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

NCT02068443 | Completed Phase 3 Results

• 3 other identifiers: SYR-322-MET/CCT-001JapicCTI-132377U1111-1151-6515
• Study Type: interventional
• Target: 374
• Locations: 1 country
• Sites: 27

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Drug therapy

Outcome Measures

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.

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

Secondary Outcomes (9)

• Change From Baseline in HbA1c (NGSP)

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

• HbA1c (NGSP)

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

• Percentage of Participants Achieving Target HbA1c (NGSP) Levels at the EOT Period

  Baseline and EOT (Up to Week 24)

• Change From Baseline in Fasting Blood Glucose

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

• Fasting Blood Glucose

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

Study Arms (3)

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

Interventions

Alogliptin DRUG

Alogliptin tablets

Also known as: SYR-322, Nesina®

Alogliptin + Metformin Hydrochloride BID; Alogliptin + Metformin Hydrochloride QD; Alogliptin Alone

Metformin hydrochloride DRUG

Metformin hydrochloride tablets

Also known as: Glycoran®

Alogliptin + Metformin Hydrochloride BID; Alogliptin + Metformin Hydrochloride QD

Metformin hydrochloride Placebo DRUG

Metformin hydrochloride placebo-matching tablets

Alogliptin + Metformin Hydrochloride BID; Alogliptin + Metformin Hydrochloride QD; Alogliptin Alone

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (27)

Unknown Facility

Nagoya, Aichi-ken, Japan

Location

Unknown Facility

Chiba, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Kitakyushu-shi, Fukuoka, Japan

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Kurume-shi, Fukuoka, Japan

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Aki-gun, Hiroshima, Japan

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Hiroshima, Hiroshima, Japan

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Koga-shi, Ibaraki, Japan

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Mito, Ibaraki, Japan

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Tushiura-shi, Ibaraki, Japan

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Ushiku-shi, Ibaraki, Japan

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Kanazawa, Ishikawa-ken, Japan

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Takamatsu-chi, Kagawa-ken, Japan

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Sendai, Miyagi, Japan

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Ohita-shi, Ohita, Japan

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Okinawa-shi, Okinawa, Japan

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Shimajiri-gun, Okinawa, Japan

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Kashiwara-shi, Osaka, Japan

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Osaka, Osaka, Japan

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Hiki-gun, Saitama, Japan

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Oyama-shi, Tochigi, Japan

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Shimotsuke-shi, Tochigi, Japan

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Koutoh-ku, Tokyo, Japan

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Meguro-ku, Tokyo, Japan

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Sagae-shi, Yamagata, Japan

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Yamagata, Yamagata, Japan

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Unknown Facility

Yamaguchi, Yamaguchi, Japan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

alogliptin; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Takeda (Note: This product was divested to Teijin Pharma Limited in 2023)

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2014
• First Posted: February 21, 2014
• Study Start: February 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: September 28, 2023
• Results First Posted: June 6, 2016

Record last verified: 2023-08

Locations

JP (27)