Efficacy and Safety of Alogliptin and Metformin Fixed-Dose Combination in Participants With Type 2 Diabetes

NCT01890122 | Completed Phase 3 Results

• 5 other identifiers: SYR-322MET_303U1111-1139-0497NMRR-12-799-12754CTR201302541036022140
• Study Type: interventional
• Target: 647
• Locations: 4 countries
• Sites: 45

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of alogliptin and metformin fixed-dose combination (FDC) as compared with alogliptin alone or metformin alone on Type 2 Diabetes Mellitus (T2DM).

Conditions

Diabetes Mellitus

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 (or Early Termination)

  The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 26 or early termination relative to baseline. Negative change indicates better glycemic control.

  Baseline and Week 26 (or Early termination)

Secondary Outcomes (13)

• Change From Baseline in HbA1c at Weeks 4, 8, 12, 16 and 20

  Baseline and Weeks 4, 8, 12, 16 and 20

• Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, 16, 20 and 26

  Baseline and Weeks 4, 8, 12, 16, 20 and 26

• Time to Hyperglycemic Rescue Event

  From the date of randomization through Week 26

• Percentage of Participants Requiring Hyperglycemic Rescue

  Baseline up to Week 26

• Percentage of Participants With Marked Hyperglycemia

  Baseline up to Week 26

Study Arms (4)

Metformin HCl 500 mg

ACTIVE COMPARATOR

Metformin hydrochloride (HCl) 500 mg, capsules, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; alogliptin and metformin HCl fixed dose combination (FDC) placebo-matching tablets, orally, twice a day for up to 26 weeks.

Drug: Metformin HCl; Drug: Alogliptin Placebo; Drug: Alogliptin and Metformin FDC Placebo

Alogliptin 12.5 mg

ACTIVE COMPARATOR

Alogliptin 12.5 mg, tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day; alogliptin and metformin HCl FDC placebo-matching tablets, orally, twice a day for up to 26 weeks.

Drug: Alogliptin; Drug: Metformin Placebo; Drug: Alogliptin and Metformin FDC Placebo

Alogliptin 12.5 mg + Metformin HCl 500 mg FDC

EXPERIMENTAL

Alogliptin 12.5 mg and metformin HCl 500 mg FDC, tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.

Drug: Alogliptin and Metformin Fixed-Dose Combination (FDC); Drug: Alogliptin Placebo; Drug: Metformin Placebo

Placebo

PLACEBO COMPARATOR

Alogliptin and metformin FDC placebo-matching tablets, orally, twice a day; alogliptin placebo-matching tablets, orally, twice a day; metformin placebo-matching capsules, orally, twice a day for up to 26 weeks.

Drug: Alogliptin Placebo; Drug: Metformin Placebo; Drug: Alogliptin and Metformin FDC Placebo

