A Phase 4, Randomized, Double-blind, Parallel-group, Comparative Study and a Phase 4, Open-label, Long-term Study of SYR-472 (100 mg) in Combination With Insulin in Patients With Type 2 Diabetes

NCT02324569 | Completed Phase 3 Results

• 2 other identifiers: SYR-472/CCT-101U1111-1164-8291
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 65

Brief Summary

The purposes of this study is to evaluate the efficacy and safety of SYR-472 when administered at a dose of 100 mg once weekly as an add-on to insulin therapy compared with placebo in patients with type 2 diabetes mellitus and inadequate glycemic control despite treatment with insulin preparations in addition to diet and/or exercise therapy; and to evaluate the long-term efficacy and safety of SYR-472 when administered at a dose of 100 mg once weekly as an add-on to insulin therapy in patients with type 2 diabetes mellitus and inadequate glycemic control despite treatment with insulin preparations in addition to diet and/or exercise therapy.

Conditions

Type 2 Diabetes Mellitus

Keywords

Pharmacological therapy

Outcome Measures

Primary Outcomes (2)

• Change in HbA1c From Baseline at the End of Treatment Period I (End of Treatment Period I - End of the Screening Period)

  End of the screening period (Week 0) and End of Treatment Period I (Up to Week 12)

• Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs) That Occurred Before Start of Treatment Period II

  Reported data is the number of participants reporting one or more TEAEs that occurred before start of Treatment Period II in Treatment Group I and Treatment Group II.

  Up to Week 12

Secondary Outcomes (8)

• Change From Baseline in HbA1c

  Baseline and Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, End of Treatment Period I (Up to Week 12) and End of Treatment Period II (Up to Week 52)

• Change From Baseline in Fasting Plasma Glucose

  Baseline and Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 53, End of Treatment Period I (Up to Week 12) and End of Treatment Period II (Up to Week 52)

• Change From Baseline in Plasma Glucose Measured by the Meal Tolerance Test in Treatment Period I

  Pre-meal and 0.5, 1, and 2 hr after-meal at Week 0 and 0.5, 1, and 2 hr after-meal at the End of Treatment Period I (Up to Week 12)

• Number of Participants With Markedly Abnormal Values of Vital Signs Before Start of Treatment Period II

  Up to Week 12

• Number of Participants With Markedly Abnormal Values of ECG Parameters Before Start of Treatment Period II

  Up to Week 12

Study Arms (2)

Treatment Group I

EXPERIMENTAL

One tablet of SYR-472 100 mg orally once weekly before breakfast

Drug: SYR-472

Treatment Group II

EXPERIMENTAL

One tablet of SYR-472 100 mg orally or one placebo tablet orally once weekly before breakfast

Drug: SYR-472; Drug: Placebo

Interventions

SYR-472 DRUG

SYR-472 tablets

Treatment Group I; Treatment Group II

Placebo DRUG

Placebo tablets

Treatment Group II

Eligibility Criteria

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

You may qualify if:

• Participant eligibility is determined according to the following criteria:
• The participant has a diagnosis of type 2 diabetes mellitus.
• The participant has a fasting C-peptide level of 0.6 ng/mL or higher at the start of the screening period (Week -6) and Week -2 of the screening period.
• The participant has a Haemoglobin A1c (HbA1c) value of 7.5% or higher but less than 10.0% at Week -2 of the screening period.
• The participant has an HbA1c value difference between the start of the screening period (Week -6) and Week -2 of the screening period within 10.0%\* (\* rounded to one decimal place) of the HbA1c value at the start of the screening period (Week -6).
• The participant has been on a fixed diet and/or exercise therapy (if any) from at least 6 weeks prior to the start of the screening period (Week -6).
• The participant is being treated with insulin preparations alone (≥8 units/day and ≤40 units/day) \*\* from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen of the insulin preparation.
• The participant on any one of the following insulin monotherapies: mixed (rapid-acting or short-acting insulin containing no more than 30% volume), intermediate-acting, or long-acting soluble insulin preparations
• The participant is deemed appropriate for treatment with a combination of insulin and another antidiabetic drug at the start of the screening period (Week -6) by the investigator or subinvestigator.
• The participants with controlled and stable blood pressure will not need any change in the dose of antihypertensive drugs (including discontinuation and suspension) or additional antihypertensive drugs during the study period as assessed by the investigator or subinvestigator.
• The participant is male or female and aged 20 years or older at the time of informed consent.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent until one month after the end of the study.
• In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.

