A Phase 3, Randomized, Double-blind, Parallel-group, Comparative Study and a Phase 3, Multicenter, Open-label, Long-term Study of SYR-472 (25 mg) in Patients With Type 2 Diabetes Mellitus Complicated by Severe Renal Impairment or End-stage Renal Disease

NCT02512068 | Completed Phase 3 Results

• 3 other identifiers: SYR-472-3003U1111-1172-1511JapicCTI-152970
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 49

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of trelagliptin when administered at a dose of 25 mg once weekly using placebo as a control in patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one antidiabetic drug in addition to diet and/or exercise therapy (if given); and to evaluate the long-term efficacy and safety of trelagliptin when administered at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal disease.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in HbA1c at the End of Treatment Period I

  Baseline (Week 0) and end of Treatment Period I (Up to Week 12)

• Number of Participants Who Had One or More Treatment Emergent Adverse Event (TEAE) Before the Start of Study Drug Administration in Treatment Period II

  An Adverse Event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a drug (including the study drug). It does not necessarily have to have a causal relationship with this treatment (including the study drug). An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug (including the study 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. Reported data is the number of participants reporting one or more TEAEs that occurred before the start of Treatment Period II in each group.

  Up to Week 12

• Number of Participants Who Had One or More TEAE Occurred After 1st Dose of Trelagliptin 25 mg Tablet

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a drug (including the study drug). It does not necessarily have to have a causal relationship with this treatment (including the study drug). An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug (including the study drug), whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. As to collect the safety data of long-term treatment with the active drug widely, the number of participants reporting one or more TEAEs that occurred after 1st dose of trelagliptin 25 mg, that is events in Period I and II for "Trelagliptin 25 mg" group and events in Period II for "Placebo and Trelagliptin 25 mg" group, was analyzed.

  Up to Week 54

Secondary Outcomes (7)

• Changes From Baseline in HbA1c

  Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)

• Number of Participants Achieving <6.0%, <7.0%, and <8.0% HbA1c at the End of Treatment Period I and Period II

  At the end of Treatment Period I (Up to Week 12) and Period II (Up to Week 52)

• Change From Baseline in Fasting Plasma Glucose

  Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)

• Change From Baseline in Glycoalbumin

  Baseline (Week 0) and Week 2, 4, 8, 12, and End of Treatment Period I (up to Week 12) and Period II (up to Week 52)

• Numbers of Participants With TEAE Related to Vital Signs Before the Start of Study Drug Administration in Treatment Period II

  Up to Week 12

Study Arms (2)

Trelagliptin 25 mg

EXPERIMENTAL

Trelagliptin 25 mg tablet, orally, once weekly before breakfast for up to Week 52 (Period I + II)

Drug: Trelagliptin 25 mg

Placebo and Trelagliptin 25 mg

EXPERIMENTAL

Placebo tablet, orally, once weekly before breakfast for up to Week 12 (Period I), followed by trelagliptin 25 mg tablet, orally, once weekly before breakfast for up to Week 52 (Period II)

Drug: Trelagliptin 25 mg; Drug: Placebo

Interventions

Trelagliptin 25 mg DRUG

Trelagliptin 25 mg Tablets

Also known as: SYR-472

Placebo and Trelagliptin 25 mg; Trelagliptin 25 mg

Placebo DRUG

Placebo Tablets

Placebo and Trelagliptin 25 mg

Eligibility Criteria

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

You may qualify if:

