value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Sinus Infection | 9.1 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Bladder Infection | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Upper Respiratory Infection | 18.2 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Low Urinary Tract Infection | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Upper Respiratory Tract Infection | 9.1 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | COVID-19 Infection | 9.1 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Lower Urinary Tract Infection | 9.1 percentage of participants |
| Placebo | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Lower Respiratory Tract Infection | 9.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Lower Urinary Tract Infection | 0.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Bladder Infection | 11.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | COVID-19 Infection | 0.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Low Urinary Tract Infection | 11.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Sinus Infection | 11.1 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Upper Respiratory Infection | 44.4 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Upper Respiratory Tract Infection | 0.0 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | Lower Respiratory Tract Infection | 11.1 percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Time frame: From the study start up to end of the study (up to 54 weeks)
Population: Safety Set included all participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 76.3 percentage of participants |
| Alogliptin 25 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | 80.0 percentage of participants |