Type 2 Diabetes Mellitus
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study was to evaluate the efficacy and safety of 24-week treatment with metformin hydrochloride 500 mg once daily added on to alogliptin (SYR-322) 25 mg in type 2 diabetic patients with inadequate glycemic control despite treatment with alogliptin 25 mg in addition to diet and exercise therapy.
Detailed description
The drugs being tested in this study are called alogliptin and metformin hydrochloride. Alogliptin in combination with metformin hydrochloride was being tested to treat people who have Type 2 diabetes mellitus (T2DM) with inadequate glycemic control despite treatment with alogliptin in addition to diet and exercise. This study looked at the efficacy and safety of alogliptin 25 mg once daily (QD) + metformin hydrochloride 500 mg QD compared to alogliptin 25 mg QD + metformin hydrochloride 250 mg twice daily (BID) and alogliptin 25 mg QD administered alone. The study enrolled 374 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need): * Alogliptin 25 mg QD + metformin hydrochloride 500 mg QD * Alogliptin 25 mg QD + metformin hydrochloride 250 mg BID * Alogliptin 25 mg QD This multi-center trial was conducted in Japan. The overall time to participate in this study was 36 weeks (12-week screening period and 24-week treatment period). Participants made multiple visits to the clinic including a final visit 24 weeks after the start of study medication.
Interventions
DRUGAlogliptin
Alogliptin tablets
DRUGMetformin hydrochloride
Metformin hydrochloride tablets
DRUGMetformin hydrochloride Placebo
Metformin hydrochloride placebo-matching tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Has a diagnosis of type 2 diabetes mellitus. 2. Has a hemoglobin A1c (HbA1c) (National glycohemoglobin standardization program \[NGSP\]) of ≥6.9% to \<10.5% at 8 weeks after the start of the screening period (Week -4). 3. Has an HbA1c (NGSP) difference between 4 weeks after the start of the screening period (Week -8) and 8 weeks after the start of the screening period (Week -4) being within 10.0% (rounded off to the first decimal place) of the value at 4 weeks after the start of the screening period (Week -8). 4. Has been on a certain diet therapy and exercise therapy (if any) during the screening period. 5. Has been receiving alogliptin on a stable dose and regimen (after breakfast, 25 mg/day) during the screening period. 6. In the opinion of investigator or subinvestigator, the participant is considered appropriate to receive a biguanide as an add-on to alogliptin, at the end of the screening period (Week 0). 7. In the opinion of investigator or subinvestigator, the participant is unlikely to require changes in the dose of antihypertensive agents (including discontinuation and suspension) or an additional antihypertensive agent during the study. 8. Is a male and female aged ≥20 years to \<75 years. Participants aged ≥65 years to \<75 years need to be considered eligible for the enrollment by the investigator or subinvestigator at the end of the screening period (Week 0) taking into consideration the cardiovascular disorders pulmonary function disorders, renal function, hepatic function, etc. 9. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of informed consent throughout the duration of the study. 10. Is treated in outpatient settings during the screening period. 11. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements. 12. Signs and dates a written, informed consent form prior to the initiation of any study procedures.
