Comparative Study to Evaluate Efficacy and Safety When Me... | NCT02068443

NCT02068443

ID	Type	Description	Link
JapicCTI-132377	Other Identifier	Japic CTI
U1111-1151-6515	Registry Identifier	Universal Trial Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Alogliptin Alone	Active Comparator	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.	Drug: Alogliptin Drug: Metformin hydrochloride Placebo
Alogliptin + Metformin Hydrochloride QD	Experimental	Alogliptin 25 mg, tablets, orally, once, daily, after breakfast and metformin hydrochloride 500 mg QD (250 mg x 2 tablets, once daily), tablets, orally, once, daily, after breakfast and 1 metformin hydrochloride placebo-matching, tablet, orally, once, daily, after dinner for 24 weeks.	Drug: Alogliptin Drug: Metformin hydrochloride Drug: Metformin hydrochloride Placebo
Alogliptin + Metformin Hydrochloride BID	Active Comparator	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.	Drug: Alogliptin Drug: Metformin hydrochloride Drug: Metformin hydrochloride Placebo

Name	Type	Description	Arm Group Labels	Other Names
Alogliptin	Drug	Alogliptin tablets	Alogliptin + Metformin Hydrochloride BID Alogliptin + Metformin Hydrochloride QD Alogliptin Alone

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Baseline and End of Treatment (EOT) (Up to Week 24)

Secondary Outcomes

Measure	Description	Time Frame
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.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a diagnosis of type 2 diabetes mellitus.
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).
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).
Has been on a certain diet therapy and exercise therapy (if any) during the screening period.
Has been receiving alogliptin on a stable dose and regimen (after breakfast, 25 mg/day) during the screening period.
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).
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.
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.
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.
Is treated in outpatient settings during the screening period.
In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
Signs and dates a written, informed consent form prior to the initiation of any study procedures.

Exclusion Criteria:

Has received other antidiabetic drugs than alogliptin (including insulin preparations and glucagon-like peptidase-1 [GLP-1] analog preparations) during the screening period.
Has clinical manifestations of hepatic impairment.
Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 × upper limit of normal during the screening period.
Has clinical manifestations of renal impairment, including mild impairment.
Has a history of lactic acidosis.
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.
Has dehydration or gastrointestinal dysfunction such as diarrhea or vomiting, which may cause dehydrated state.
Has malnutrition, starved state, hyposthenia, pituitary gland dysfunction or adrenal insufficiency.
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).
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.
Has a systolic blood pressure ≥ 180 mmHg or a diastolic blood pressure ≥ 110 mmHg during the screening period.
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).
Has any malignancy.
Has a history of hypersensitivity or allergies to dipeptidyl-peptidase-4 (DPP-4) inhibitors or biguanides.
Is a habitual drinker consuming more than 100 mL of alcohol on average daily.
Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol dependence.
Requires an excluded medication or a prohibited matter during the study.
Has received combination therapy of alogliptin benzoate and metformin hydrochloride in a previous clinical study or as a therapeutic agent.
Has received any investigational compound within 12 weeks prior to the start of the screening period (Week -12).
Is a participant in another clinical study at the time of signing informed consent.
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.
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.
Is considered ineligible for the study for any other reason by the investigator or subinvestigator.

Contacts/Locations Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Alogliptin + Metformin Hydrochloride QD

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All randomized participants.

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00057.2± 10.07 BG00156.9± 8.79 BG00257.6± 9.72 BG003

Age, Customized

Number

participants

Title

Denominators

Categories

< 65 years

Title	Measurements
	BG00052 BG001119 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00019 BG00142 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Japan

Title	Measurements
	BG00071 BG001152 BG002

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000165.3± 8.89 BG001164.6± 8.82 BG002

Body Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00068.00± 13.702 BG00169.48± 13.074 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00024.72± 3.764 BG00125.61± 4.231 BG002

Duration of Type 2 Diabetes

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0007.73± 4.666 BG0017.02± 5.257 BG002

Estimated Glomerular Filtration Rate (eGFR)

