Overview

Condition type 2 diabetes mellitus
Treatments syr-472 25 mg, placebo + syr-472 25 mg
Phase phase 3
Sponsor Takeda
Start date August 2015
End date April 2018
Trial size 106 participants
Trial identifier NCT02512068, JapicCTI-152970, SYR-472-3003, U1111-1172-1511

Summary

The purpose of this study is to evaluate the efficacy and safety of SYR-472 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 failure and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one other antidiabetic drug in addition to diet and/or exercise therapy (if given); and to evaluate the long-term efficacy and safety of SYR-472 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 failure.

Recruiting in the following locations…

United States No locations recruiting
Other Countries Japan

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
One tablet of SYR-472 25 mg orally once weekly before breakfast (in both Treatment Period I and II)
syr-472 25 mg
SYR-472 25 mg Tablets
(Experimental)
Treatment Period I: One placebo tablet orally once weekly before breakfast Treatment Period II: One tablet of SYR-472 25 mg orally once weekly before breakfast
placebo + syr-472 25 mg
Placebo Tablets + SYR-472 25 mg Tablets

Primary Outcomes

Measure
Change in HbA1c from baseline at the end of the Treatment Period I (12 Week)
time frame: Up to Week 12
Number of participants who experience at least 1 treatment-emergent adverse event
time frame: Up to Week 52

Secondary Outcomes

Measure
Proportion of participants achieving <6.0%, <7.0%, and <8.0% HbA1c at the end of Treatment Period I (12 Week) and at the end of Treatment Period II (52 Week)
time frame: Week 12 and Week 52

Eligibility Criteria

Male or female participants at least 20 years old.

Inclusion Criteria: 1. The participant has a diagnosis of type 2 diabetes mellitus. 2. 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. 3. 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. 4. The participant has an HbA1c value of 7.0% or higher but less than 10.0% at Week -2 of the screening period, unless the participant who is undergoing hemodialysis (Patients with End-stage Renal Failure) has a HbA1c value of less than 7.0% at Week -2 and glycated albumin value of 20% or higher. 5. The participant has an HbA1c value of 7.0% or higher but less than 10.0% at Week -2 - 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). The participant who is undergoing hemodialysis (Patients with End-stage Renal Failure) has an HbA1c value of less than 7.0% at Week -2 and glycated albumin value of 20% or higher. - The difference of the glycated albumin values from the start of the screening period (Week -6) to Week -2 is 10%* or less of the glycated albumin values at Week -6. *: rounded to one decimal place 6. The participant has been on a fixed diet and/or exercise therapy (if given) from at least 6 weeks prior to the start of the screening period (Week -6). 7. 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 (rapid-acting or short-acting insulin containing no more than 30% volume), intermediate-acting, or long-acting soluble insulin preparations 8. 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. 9. In the opinion of the investigator or subinvestigator, the initiation of hemodialysis or peritoneal dialysis at least within 12 weeks after starting the investigational product is not expected. [in cases where the participant is not undergoing hemodialysis or peritoneal dialysis (patients with severe renal impairment)] 10. The participant has been undergoing hemodialysis starting from at least 6 months prior to informed consent and, in the opinion of the investigator or subinvestigator, the participant is clinically stable. [in cases where the participant is undergoing hemodialysis (patient with end-stage renal failure)] 11. The participant is male or female and is aged 20 years or older at the time of informed consent. 12. 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. 13. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements. 14. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures. Exclusion Criteria: 1. The participants has clinically evident hepatic impairment [e.g., AST or 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]. 2. 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). 3. The participant has severe ketosis, diabetic coma or pre coma, type 1 diabetes, severe infection, before or after surgery, or severe external injury. 4. The participant has hemoglobinopathy (sickle cell disease, thalassemia, etc.). 5. 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). 6. The participant has inadequately controlled hypertension. 7. 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). 8. The participant has malignancies. 9. The participant has a history of hypersensitivity or allergies to dipeptidyl peptidase 4 (DPP-4) inhibitors. 10. The participant has a history of gastrectomy or small intestinal resection. 11. The participant is a habitual drinker and consumes a daily average of more than 100 mL of alcohol. 12. The participant has a history of drug abuse (defined as the use of an illegal drug) or alcohol dependence. 13. The participant is required to take excluded medications during the study period. 14. The participant has received SYR-472 in a previous clinical study. 15. 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. 16. The participant is participating in other clinical studies at the time of informed consent. 17. If female, the participant is pregnant or lactating or intending to become pregnant from the time of informed consent to within 1 month after the end of the study; or intending to donate ova during such time period. 18. The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. 19. The participant is hospitalized during the screening period or is deemed as requiring hospitalization during the study period by the investigator or sub-investigator, unless the hospitalization is for short-term evaluations including complete health checkups or shunt (including shunt maintenance). 20. The participant is deemed ineligible for the study for any other reason by the investigator or sub-investigator.

Additional Information

Official title A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Comparative Study and a Phase 3, Multicenter, Open-label, Long-term Study to Evaluate the Safety and Efficacy of SYR-472 When Orally 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 Failure
Description This is a phase 3, multicenter, randomized, double-blind, parallel-group, comparative study (Treatment Period I) and a phase 3, multicenter, open-label, long-term study (Treatment Period II) using placebo as a control to evaluate the efficacy and safety of SYR-472 when administered orally at a dose of 25 mg once weekly to patients with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal failure and inadequate glycemic control despite diet and/or exercise therapy (if given) or despite treatment with one other antidiabetic drug in addition to diet and/or exercise therapy (if given).
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Takeda.