You may not qualify if:

• Any participant who meets any of the following criteria will not qualify for entry into the study:
• The participants has clinical manifestations of hepatic impairment \[e.g., Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥2.5 times the upper limit of normal or total bilirubin of ≥2.0 mg/dL at the start of the screening period (Week -6) or at Week -2 of the screening period\].
• The participant has moderate or severe renal impairment or end-stage renal failure \[e.g., creatinine clearance (Ccr) \<50 mL/min at the start of the screening period (Week -6) or Week -2 of the screening period\].
• The participant has any serious cardiac diseases, cerebrovascular disorders, or serious pancreatic or hematological diseases (e.g., participants who require inpatient treatment or are hospitalized for treatment within 24 weeks prior to the start of the screening period).
• The participant has, in the judgment of the investigator or subinvestigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at the start of the screening period (Week - 6) or Week -2 of the screening period.
• The participant has a systolic blood pressure of 180 mmHg or higher or a diastolic blood pressure of 110 mmHg or higher during the screening period.
• The participant is on at least two antidiabetic therapies other than one insulin preparation one day before 6 weeks prior to the start of the screening period (Week -6) (43 days prior to the start of the screening period).
• The participants altered the dose and regimen of their insulin preparation within 6 weeks prior to the start of the screening period or during the screening period.
• The participant experienced hypoglycemia (participants with a blood glucose level of ≤70 mg/dL or hypoglycemic symptoms) within 6 weeks prior to the start of the screening period or during the screening period (at least twice per week).
• The participant has a fasting blood glucose level of 240 mg/dL or higher at the start of the screening period (Week -6) or at Week -2 of the screening period.
• The participant has malignancies.
• The participant has a history of hypersensitivity or allergies to dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin preparations.
• The participant has a history of gastrectomy or small intestinal resection.
• The participant is habitual drinker consuming a daily average of more than 100 mL of alcohol.
• The participant has a history of drug abuse (defined as the use of an illegal drug) or alcohol dependence.

Sponsors & Collaborators

• Takeda: lead

Study Sites (65)

Unknown Facility

Nagoya, Aichi-ken, Japan

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Hirosaki, Aomori, Japan

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Kurume, Fukuoka, Japan

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Sapporo, Hokkaido, Japan

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Koga, Ibaragi, Japan

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Mito, Ibaragi, Japan

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Naka, Ibaragi, Japan

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Tsuchiura, Ibaragi, Japan

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Ushiku, Ibaragi, Japan

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Kanazawa, Ishikawa-ken, Japan

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Satsumakawauchi, Kagoshima-ken, Japan

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Chigasaki, Kanagawa, Japan

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Fujisawa, Kanagawa, Japan

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Sendai, Miyagi, Japan

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Hirakata, Osaka, Japan

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Kashihara, Osaka, Japan

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Suita, Osaka, Japan

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Ageo, Saitama, Japan

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Sangou, Saitama, Japan

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Hamamatsu, Shizuoka, Japan

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Shimada, Shizuoka, Japan

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Koyama, Tochigi, Japan

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Shimono, Tochigi, Japan

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Chiyoda-ku, Tokyo, Japan

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Nerima-ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Suginami-ku, Tokyo, Japan

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Tama, Tokyo, Japan

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Shimonoseki, Yamaguchi, Japan

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Shunann, Yamaguchi, Japan

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Ageo, Japan

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Aomori, Japan

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Chiba, Japan

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Chigasaki, Japan

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Chiyoda-ku, Japan

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Fujisawa, Japan

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Fukuoka, Japan

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Hamamatsu, Japan

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Hirakata, Japan

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Hirosaki, Japan

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Kagoshima, Japan

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Kanazawa, Japan

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Kashiwara, Japan

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Koga, Japan

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Koyama, Japan

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Kumamoto, Japan

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Kurume, Japan

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Kyoto, Japan

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Mito, Japan

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Nagoya, Japan

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Naka, Japan

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Nerima-ku, Japan

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Osaka, Japan

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Sangō, Japan

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Satsumakawauchi, Japan

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Sendai, Japan

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Shimada, Japan

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Shimono, Japan

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Shimonoseki, Japan

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Shinjuku-ku, Japan

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Shizuoka, Japan

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Suginami-ku, Japan

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Tama, Japan

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Toyama, Japan

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Tsuchiura, Japan

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

trelagliptin

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical 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: December 19, 2014
• First Posted: December 24, 2014
• Study Start: December 27, 2014
• Primary Completion: December 28, 2016
• Study Completion: December 28, 2016
• Last Updated: December 12, 2023
• Results First Posted: February 11, 2019

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

JP (65)