Mean

Standard Deviation

mL/min/1.73 m^2

Title

Denominators

Categories

Title	Measurements
	BG00088.2± 15.99 BG00191.0± 16.82 BG002

Hemoglobin A1c (HbA1c) [National Glycohemoglobin Standardization Program (NGSP)]

Mean

Standard Deviation

percent

Title

Denominators

Categories

Title	Measurements
	BG0007.77± 0.780 BG0017.82± 0.820 BG002

Fasting Blood Glucose

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000162.4± 31.03 BG001164.7± 31.02 BG002

Fasting Insulin

Mean

Standard Deviation

μU/mL

Title

Denominators

Categories

Title	Measurements
	BG0009.918± 6.8797 BG0019.464± 6.7691 BG002

Fasting Glucagon

Mean

Standard Deviation

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG00091.7± 30.03 BG00186.8± 21.27 BG002

Homeostasis Model Assessment of Insulin Resistance (HOMA-R)

Mean

Standard Deviation

unitless

Title

Denominators

Categories

Title	Measurements
	BG0004.05± 3.238 BG0013.87± 2.869 BG002

Homeostasis Model Assessment Beta Cell Index (HOMA-β)

Mean

Standard Deviation

percent

Title

Denominators

Categories

Title	Measurements
	BG00038.64± 29.181 BG00136.05± 27.848 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

percent

Baseline and End of Treatment (EOT) (Up to Week 24)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts
Participants	OG00071 OG001152 OG002151

Title

Denominators

Categories

Title	Measurements
	OG0000.16± 0.072 OG001-0.49± 0.049 OG002-0.60± 0.049

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						LS Mean Difference	-0.65	Standard Error of the Mean	0.087	2-Sided	95	-0.821	-0.480			Estimated Value was for the difference between Alogliptin + Metformin Hydrochloride QD and Alogliptin alone (Metformin QD - Alogliptin alone).		Superiority or Other (legacy)
OG001 OG002

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.

FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.

Posted

Mean

Standard Deviation

percent

Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.

Posted

Mean

Standard Deviation

percent

Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

FAS included all randomized participants who received at least 1 dose of study drug.

Posted

Number

percentage of participants

Baseline and EOT (Up to Week 24)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.

Posted

Mean

Standard Deviation

mg/dL

Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.

Posted

Mean

Standard Deviation

mg/dL

Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and EOT (Up to Week 24)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Safety Analysis Set included all participants who received at least 1 dose of study drug.

Posted

Number

percentage of participants

24 Weeks

ID	Title	Description
OG000	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.
OG001	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.

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.

Safety Analysis Set included all participants who received at least 1 dose of study drug.

Posted

Number

percentage of participants

24 Weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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]).

Safety Analysis Set included all participants who received at least 1 dose of study drug.

Posted

Number

percentage of participants

24 Weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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".

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.

Posted

Number

participants

Baseline and Weeks 12 and 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	1	71	15	71
EG001	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.	3	152	25	152
EG002	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.	0	151	27	151

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diverticulitis	Infections and infestations	MedDRA version 17.1	Systematic Assessment	EG0001 affected71 at risk EG0010 affected152 at risk EG0020 affected151 at risk
Brain contusion	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Fall	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Limb crushing injury	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Pulmonary contusion	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Scapula fracture	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Splenic injury	Injury, poisoning and procedural complications	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA version 17.1	Systematic Assessment	EG0000 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA version 17.1	Systematic Assessment	EG0008 affected71 at risk EG00122 affected152 at risk EG00219 affected151 at risk
Pharyngitis	Infections and infestations	MedDRA version 17.1	Systematic Assessment	EG0003 affected71 at risk EG0013 affected152 at risk EG0029 affected151 at risk
Hypoaesthesia	Nervous system disorders	MedDRA version 17.1	Systematic Assessment	EG0004 affected71 at risk EG0011 affected152 at risk EG0020 affected151 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2

ID	Term
C520853	alogliptin
D008687	Metformin

Facility	Status	City	State	ZIP	Country	Contacts
		Nagoya	Aichi-ken		Japan

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals