Comparison of TAK-875 to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

Glycemic Control Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-875 25 mg and 50 mg Compared to Placebo and Sitagliptin 100 mg When Used in Combination With Metformin in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01549964
• Other study ID #: TAK-875_302
• Secondary ID: 2011-001752-10U1
• Status: Terminated
• Phase: Phase 3
• First received: March 6, 2012
• Last updated: January 23, 2014
• Start date: May 2012
• Est. completion date: May 2016

Study information

• Verified date: January 2014
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBulgaria: Bulgarian Drug AgencyCzech Republic: State Institute for Drug ControlItaly: The Italian Medicines AgencyMalaysia: Ministry of HealthSouth Korea: Korea Food and Drug Administration (KFDA)Croatia: Ministry of Health and Social CareHungary: National Institute of PharmacySlovakia: State Institute for Drug ControlAustralia: Department of Health and Ageing Therapeutic Goods AdministrationThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of 2 doses of TAK-875 (25 mg and 50 mg), once daily (QD), plus metformin compared to placebo plus metformin and sitagliptin plus metformin on lowering blood sugar.

Description:

TAK-875 is being developed at Takeda Global Research and Development, Inc. as an adjunct to diet and exercise to improve glycemic control in participants with Type 2 Diabetes Mellitus (T2DM) whose blood glucose level is inadequately controlled with metformin.

This study will evaluate the efficacy of TAK-875 (25 mg and 50 mg) plus metformin compared to placebo plus metformin and sitagliptin plus metformin on glycemic control as measured by change from baseline in glycosylated hemoglobin (HbA1c) over a 24-week Treatment Period. Participants completing the 24-week Treatment Period may enter an optional 80-week extension period for a total of 104 weeks of treatment.

Due to potential concerns about liver safety, on balance, the benefits of treating patients with fasiglifam (TAK-875) do not outweigh the potential risks.

For this reason, Takeda has decided voluntarily to terminate the development activities for fasiglifam.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 916
• Est. completion date: May 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The participant is male or female and 18 years of age or older with a historical diagnosis of type II diabetes mellitus.

2. The participant meets one of the following criteria:

1. The participant has an HbA1c level =7.5 and <10.5%, and has been on a stable daily dose of =1500 mg (or documented maximum tolerated dose [MTD]) of metformin for at least 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;

2. The participant has an HbA1c level =7.5 and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this participant will have their metformin dose immediately increased to =1500 mg (or MTD) for an 8-week Titration Period according to Study Schedule B. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level =7.5 and <10.5%.

3. The participant has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for =7 days within the 2 months prior to Screening).

4. The participant has a body mass index (BMI) =45 kg/m² at Screening.

5. Participants regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator.

6. The participant is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations and complete subject diaries.

Exclusion Criteria:

1. The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.

2. Hemoglobin =12 g/dL (=120 g/L) for males and =10 g/dL (=100 g/L) for females at Screening Visit.

3. The participant has systolic blood pressure =160 mm Hg or diastolic pressure =95 mm Hg at Screening Visit. (If the participant meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement.)

4. The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.

5. The participant has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening.

6. The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glycemic Control

Intervention

Drug:
• TAK-875
TAK-875 tablets
• Sitagliptin
Sitagliptin tablets
• Placebo
Placebo-matching tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Croatia,  Czech Republic,  Hungary,  Italy,  Korea, Republic of,  Malaysia,  Slovakia,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Glycosylated Hemoglobin (HbA1c)	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 24 or final visit relative to baseline.	Baseline and Week 24.	No
Secondary	Incidence of HbA1c <7%	Incidence of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected over 24 weeks.	24 Weeks.	No
Secondary	Change from Baseline in Fasting Plasma Glucose (FPG)	The change between FPG collected at week 24 or final visit relative to baseline.	Baseline and Week 24.	No