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CompletedNCT02068443Updated Sep 28, 2023Results posted

Comparative Study to Evaluate Efficacy and Safety When Metformin Hydrochloride 500 mg Once Daily is Added on to SYR-322 25 mg in Type 2 Diabetic Patients With Inadequate Glycemic Control Despite Treatment With SYR-322 25 mg in Addition to Diet and Exercise Therapy

A Phase 3 interventional study of Alogliptin and Metformin hydrochloride in Type 2 Diabetes Mellitus, sponsored by Takeda. Completed at 27 sites in Japan. Open to participants aged 20 Years to 74 Years. Per ClinicalTrials.gov, last updated 2023-09-28.

Sponsored by Takeda · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
374
Allocation
Randomized
Ages
20 Years to 74 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Type 2 Diabetes Mellitus

Keywords

  • Drug therapy
03

In context

Diabetes Mellitus, Type 2

9,359 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,318 are open to participants now.

This study's enrollment of 374 is above the median of 80 across 7,525 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 74 Years
Sexes eligible
All
Accepts 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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
374 participants (actual)

Study arms

  • Active comparator
    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.

    Drug: Alogliptin · Drug: Metformin hydrochloride Placebo

  • Experimental
    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, 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

  • Active comparator
    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.

    Drug: Alogliptin · Drug: Metformin hydrochloride · Drug: Metformin hydrochloride Placebo

Interventions

  • DrugAlogliptin

    Alogliptin tablets

    Also known as: SYR-322, Nesina®

  • DrugMetformin hydrochloride

    Metformin hydrochloride tablets

    Also known as: Glycoran®

  • DrugMetformin hydrochloride Placebo

    Metformin hydrochloride placebo-matching tablets

06

What researchers measure

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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

  7. 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

  8. 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

  9. 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

07

Results

Posted Jun 6, 2016

Participant flow

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.

Participant flow — Overall Study
MilestoneAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Started71152151
Completed64146148
Not completed763
Withdrew: Pretreatment event/adverse event052
Withdrew: Voluntary withdrawal401
Withdrew: Lack of efficacy210
Withdrew: Other reason not specified100