Interventions

Alogliptin DRUG

Alogliptin tablets

Also known as: SYR-322; Nesina

Alogliptin 12.5 mg

Metformin HCl DRUG

Metformin HCl capsules

Also known as: Glucophage

Metformin HCl 500 mg

Alogliptin and Metformin Fixed-Dose Combination (FDC) DRUG

Alogliptin and metformin FDC tablets

Also known as: Kazano

Alogliptin 12.5 mg + Metformin HCl 500 mg FDC

Alogliptin Placebo DRUG

Alogliptin placebo-matching tablets

Alogliptin 12.5 mg + Metformin HCl 500 mg FDC; Metformin HCl 500 mg; Placebo

Metformin Placebo DRUG

Metformin placebo-matching capsules

Alogliptin 12.5 mg; Alogliptin 12.5 mg + Metformin HCl 500 mg FDC; Placebo

Alogliptin and Metformin FDC Placebo DRUG

Alogliptin and metformin FDC placebo-matching tablets

Alogliptin 12.5 mg; Metformin HCl 500 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a historical diagnosis of Type 2 diabetes mellitus (T2DM).
• Male or female and aged 18 to 75 years, inclusive.
• Body mass index (BMI) between 20 and 45 kg/m\^2, inclusive.
• A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
• Is experiencing inadequate glycemic control defined as glycosylated hemoglobin (HbA1c) concentration between 7.5% and 10%, inclusive, and has been treated with diet and exercise for at least 2 months prior to Screening. (Exception: a participant who has received any other diabetic therapy for less than 7 days in total within the 2 months prior to the screening, can be included).
• If male, has a hemoglobin \>12 g/dL (\>120 g/L) at Screening or if female, has a hemoglobin \>10 g/dL (\>100 g/L) at Screening.
• If male, has a serum creatinine \<1.5 mg/dL at Screening or if female, has a serum creatinine \<1.4 mg/dL at Screening, and estimated glomerular filtration rate (eGFR) \>60 mL/min/1.73 m\^2 based on calculation using the Modification of Diet in Renal Disease (MDRD) at Screening.
• Willing and able to monitor their own blood glucose concentrations using a home glucose monitor and complete a subject diary.

You may not qualify if:

• Participated in another clinical study within 90 days prior to Screening.
• Received any investigational compound within 30 days prior to Randomization.
• Received a dipeptidyl peptidase-4 (DPP-4) inhibitor within 3 months prior to screening.
• History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• History of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery.
• History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
• Chronic pancreatitis and/or history of acute pancreatitis.
• Systolic blood pressure \>180 mm Hg and/or diastolic blood pressure \>110 mm Hg at Screening.
• History of any hemoglobinopathy or diagnosis of chronic anemia.
• New York Heart Association Class III or IV heart failure. (Participants who are stable at Class I or II and are currently treated, are candidates for the study.)
• History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
• History of any cancer, other than squamous cell or basal cell carcinoma of the skin, which has not been in full remission for at least 5 years prior to Screening. Participants with a history of treated cervical intraepithelial neoplasia \[CIN\] I or CIN II are allowed.
• Significant clinical sign or symptom of hepatopathy, acute or chronic hepatitis, human immunodeficiency virus or alanine aminotransferase (ALT) is 2.5 times above upper limit of normal value.
• History of angioedema in association with use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB).
• History of hypersensitivity or allergies to any DPP-4 inhibitor and/or metformin or related compounds.

Sponsors & Collaborators

• Takeda: lead

Study Sites (45)

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Beijing, Beijing Municipality, China

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Fuzhou, Fujian, China

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Xiamen, Fujian, China

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Guangzhou, Guangdong, China

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Nanning, Guangxi, China

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Guiyang, Guizhou, China

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Hengshui, Hebei, China

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Shijiazhuang, Hebei, China

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Shiyan, Hubei, China

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Wuhan, Hubei, China

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Changsha, Hunan, China

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Yueyang, Hunan, China

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Changzhou, Jiangsu, China

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Nanjing, Jiangsu, China

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Suzhou, Jiangsu, China

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Nanchang, Jiangxi, China

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Changchun, Jilin, China

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Shenyang, Liaoning, China

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Xi’an, Shanxi, China

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Chengdu, Sichuan, China

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Wenzhou, Zhejiang, China

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Beijing, China

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Shanghai, China

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Tianjin, China

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Johor Bahru, Johor, Malaysia

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Alor Star, Kedah, Malaysia

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Alor Star, Kedah Darul Aman, Malaysia

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Kubang Kerian, Kelantan, Malaysia

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Putrajaya, Kuala Lumpur, Malaysia

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Kampung Baharu Nilai, Negeri Sembilan, Malaysia

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Seremban, Negeri Sembilan, Malaysia

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Tampin, Negeri Sembilan, Malaysia

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Bagan Serai, Perak, Malaysia

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Ipoh, Perak, Malaysia

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Petaling Jaya, Selangor, Malaysia

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Shah Alam, Selangor, Malaysia

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Goyang-si, Gyeonggi-do, South Korea

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Seongnam-si, Gyeonggi-do, South Korea

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Suwon, Gyeonggi-do, South Korea

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Busan, South Korea

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Seoul, South Korea

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Kaohsiung City, Taiwan

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New Taipei City, Taiwan

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Taichung, Taiwan

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Taipei, Taiwan

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Related Links

• The Alogliptin-Metformin Fixed Dose Combination (KAZANO) were approved in the United States (US) on 25 January 2013.

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

alogliptin; Metformin

Condition Hierarchy (Ancestors)

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: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical 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: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: July 1, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 28, 2016
• Results First Posted: November 28, 2016

Record last verified: 2016-10

Locations

TW (4); KR (5); CN (24); MY (12)