Exclusion criteria
1. Has received other antidiabetic drugs than alogliptin (including insulin preparations and glucagon-like peptidase-1 \[GLP-1\] analog preparations) during the screening period. 2. Has clinical manifestations of hepatic impairment. 3. Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 × upper limit of normal during the screening period. 4. Has clinical manifestations of renal impairment, including mild impairment. 5. Has a history of lactic acidosis. 6. Has any cardiovascular disease including shock, heart failure, myocardial infarction and pulmonary embolism, any serious pulmonary function disorder, or any other condition predisposing him/her to hypoxemia. 7. Has dehydration or gastrointestinal dysfunction such as diarrhea or vomiting, which may cause dehydrated state. 8. Has malnutrition, starved state, hyposthenia, pituitary gland dysfunction or adrenal insufficiency. 9. Has any serious cardiac disease, any serious cerebrovascular disorder, or any serious pancreatic or hematological disease (eg, the participant requiring inpatient treatment or having been hospitalized for treatment within 24 weeks prior to the start of the screening period). 10. In the opinion of the investigator or subinvestigator, the participant has clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes during the screening period. 11. Has a systolic blood pressure ≥ 180 mmHg or a diastolic blood pressure ≥ 110 mmHg during the screening period. 12. Has a condition requiring insulin for blood glucose control (eg, severe ketosis, diabetic coma or precoma, type 1 diabetes, severe infection, pre- or post-operative condition, or serious trauma). 13. Has any malignancy. 14. Has a history of hypersensitivity or allergies to dipeptidyl-peptidase-4 (DPP-4) inhibitors or biguanides. 15. Is a habitual drinker consuming more than 100 mL of alcohol on average daily. 16. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol dependence. 17. Requires an excluded medication or a prohibited matter during the study. 18. Has received combination therapy of alogliptin benzoate and metformin hydrochloride in a previous clinical study or as a therapeutic agent. 19. Has received any investigational compound within 12 weeks prior to the start of the screening period (Week -12). 20. Is a participant in another clinical study at the time of signing informed consent. 21. If female, the participant is pregnant or lactating; intending to become pregnant between the time of signing informed consent and the end of the study; or intending to donate ova during such period. 22. Is a study site employee, is its immediate family member, is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress. 23. Is considered ineligible for the study for any other reason by the investigator or subinvestigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period | Baseline and End of Treatment (EOT) (Up to Week 24) | The change in the value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at End of Treatment Period relative to Baseline. A negative change from Baseline indicates improvement. An Analysis of Covariate (ANCOVA) model with change from Baseline as a dependent variable and Baseline and treatment as independent variables was used for main analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c (NGSP) | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24) | The value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and EOT. |
| Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | Baseline and EOT (Up to Week 24) | HbA1c (NGSP) is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound. The percentage of participants with HbA1c levels of ≥6.0, ≥7.0 and ≥8.0 at the end of Screening (Baseline) with change to target values \<6.0, \<7.0 and \<8.0 respectively at EOT. |
| Change From Baseline in Fasting Blood Glucose | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24) | The change in the value of the fasting plasma glucose collected at Weeks 2, 4, 8, 12, 16, 20 and 24 relative to Baseline. A negative change from Baseline indicates improvement. |
| Fasting Blood Glucose | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24) | The value of the fasting plasma glucose collected at Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT. |
| Change From Baseline in HbA1c (NGSP) | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24) | The change in the value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Weeks 2, 4, 8, 12, 16, 20, 24, and EOT relative to Baseline. A negative change from Baseline indicates improvement. |
| Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | 24 Weeks | The percentage of participants with any clinically relevant safety laboratory changes (chemistry, hematology and urinalysis) collected throughout study and recorded as AEs. |
| Percentage of Participants With TEAEs Related to Vital Signs | 24 Weeks | Vital signs included sitting systolic and diastolic blood pressures (mmHg) (measured after resting for ≥ 5 minutes) and pulse rate (beats per minute \[bpm\]). |
| Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Baseline and Weeks 12 and 24 | Number of participants who had ECG findings changed from normal or abnormal but not clinically relevant at Baseline to abnormal and clinically relevant. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | 24 Weeks | An Adverse Event (AE) is 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. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 34 investigative sites in Japan from 06 February 2014 (first patient to sign the informed consent form) to 28 February 2015.
Pre-assignment details
Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled equally in a 2:2:1 ratio to 1 of 3 treatment groups: alogliptin in combination with 500 mg total dose metformin hydrochloride administered either once a day (QD) or twice a day (BID) and alogliptin alone.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin Alone Alogliptin 25 mg, tablets, orally, once, daily, after breakfast and metformin hydrochloride placebo-matching, tablets, orally, 2 tablets after breakfast and 1 tablet after dinner for 24 weeks. | 71 |
| Alogliptin + Metformin Hydrochloride QD Alogliptin 25 mg, tablets, orally, once, daily, after breakfast and metformin hydrochloride 500 mg QD (250 mg x 2 tablets, once daily), tablets, orally, QD (once daily), after breakfast and 1 metformin hydrochloride placebo-matching, tablet, orally, once, daily, after dinner for 24 weeks. | 152 |
| Alogliptin + Metformin Hydrochloride BID Alogliptin 25 mg, tablets, orally, once, daily, after breakfast and metformin hydrochloride 250 mg BID (twice daily), tablets, orally, 1 tablet after breakfast and 1 tablet after dinner and 1 metformin hydrochloride placebo-matching, tablet, orally, once, daily, after breakfast for 24 weeks. | 151 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Other Reason Not Specified | 1 | 0 | 0 |
| Overall Study | Pretreatment Event/Adverse Event | 0 | 5 | 2 |
| Overall Study | Voluntary Withdrawal | 4 | 0 | 1 |
Baseline characteristics
| Characteristic | Alogliptin Alone | Alogliptin + Metformin Hydrochloride QD | Alogliptin + Metformin Hydrochloride BID | Total |
|---|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 10.07 | 56.9 years STANDARD_DEVIATION 8.79 | 57.6 years STANDARD_DEVIATION 9.72 | 57.2 years STANDARD_DEVIATION 9.4 |
| Age, Customized < 65 years | 52 participants | 119 participants | 109 participants | 280 participants |
| Age, Customized ≥ 65 years | 19 participants | 33 participants | 42 participants | 94 participants |
| Body Mass Index (BMI) | 24.72 kg/m^2 STANDARD_DEVIATION 3.764 | 25.61 kg/m^2 STANDARD_DEVIATION 4.231 | 25.52 kg/m^2 STANDARD_DEVIATION 4.344 | 25.41 kg/m^2 STANDARD_DEVIATION 4.196 |
| Body Weight | 68.00 kg STANDARD_DEVIATION 13.702 | 69.48 kg STANDARD_DEVIATION 13.074 | 69.55 kg STANDARD_DEVIATION 14.927 | 69.23 kg STANDARD_DEVIATION 13.943 |
| Duration of Type 2 Diabetes | 7.73 years STANDARD_DEVIATION 4.666 | 7.02 years STANDARD_DEVIATION 5.257 | 7.04 years STANDARD_DEVIATION 5.38 | 7.16 years STANDARD_DEVIATION 5.195 |
| Estimated Glomerular Filtration Rate (eGFR) | 88.2 mL/min/1.73 m^2 STANDARD_DEVIATION 15.99 | 91.0 mL/min/1.73 m^2 STANDARD_DEVIATION 16.82 | 87.9 mL/min/1.73 m^2 STANDARD_DEVIATION 17.86 | 89.2 mL/min/1.73 m^2 STANDARD_DEVIATION 17.11 |
| Fasting Blood Glucose | 162.4 mg/dL STANDARD_DEVIATION 31.03 | 164.7 mg/dL STANDARD_DEVIATION 31.02 | 165.9 mg/dL STANDARD_DEVIATION 30.92 | 164.7 mg/dL STANDARD_DEVIATION 30.92 |
| Fasting Glucagon | 91.7 pg/mL STANDARD_DEVIATION 30.03 | 86.8 pg/mL STANDARD_DEVIATION 21.27 | 89.3 pg/mL STANDARD_DEVIATION 27.98 | 88.8 pg/mL STANDARD_DEVIATION 25.89 |
| Fasting Insulin | 9.918 μU/mL STANDARD_DEVIATION 6.8797 | 9.464 μU/mL STANDARD_DEVIATION 6.7691 | 9.342 μU/mL STANDARD_DEVIATION 6.0645 | 9.501 μU/mL STANDARD_DEVIATION 6.499 |
| Height | 165.3 cm STANDARD_DEVIATION 8.89 | 164.6 cm STANDARD_DEVIATION 8.82 | 164.6 cm STANDARD_DEVIATION 9.12 | 164.8 cm STANDARD_DEVIATION 8.94 |
| Hemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)] | 7.77 percent STANDARD_DEVIATION 0.78 | 7.82 percent STANDARD_DEVIATION 0.82 | 7.89 percent STANDARD_DEVIATION 0.791 | 7.84 percent STANDARD_DEVIATION 0.8 |
| Homeostasis Model Assessment Beta Cell Index (HOMA-β) | 38.64 percent STANDARD_DEVIATION 29.181 | 36.05 percent STANDARD_DEVIATION 27.848 | 34.27 percent STANDARD_DEVIATION 23.638 | 35.82 percent STANDARD_DEVIATION 26.464 |
| Homeostasis Model Assessment of Insulin Resistance (HOMA-R) | 4.05 unitless STANDARD_DEVIATION 3.238 | 3.87 unitless STANDARD_DEVIATION 2.869 | 3.92 unitless STANDARD_DEVIATION 2.82 | 3.93 unitless STANDARD_DEVIATION 2.916 |
| Region of Enrollment Japan | 71 participants | 152 participants | 151 participants | 374 participants |
| Sex: Female, Male Female | 19 Participants | 42 Participants | 45 Participants | 106 Participants |
| Sex: Female, Male Male | 52 Participants | 110 Participants | 106 Participants | 268 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 | 15 / 71 | 25 / 152 | 27 / 151 |
| serious Total, serious adverse events | 1 / 71 | 3 / 152 | 0 / 151 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period
The change in the value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at End of Treatment Period relative to Baseline. A negative change from Baseline indicates improvement. An Analysis of Covariate (ANCOVA) model with change from Baseline as a dependent variable and Baseline and treatment as independent variables was used for main analyses.