Outcome measures

PrimaryChange 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)
Reported as:
Least squares mean · percent
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period
percentAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period0.16 ± 0.072-0.49 ± 0.049-0.60 ± 0.049
Statistical analysis
  • Alogliptin Alone vs Alogliptin + Metformin Hydrochloride QD · Ls mean difference: -0.65 · 95% CI -0.821 to -0.480Estimated Value was for the difference between Alogliptin + Metformin Hydrochloride QD and Alogliptin alone (Metformin QD - Alogliptin alone).
  • Alogliptin + Metformin Hydrochloride QD vs Alogliptin + Metformin Hydrochloride BID · Ls mean difference: 0.11 · 95% CI -0.026 to 0.247Estimated Value was for the difference between Alogliptin + Metformin Hydrochloride QD and Alogliptin + Metformin Hydrochloride BID (Metformin QD - Metformin BID).
SecondaryChange 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)
Reported as:
Mean · percent
Change From Baseline in HbA1c (NGSP)
percentAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Week 2 (n=71, 152, 151)0.01 ± 0.197-0.14 ± 0.203-0.19 ± 0.212
Week 4 (n=70, 150, 150)0.01 ± 0.316-0.28 ± 0.279-0.35 ± 0.298
Week 8 (n=68, 149, 149)-0.01 ± 0.402-0.50 ± 0.408-0.60 ± 0.454
Week 12 (n=67, 148, 148)-0.02 ± 0.518-0.61 ± 0.530-0.75 ± 0.565
Week 16 (n=66, 148, 147)0.01 ± 0.543-0.64 ± 0.553-0.81 ± 0.602
Week 20 (n=65, 146, 148)0.11 ± 0.568-0.58 ± 0.585-0.71 ± 0.626
Week 24 (n=64, 146, 148)0.17 ± 0.628-0.49 ± 0.629-0.62 ± 0.659
EOT (n=71, 152, 151)0.17 ± 0.616-0.49 ± 0.620-0.62 ± 0.654
SecondaryHbA1c (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)
Reported as:
Mean · percent
HbA1c (NGSP)
percentAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Baseline (n=71, 152, 151)7.77 ± 0.7807.82 ± 0.8207.89 ± 0.791
Week 2 (n=71, 152, 151)7.78 ± 0.8247.67 ± 0.7967.70 ± 0.787
Week 4 (n=70, 150, 150)7.78 ± 0.9137.55 ± 0.7737.54 ± 0.735
Week 8 (n=68, 149, 149)7.72 ± 0.8897.32 ± 0.7257.28 ± 0.707
Week 12 (n=67, 148, 148)7.70 ± 0.9877.19 ± 0.7217.13 ± 0.706
Week 16 (n=66, 148, 147)7.70 ± 0.9907.16 ± 0.7257.08 ± 0.717
Week 20 (n=65, 146, 148)7.81 ± 1.0237.23 ± 0.7497.18 ± 0.780
Week 24 (n=64, 146, 148)7.86 ± 0.9837.32 ± 0.7987.27 ± 0.805
EOT (n=71, 152, 151)7.95 ± 1.0187.33 ± 0.8197.28 ± 0.804
SecondaryPercentage 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)
Reported as:
Number · percentage of participants
Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period
percentage of participantsAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
≥6.0 at Baseline to <6.0 at EOT (n=71, 152, 151)0.0 (0.197 to —)0.7 (0.203 to —)1.3 (0.212 to —)
≥7.0 at Baseline to <7.0 at EOT ( n=63, 137, 140)4.8 (0.316 to —)35.0 (0.279 to —)34.3 (0.298 to —)
≥8.0 at Baseline to <8.0 at EOT (n=26, 59, 64)23.1 (0.402 to —)47.5 (0.408 to —)60.9 (0.454 to —)
SecondaryChange 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)
Reported as:
Mean · mg/dL
Change From Baseline in Fasting Blood Glucose
mg/dLAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Week 2 (n=71, 152, 151)0.4 ± 16.62-16.6 ± 18.99-23.7 ± 20.50
Week 4 (n=70, 150, 150)-0.9 ± 26.32-16.4 ± 20.79-25.2 ± 20.73
Week 8 (n=68, 149, 149)-2.1 ± 23.30-18.4 ± 20.90-23.4 ± 24.13
Week 12 (n=67, 148, 148)1.5 ± 20.42-15.2 ± 23.83-22.9 ± 24.36
Week 16 (n=66, 148, 148)0.4 ± 22.63-13.0 ± 24.70-22.6 ± 25.50
Week 20 (n=65, 146, 148)6.6 ± 23.87-11.3 ± 23.34-17.6 ± 25.25
Week 24 (n=64, 146, 148)8.0 ± 21.85-7.2 ± 26.53-18.2 ± 25.28
EOT (n=71, 152, 151)7.4 ± 26.89-7.6 ± 26.41-18.2 ± 25.41
SecondaryFasting 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)
Reported as:
Mean · mg/dL
Fasting Blood Glucose
mg/dLAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Baseline (n=71, 152, 151)162.4 ± 31.03164.7 ± 31.02165.9 ± 30.92
Week 2 (n=71, 152, 151)162.8 ± 33.42148.1 ± 26.70142.3 ± 25.24
Week 4 (n=70, 150, 150)161.4 ± 37.17148.7 ± 27.56140.7 ± 23.74
Week 8 (n=68, 149, 149)158.9 ± 33.15146.5 ± 25.21142.0 ± 25.35
Week 12 (n=67, 148, 148)161.1 ± 33.43149.2 ± 30.70142.5 ± 27.85
Week 16 (n=66, 148, 148)158.5 ± 29.71151.4 ± 32.52142.9 ± 26.16
Week 20 (n=65, 146, 148)164.6 ± 31.64153.2 ± 30.92147.8 ± 28.21
Week 24 (n=64, 146, 148)165.9 ± 31.19157.4 ± 33.21147.3 ± 26.85
EOT (n=71, 152, 151)169.8 ± 36.03157.1 ± 32.82147.7 ± 27.20
SecondaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)
percentage of participantsAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)57.750.752.3
SecondaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
percentage of participantsAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Blood Creatine Phosphokinase increased02.00.7
Blood Lactic Acid increased01.30
Amylase increased002.0
Lipase increased002.0
Blood Albumin decreased000.7
Gamma-glutamyltransferase increased000.7
SecondaryPercentage 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
Reported as:
Number · percentage of participants
Percentage of Participants With TEAEs Related to Vital Signs
percentage of participantsAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Hypertension1.400
Blood Pressure increased000.7
SecondaryNumber 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
Reported as:
Number · participants
Number of Participants Who Had Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Findings
participantsAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
Week 12000
Week 24002

