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Type 2 Diabetes MellitusPhase 3NCT02068443

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 study testing Alogliptin and Metformin hydrochloride in people with Type 2 Diabetes Mellitus, run by Takeda at 27 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 more about this study

Who is it for?
Ages 20 to 74 years
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Alogliptin and Metformin hydrochloride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
374 participants
Where
27 sitesJapan
Study dates
Feb 2014to Feb 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

Japan27 sites

  • Study site

    Aki-gun, Hiroshima

  • Study site

    Chiba, Chiba

  • Study site

    Fukuoka, Fukuoka

  • Study site

    Hiki-gun, Saitama

  • Study site

    Hiroshima, Hiroshima

  • Study site

    Kanazawa, Ishikawa-ken

  • Study site

    Kashiwara-shi, Osaka

  • Study site

    Kitakyushu-shi, Fukuoka

  • Study site

    Koga-shi, Ibaraki

  • Study site

    Koutoh-ku, Tokyo

  • Study site

    Kurume-shi, Fukuoka

  • Study site

    Meguro-ku, Tokyo

  • Study site

    Mito, Ibaraki

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Ohita-shi, Ohita

  • Study site

    Okinawa-shi, Okinawa

  • Study site

    Osaka, Osaka

  • Study site

    Oyama-shi, Tochigi

  • Study site

    Sagae-shi, Yamagata

  • Study site

    Sendai, Miyagi

  • Study site

    Shimajiri-gun, Okinawa

  • Study site

    Shimotsuke-shi, Tochigi

  • Study site

    Takamatsu-chi, Kagawa-ken

  • Study site

    Tushiura-shi, Ibaraki

  • Study site

    Ushiku-shi, Ibaraki

  • Study site

    Yamagata, Yamagata

  • Study site

    Yamaguchi, Yamaguchi

Other trials in Japan

About this study

Official title: A Phase 3 Multicenter, Randomized, Double-blind, Parallel-group, Comparative Study When Metformin Hydrochloride 500 mg is Added on to SYR-322 25 mg in Type 2 Diabetic Patients

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.

Being tested
Alogliptin, Metformin hydrochloride, Metformin hydrochloride Placebo
Keywords
Drug therapy
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlogliptinDrug

    Also called SYR-322, Nesina®

    Alogliptin tablets

  • Metformin hydrochlorideDrug

    Also called Glycoran®

    Metformin hydrochloride tablets

  • Metformin hydrochloride PlaceboDrug

    Metformin hydrochloride placebo-matching tablets

Study groups in NCT02068443
Study groupRoleWhat they receive
Alogliptin AloneActive comparatorAlogliptin 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.
Receives: Drug: Alogliptin; Drug: Metformin hydrochloride Placebo
Alogliptin + Metformin Hydrochloride QDExperimentalAlogliptin 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.
Receives: Drug: Alogliptin; Drug: Metformin hydrochloride; Drug: Metformin hydrochloride Placebo
Alogliptin + Metformin Hydrochloride BIDActive comparatorAlogliptin 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.
Receives: Drug: Alogliptin; Drug: Metformin hydrochloride; Drug: Metformin hydrochloride Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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]).

    Measured: 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".

    Measured: Baseline and Weeks 12 and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
374 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02068443
Sponsor's protocol ID
SYR-322-MET/CCT-001
Other IDs
JapicCTI-132377, U1111-1151-6515
Status last verified
Aug 2023
First submitted
19 Feb 2014
Last updated
28 Sep 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alogliptin and Metformin hydrochloride in people with Type 2 Diabetes Mellitus, run by Takeda at 27 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) National Glycohemoglobin Standardization Program (NGSP) at the End of Treatment (EOT) Period (time frame: Baseline and End of Treatment (EOT) (Up to Week 24)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02068443.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.

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Clinical Trial NCT02068443 | AzTrials