Time frame: Baseline and End of Treatment (EOT) (Up to Week 24)
Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alogliptin Alone | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period | 0.16 percent | Standard Error 0.072 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period | -0.49 percent | Standard Error 0.049 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period | -0.60 percent | Standard Error 0.049 |
95% CI: [-0.821, -0.48]
95% CI: [-0.026, 0.247]
Secondary
Change From Baseline in Fasting Blood Glucose
The change in the value of the fasting plasma glucose collected at Weeks 2, 4, 8, 12, 16, 20 and 24 relative to Baseline. A negative change from Baseline indicates improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Population: FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 24 (n=64, 146, 148) | 8.0 mg/dL | Standard Deviation 21.85 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 20 (n=65, 146, 148) | 6.6 mg/dL | Standard Deviation 23.87 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 2 (n=71, 152, 151) | 0.4 mg/dL | Standard Deviation 16.62 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | EOT (n=71, 152, 151) | 7.4 mg/dL | Standard Deviation 26.89 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 16 (n=66, 148, 148) | 0.4 mg/dL | Standard Deviation 22.63 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 12 (n=67, 148, 148) | 1.5 mg/dL | Standard Deviation 20.42 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 4 (n=70, 150, 150) | -0.9 mg/dL | Standard Deviation 26.32 |
| Alogliptin Alone | Change From Baseline in Fasting Blood Glucose | Week 8 (n=68, 149, 149) | -2.1 mg/dL | Standard Deviation 23.3 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 16 (n=66, 148, 148) | -13.0 mg/dL | Standard Deviation 24.7 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 4 (n=70, 150, 150) | -16.4 mg/dL | Standard Deviation 20.79 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 20 (n=65, 146, 148) | -11.3 mg/dL | Standard Deviation 23.34 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 24 (n=64, 146, 148) | -7.2 mg/dL | Standard Deviation 26.53 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | EOT (n=71, 152, 151) | -7.6 mg/dL | Standard Deviation 26.41 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 2 (n=71, 152, 151) | -16.6 mg/dL | Standard Deviation 18.99 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 8 (n=68, 149, 149) | -18.4 mg/dL | Standard Deviation 20.9 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in Fasting Blood Glucose | Week 12 (n=67, 148, 148) | -15.2 mg/dL | Standard Deviation 23.83 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 20 (n=65, 146, 148) | -17.6 mg/dL | Standard Deviation 25.25 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 4 (n=70, 150, 150) | -25.2 mg/dL | Standard Deviation 20.73 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 8 (n=68, 149, 149) | -23.4 mg/dL | Standard Deviation 24.13 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 16 (n=66, 148, 148) | -22.6 mg/dL | Standard Deviation 25.5 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 2 (n=71, 152, 151) | -23.7 mg/dL | Standard Deviation 20.5 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | EOT (n=71, 152, 151) | -18.2 mg/dL | Standard Deviation 25.41 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 24 (n=64, 146, 148) | -18.2 mg/dL | Standard Deviation 25.28 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in Fasting Blood Glucose | Week 12 (n=67, 148, 148) | -22.9 mg/dL | Standard Deviation 24.36 |
Secondary
Change From Baseline in HbA1c (NGSP)
The change in the value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Weeks 2, 4, 8, 12, 16, 20, 24, and EOT relative to Baseline. A negative change from Baseline indicates improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Population: FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | EOT (n=71, 152, 151) | 0.17 percent | Standard Deviation 0.616 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 20 (n=65, 146, 148) | 0.11 percent | Standard Deviation 0.568 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 4 (n=70, 150, 150) | 0.01 percent | Standard Deviation 0.316 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 2 (n=71, 152, 151) | 0.01 percent | Standard Deviation 0.197 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 12 (n=67, 148, 148) | -0.02 percent | Standard Deviation 0.518 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 24 (n=64, 146, 148) | 0.17 percent | Standard Deviation 0.628 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 16 (n=66, 148, 147) | 0.01 percent | Standard Deviation 0.543 |
| Alogliptin Alone | Change From Baseline in HbA1c (NGSP) | Week 8 (n=68, 149, 149) | -0.01 percent | Standard Deviation 0.402 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 20 (n=65, 146, 148) | -0.58 percent | Standard Deviation 0.585 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 16 (n=66, 148, 147) | -0.64 percent | Standard Deviation 0.553 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 24 (n=64, 146, 148) | -0.49 percent | Standard Deviation 0.629 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | EOT (n=71, 152, 151) | -0.49 percent | Standard Deviation 0.62 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 2 (n=71, 152, 151) | -0.14 percent | Standard Deviation 0.203 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 4 (n=70, 150, 150) | -0.28 percent | Standard Deviation 0.279 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 8 (n=68, 149, 149) | -0.50 percent | Standard Deviation 0.408 |
| Alogliptin + Metformin Hydrochloride QD | Change From Baseline in HbA1c (NGSP) | Week 12 (n=67, 148, 148) | -0.61 percent | Standard Deviation 0.53 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 4 (n=70, 150, 150) | -0.35 percent | Standard Deviation 0.298 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 24 (n=64, 146, 148) | -0.62 percent | Standard Deviation 0.659 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 12 (n=67, 148, 148) | -0.75 percent | Standard Deviation 0.565 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 8 (n=68, 149, 149) | -0.60 percent | Standard Deviation 0.454 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 20 (n=65, 146, 148) | -0.71 percent | Standard Deviation 0.626 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 2 (n=71, 152, 151) | -0.19 percent | Standard Deviation 0.212 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | EOT (n=71, 152, 151) | -0.62 percent | Standard Deviation 0.654 |
| Alogliptin + Metformin Hydrochloride BID | Change From Baseline in HbA1c (NGSP) | Week 16 (n=66, 148, 147) | -0.81 percent | Standard Deviation 0.602 |
Secondary
Fasting Blood Glucose
The value of the fasting plasma glucose collected at Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Population: FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin Alone | Fasting Blood Glucose | Week 16 (n=66, 148, 148) | 158.5 mg/dL | Standard Deviation 29.71 |
| Alogliptin Alone | Fasting Blood Glucose | Week 20 (n=65, 146, 148) | 164.6 mg/dL | Standard Deviation 31.64 |
| Alogliptin Alone | Fasting Blood Glucose | EOT (n=71, 152, 151) | 169.8 mg/dL | Standard Deviation 36.03 |
| Alogliptin Alone | Fasting Blood Glucose | Week 24 (n=64, 146, 148) | 165.9 mg/dL | Standard Deviation 31.19 |
| Alogliptin Alone | Fasting Blood Glucose | Baseline (n=71, 152, 151) | 162.4 mg/dL | Standard Deviation 31.03 |
| Alogliptin Alone | Fasting Blood Glucose | Week 8 (n=68, 149, 149) | 158.9 mg/dL | Standard Deviation 33.15 |
| Alogliptin Alone | Fasting Blood Glucose | Week 12 (n=67, 148, 148) | 161.1 mg/dL | Standard Deviation 33.43 |
| Alogliptin Alone | Fasting Blood Glucose | Week 2 (n=71, 152, 151) | 162.8 mg/dL | Standard Deviation 33.42 |
| Alogliptin Alone | Fasting Blood Glucose | Week 4 (n=70, 150, 150) | 161.4 mg/dL | Standard Deviation 37.17 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 24 (n=64, 146, 148) | 157.4 mg/dL | Standard Deviation 33.21 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Baseline (n=71, 152, 151) | 164.7 mg/dL | Standard Deviation 31.02 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 2 (n=71, 152, 151) | 148.1 mg/dL | Standard Deviation 26.7 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 12 (n=67, 148, 148) | 149.2 mg/dL | Standard Deviation 30.7 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 16 (n=66, 148, 148) | 151.4 mg/dL | Standard Deviation 32.52 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | EOT (n=71, 152, 151) | 157.1 mg/dL | Standard Deviation 32.82 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 4 (n=70, 150, 150) | 148.7 mg/dL | Standard Deviation 27.56 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 8 (n=68, 149, 149) | 146.5 mg/dL | Standard Deviation 25.21 |