Adverse events

Collected over 24 Weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Alogliptin Alone—1/71 (1.4%)15/71 (21.1%)
Alogliptin + Metformin Hydrochloride QD—3/152 (2%)25/152 (16.4%)
Alogliptin + Metformin Hydrochloride BID—0/151 (0%)27/151 (17.9%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
DiverticulitisInfections and infestations1/710/1520/151
Brain contusionInjury, poisoning and procedural complications0/711/1520/151
ContusionInjury, poisoning and procedural complications0/711/1520/151
FallInjury, poisoning and procedural complications0/711/1520/151
Fibula fractureInjury, poisoning and procedural complications0/711/1520/151
Limb crushing injuryInjury, poisoning and procedural complications0/711/1520/151
Pulmonary contusionInjury, poisoning and procedural complications0/711/1520/151
Rib fractureInjury, poisoning and procedural complications0/711/1520/151
Road traffic accidentInjury, poisoning and procedural complications0/711/1520/151
Scapula fractureInjury, poisoning and procedural complications0/711/1520/151
Most frequent other events
Most frequent other events
EventAlogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BID
NasopharyngitisInfections and infestations8/7122/15219/151
PharyngitisInfections and infestations3/713/1529/151
HypoaesthesiaNervous system disorders4/711/1520/151

Baseline characteristics

All randomized participants.

Age, Continuous
Age, Continuous(years)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Mean57.2 ± 10.0756.9 ± 8.7957.6 ± 9.7257.2 ± 9.40
Age, Customized
Age, Customized(participants)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
< 65 years52119109280
≥ 65 years19334294
Sex: Female, Male
Sex: Female, Male(Participants)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Female194245106
Male52110106268
Region of Enrollment
Region of Enrollment(participants)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Japan71152151374
Height
Height(cm)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Mean165.3 ± 8.89164.6 ± 8.82164.6 ± 9.12164.8 ± 8.94
Body Weight
Body Weight(kg)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Mean68.00 ± 13.70269.48 ± 13.07469.55 ± 14.92769.23 ± 13.943
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Mean24.72 ± 3.76425.61 ± 4.23125.52 ± 4.34425.41 ± 4.196
Duration of Type 2 Diabetes
Duration of Type 2 Diabetes(years)Alogliptin AloneAlogliptin + Metformin Hydrochloride QDAlogliptin + Metformin Hydrochloride BIDTotal
Mean7.73 ± 4.6667.02 ± 5.2577.04 ± 5.3807.16 ± 5.195

7 further baseline measures are reported on the registry.

08

Study locations

27 sites
  • Nagoya-shi, Aichi, Japan
  • Chiba-shi, Chiba, Japan
  • Fukuoka-shi, Fukuoka, Japan
  • Kitakyushu-shi, Fukuoka, Japan
  • Kurume-shi, Fukuoka, Japan
  • Aki-gun, Hiroshima, Japan
  • Hiroshima-shi, Hiroshima, Japan
  • Koga-shi, Ibaraki, Japan
  • Mito-shi, Ibaraki, Japan
  • Tushiura-shi, Ibaraki, Japan
  • Ushiku-shi, Ibaraki, Japan
  • Kanazawa-shi, Ishikawa, Japan
  • Takamatsu-chi, Kagawa, Japan
  • Sendai-shi, Miyagi, Japan
  • Ohita-shi, Ohita, Japan
  • Okinawa-shi, Okinawa, Japan
  • Shimajiri-gun, Okinawa, Japan
  • Kashiwara-shi, Osaka, Japan
  • Osaka-shi, Osaka, Japan
  • Hiki-gun, Saitama, Japan
  • Oyama-shi, Tochigi, Japan
  • Shimotsuke-shi, Tochigi, Japan
  • Koutoh-ku, Tokyo, Japan
  • Meguro-ku, Tokyo, Japan
  • Sagae-shi, Yamagata, Japan
  • Yamagata-shi, Yamagata, Japan
  • Yamaguchi-shi, Yamaguchi, Japan
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 28, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02068443
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Feb 21, 2014
Start date
Feb 2014
Primary completion
Feb 2015
Completion
Feb 2015
Results posted
Jun 6, 2016
Last update
Sep 28, 2023

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.

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