• The participant has a diagnosis of type 2 diabetes mellitus.
• The participant has a fasting C-peptide value 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 hemoglobin value of 10.0 g/dL 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 7.0% or higher but less than 10.0% at Week -2 of the screening period. For participants undergoing hemodialysis (with End-stage Renal Disease \[ESRD\]), those with a glycoalbumin value of 20% or higher could be enrolled even if their HbA1c value is below 7.0% at Week -2 of the screening period.
• \<HbA1c value of 7.0% 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%\* of the HbA1c value at the start of the screening period (Week -6).
• \<For participants undergoing hemodialysis (with ESRD), glycoalbumin value of 20% or higher and HbA1c value of below 7.0% at Week -2 of the screening period\> The participant has a glycoalbumin difference between the start of the screening period (Week -6) and Week -2 of the screening period within 10.0%\* of the glycoalbumin value at the start of the screening period (Week -6).
• \*: rounded to one decimal place
• The participant has been on a fixed diet and/or exercise therapy (if any) for at least 6 weeks prior to the start of the screening period (Week -6).
• The participant meets any of the following:
• The participant has not received any antidiabetic medications (including insulin preparations) from at least 6 weeks prior to the start of the screening period (Week -6).
• The participant is being treated with one oral hypoglycemic drug\* starting from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen.
• \*: any one of the following medications: mitiglinide calcium hydrate, repaglinide, acarbose, miglitol, or voglibose
• The participant is being treated with one insulin preparation\*\* starting from at least 6 weeks prior to the start of the screening period (Week -6) at a fixed dose and regimen (≤40 units/day) of the insulin preparation.
• Any one of the following insulin monotherapies: mixed (short-acting or rapid-acting insulin containing no more than 30% volume), intermediate-acting, or long-acting soluble insulin preparations
• The participant is not undergoing hemodialysis or peritoneal dialysis and has severe renal impairment \[creatinine clearance (Ccr) \<30 mL/min at the start of the screening period (Week -6)\], or the participant is undergoing hemodialysis and has end-stage renal failure.

You may not qualify if:

• The participant has clinically evident 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 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 severe ketosis, diabetic coma or precoma, type 1 diabetes, severe infection, before or after surgery, or severe external trauma.
• The participant has hemoglobinopathy (sickle cell disease, thalassemia, etc.).
• The participant experienced hypoglycemia (participants with a blood glucose value 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 inadequately controlled hypertension.
• For participants who are being treated with one antidiabetic agent, the participant was using at least two antidiabetic therapies on the 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 participant has malignancies.
• The participant has a history of hypersensitivity or allergies to dipeptidyl peptidase 4 (DPP-4) inhibitors.
• The participant has a history of gastrectomy or small intestinal resection.
• The participant is a habitual drinker and consumes 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.
• The participant is required to take excluded medications during the study period.
• The participant has previously received trelagliptin.
• The participant received any other investigational products (including study drugs in a post-marketing clinical study) within 12 weeks prior to the start of the screening period.

Sponsors & Collaborators

• Takeda: lead

Study Sites (49)

Unknown Facility

Anjo, Aichi-ken, Japan

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Kasukabe, Aichi-ken, Japan

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Nagoya, Aichi-ken, Japan

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Toyohashi, Aichi-ken, Japan

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Yatomi, Aichi-ken, Japan

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Asahi, Chiba, Japan

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Kisarazu, Chiba, Japan

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Yotsukaidō, Chiba, Japan

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Imabari, Ehime, Japan

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Matsuyama, Ehime, Japan

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Niihama, Ehime, Japan

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Chikushino-shi, Fukuoka, Japan

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Kasuga, Fukuoka, Japan

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Kasuya-gun, Fukuoka, Japan

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Kitakyushu, Fukuoka, Japan

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Munakata, Fukuoka, Japan

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Tajimi, Gifu, Japan

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Takasaki, Gunma, Japan

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Fukuyama, Hiroshima, Japan

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Chitose, Hokkaido, Japan

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Himeji, Hyōgo, Japan

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Takarazuka, Hyōgo, Japan

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Mito, Ibaragi, Japan

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Sakai, Ibaragi, Japan

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Fujisawa, Kanagawa, Japan

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Kamakura, Kanagawa, Japan

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Kawasaki, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Sendai, Miyagi, Japan

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Nakano, Nagano, Japan

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Ueda, Nagano, Japan

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Kasaoka, Okayama-ken, Japan

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Setouchi, Okayama-ken, Japan

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Fukaya, Saitama, Japan

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Kumagaya, Saitama, Japan

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Hamamatsu, Shizuoka, Japan

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Yoshinogawa, Tokushima, Japan

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Hachiōji, Tokyo, Japan

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Itabashi-ku, Tokyo, Japan

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Kunitachi, Tokyo, Japan

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Uozu, Toyama, Japan

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Shimonoseki, Yamaguchi, Japan

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Ube, Yamaguchi, Japan

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Akita, Japan

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Kumamoto, Japan

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Nagano, Japan

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Niigata, Japan

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Osaka, Japan

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Yamagata, 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: July 28, 2015
• First Posted: July 30, 2015
• Study Start: August 7, 2015
• Primary Completion: April 24, 2018
• Study Completion: April 24, 2018
• Last Updated: December 12, 2023
• Results First Posted: November 4, 2019

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

JP (49)