| Alogliptin + Metformin Hydrochloride QD | Fasting Blood Glucose | Week 20 (n=65, 146, 148) | 153.2 mg/dL | Standard Deviation 30.92 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | EOT (n=71, 152, 151) | 147.7 mg/dL | Standard Deviation 27.2 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 4 (n=70, 150, 150) | 140.7 mg/dL | Standard Deviation 23.74 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 2 (n=71, 152, 151) | 142.3 mg/dL | Standard Deviation 25.24 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 20 (n=65, 146, 148) | 147.8 mg/dL | Standard Deviation 28.21 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 8 (n=68, 149, 149) | 142.0 mg/dL | Standard Deviation 25.35 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 24 (n=64, 146, 148) | 147.3 mg/dL | Standard Deviation 26.85 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 16 (n=66, 148, 148) | 142.9 mg/dL | Standard Deviation 26.16 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Baseline (n=71, 152, 151) | 165.9 mg/dL | Standard Deviation 30.92 |
| Alogliptin + Metformin Hydrochloride BID | Fasting Blood Glucose | Week 12 (n=67, 148, 148) | 142.5 mg/dL | Standard Deviation 27.85 |
Secondary
HbA1c (NGSP)
The value of HbA1c (NGSP) (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and EOT.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)
Population: FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin Alone | HbA1c (NGSP) | Week 2 (n=71, 152, 151) | 7.78 percent | Standard Deviation 0.824 |
| Alogliptin Alone | HbA1c (NGSP) | Week 8 (n=68, 149, 149) | 7.72 percent | Standard Deviation 0.889 |
| Alogliptin Alone | HbA1c (NGSP) | Week 12 (n=67, 148, 148) | 7.70 percent | Standard Deviation 0.987 |
| Alogliptin Alone | HbA1c (NGSP) | Week 24 (n=64, 146, 148) | 7.86 percent | Standard Deviation 0.983 |
| Alogliptin Alone | HbA1c (NGSP) | EOT (n=71, 152, 151) | 7.95 percent | Standard Deviation 1.018 |
| Alogliptin Alone | HbA1c (NGSP) | Baseline (n=71, 152, 151) | 7.77 percent | Standard Deviation 0.78 |
| Alogliptin Alone | HbA1c (NGSP) | Week 4 (n=70, 150, 150) | 7.78 percent | Standard Deviation 0.913 |
| Alogliptin Alone | HbA1c (NGSP) | Week 16 (n=66, 148, 147) | 7.70 percent | Standard Deviation 0.99 |
| Alogliptin Alone | HbA1c (NGSP) | Week 20 (n=65, 146, 148) | 7.81 percent | Standard Deviation 1.023 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | EOT (n=71, 152, 151) | 7.33 percent | Standard Deviation 0.819 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Baseline (n=71, 152, 151) | 7.82 percent | Standard Deviation 0.82 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 20 (n=65, 146, 148) | 7.23 percent | Standard Deviation 0.749 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 4 (n=70, 150, 150) | 7.55 percent | Standard Deviation 0.773 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 8 (n=68, 149, 149) | 7.32 percent | Standard Deviation 0.725 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 12 (n=67, 148, 148) | 7.19 percent | Standard Deviation 0.721 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 2 (n=71, 152, 151) | 7.67 percent | Standard Deviation 0.796 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 16 (n=66, 148, 147) | 7.16 percent | Standard Deviation 0.725 |
| Alogliptin + Metformin Hydrochloride QD | HbA1c (NGSP) | Week 24 (n=64, 146, 148) | 7.32 percent | Standard Deviation 0.798 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 24 (n=64, 146, 148) | 7.27 percent | Standard Deviation 0.805 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | EOT (n=71, 152, 151) | 7.28 percent | Standard Deviation 0.804 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 16 (n=66, 148, 147) | 7.08 percent | Standard Deviation 0.717 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Baseline (n=71, 152, 151) | 7.89 percent | Standard Deviation 0.791 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 2 (n=71, 152, 151) | 7.70 percent | Standard Deviation 0.787 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 12 (n=67, 148, 148) | 7.13 percent | Standard Deviation 0.706 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 4 (n=70, 150, 150) | 7.54 percent | Standard Deviation 0.735 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 20 (n=65, 146, 148) | 7.18 percent | Standard Deviation 0.78 |
| Alogliptin + Metformin Hydrochloride BID | HbA1c (NGSP) | Week 8 (n=68, 149, 149) | 7.28 percent | Standard Deviation 0.707 |
Secondary
Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings
Number of participants who had ECG findings changed from normal or abnormal but not clinically relevant at Baseline to abnormal and clinically relevant.
Time frame: Baseline and Weeks 12 and 24
Population: Safety Analysis Set, all participants who received at least 1 dose of study drug, with ECG values normal or abnormal not clinically significant at Baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin Alone | Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Week 12 | 0 participants |
| Alogliptin Alone | Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Week 24 | 0 participants |
| Alogliptin + Metformin Hydrochloride QD | Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Week 12 | 0 participants |
| Alogliptin + Metformin Hydrochloride QD | Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Week 24 | 0 participants |
| Alogliptin + Metformin Hydrochloride BID | Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Week 12 | 0 participants |
| Alogliptin + Metformin Hydrochloride BID | Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings | Week 24 | 2 participants |
Secondary
Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period
HbA1c (NGSP) is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound. The percentage of participants with HbA1c levels of ≥6.0, ≥7.0 and ≥8.0 at the end of Screening (Baseline) with change to target values \<6.0, \<7.0 and \<8.0 respectively at EOT.
Time frame: Baseline and EOT (Up to Week 24)
Population: FAS included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin Alone | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥7.0 at Baseline to <7.0 at EOT ( n=63, 137, 140) | 4.8 percentage of participants |
| Alogliptin Alone | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥8.0 at Baseline to <8.0 at EOT (n=26, 59, 64) | 23.1 percentage of participants |
| Alogliptin Alone | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥6.0 at Baseline to <6.0 at EOT (n=71, 152, 151) | 0.0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥8.0 at Baseline to <8.0 at EOT (n=26, 59, 64) | 47.5 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥6.0 at Baseline to <6.0 at EOT (n=71, 152, 151) | 0.7 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥7.0 at Baseline to <7.0 at EOT ( n=63, 137, 140) | 35.0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥8.0 at Baseline to <8.0 at EOT (n=26, 59, 64) | 60.9 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥7.0 at Baseline to <7.0 at EOT ( n=63, 137, 140) | 34.3 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period | ≥6.0 at Baseline to <6.0 at EOT (n=71, 152, 151) | 1.3 percentage of participants |
Secondary
Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
The percentage of participants with any clinically relevant safety laboratory changes (chemistry, hematology and urinalysis) collected throughout study and recorded as AEs.
Time frame: 24 Weeks
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin Alone | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Creatine Phosphokinase increased | 0 percentage of participants |
| Alogliptin Alone | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Lipase increased | 0 percentage of participants |
| Alogliptin Alone | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Lactic Acid increased | 0 percentage of participants |
| Alogliptin Alone | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Gamma-glutamyltransferase increased | 0 percentage of participants |
| Alogliptin Alone | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Albumin decreased | 0 percentage of participants |
| Alogliptin Alone | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Amylase increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Gamma-glutamyltransferase increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Lipase increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Creatine Phosphokinase increased | 2.0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Lactic Acid increased | 1.3 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Amylase increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Albumin decreased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Lipase increased | 2.0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Amylase increased | 2.0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Creatine Phosphokinase increased | 0.7 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Albumin decreased | 0.7 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Blood Lactic Acid increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Gamma-glutamyltransferase increased | 0.7 percentage of participants |
Secondary
Percentage of Participants With TEAEs Related to Vital Signs
Vital signs included sitting systolic and diastolic blood pressures (mmHg) (measured after resting for ≥ 5 minutes) and pulse rate (beats per minute \[bpm\]).
Time frame: 24 Weeks
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin Alone | Percentage of Participants With TEAEs Related to Vital Signs | Hypertension | 1.4 percentage of participants |
| Alogliptin Alone | Percentage of Participants With TEAEs Related to Vital Signs | Blood Pressure increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Related to Vital Signs | Hypertension | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With TEAEs Related to Vital Signs | Blood Pressure increased | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Related to Vital Signs | Hypertension | 0 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With TEAEs Related to Vital Signs | Blood Pressure increased | 0.7 percentage of participants |
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)
An Adverse Event (AE) is 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. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: 24 Weeks
Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin Alone | Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | 57.7 percentage of participants |
| Alogliptin + Metformin Hydrochloride QD | Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | 50.7 percentage of participants |
| Alogliptin + Metformin Hydrochloride BID | Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | 52.3 percentage of participants |