Diabetes
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the effect of TAK-875 (fasiglifam) in combination with sitagliptin on glycemic control in adults with type 2 diabetes.
Detailed description
The drug being tested in this study is called TAK-875 (fasiglifam). Fasiglifam is being tested to treat people who have type 2 diabetes mellitus and are currently taking sitagliptin (with or without metformin). This study will evaluate glycemic control in people who take fasiglifam plus sitagliptin compared with placebo plus sitagliptin. The study will enroll approximately 390 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need; all participants will be on 100 mg sitagliptin and may or may not be on metformin background treatment): * fasiglifam 25 mg * fasiglifam 50 mg * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient All participants will be asked to take one tablet at the same time each day throughout the study. This multi-centre trial will be conducted in North America and Latin America. The overall time to participate in this study is approximately 38 weeks. Participants will make 15 visits to the clinic. 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.
Interventions
DRUGPlacebo
TAK-875 placebo-matching tablets
DRUGTAK-875
TAK-875 tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. 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. 3. The participant is male or female and aged 18 years or older with a historical diagnosis of T2DM. 4. The participant meets one of the following criteria: * The participant has an HbA1c between 7.5% and 10.5%, inclusive and has been taking a stable dose of sitagliptin 100 mg for at least 8 weeks, with or without metformin, prior to the Screening Visit. A participant who is taking metformin must have received a stable daily dose (≥1500 mg or documented maximum tolerated dose \[MTD\]) for at least 8 weeks before Screening. This participant will enter the 2-week single-blind Placebo Run-In Period according to Study Schedule A, or; * The participant has an HbA1c between 7.5% and 10.5%, inclusive and has been taking any other DPP-IV inhibitor (with or without metformin) for at least 8 weeks prior to the Screening Visit. A participant who is taking metformin must have received a stable daily dose (≥1500 mg or documented MTD) for at least 8 weeks before Screening. This participant will enter the 8-week Switching Period according to Study Schedule B. Following this 8-week period, the participant must qualify for all Inclusion/
Exclusion criteria
prior to entering the 2-Week Placebo Run-in Period by completing the Week ( 3) procedures including having an HbA1c level between 7.5% and 10.5%. Note: An enrollment cap may be applied to ensure no more than approximately 20% of randomized participants are receiving a DPP-IV inhibitor without metformin at baseline. 5. The participant has had no treatment with antidiabetic agents other than DPP-IV inhibitors and metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 consecutive days within the 2 months prior to Screening). 6. The participant has a body mass index (BMI) ≤45 kg/m2 at Screening. 7. 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 medication is allowed at the discretion of the investigator. 8. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 30 days after the last dose of study drug. 9. 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 participant diaries.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 24 | Baseline and Week 24 | The change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HbA1c <7% | Week 24 | — |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | The change between the fasting plasma glucose values collected at Week 24 relative to baseline. |
Countries
Argentina, Peru, United States
Participant flow
Recruitment details
Participants took part in the study at 49 investigative sites in the United States from 01 April 2013 to 12 March 2014.
Pre-assignment details
Participants with historical diagnosis of type 2 diabetes who were inadequately controlled while on sitagliptin 100 milligram(mg) (with/without metformin) or on Dipeptidyl peptidase-4 inhibitor other than sitagliptin(with/without metformin) therapy enrolled in 1 of 3, placebo; fasiglifam 25 mg once daily (QD); fasiglifam 50 mg QD treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Fasiglifam placebo-matching tablets, orally, once daily and sitagliptin 100 mg, tablets, orally, once daily with or without metformin greater than or equal to (\>=) 1500 mg, tablets, orally, once daily for up to 24 weeks. | 30 |
| Fasiglifam 25 mg QD Fasiglifam 25 mg, tablets, orally, once daily and sitagliptin 100 mg, tablets, orally, once daily with or without metformin \>=1500 mg, tablets, orally, once daily for up to 24 weeks. | 31 |
| Fasiglifam 50 mg QD Fasiglifam 50 mg, tablets, orally, once daily and sitagliptin 100 mg, tablets, orally, once daily with or without metformin \>=1500 mg, tablets, orally, once daily for up to 24 weeks. | 29 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Study terminated by sponsor | 25 | 28 | 25 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Fasiglifam 25 mg QD | Fasiglifam 50 mg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 57.0 Years STANDARD_DEVIATION 10.45 | 52.4 Years STANDARD_DEVIATION 11.61 | 55.2 Years STANDARD_DEVIATION 8.57 | 54.8 Years STANDARD_DEVIATION 10.38 |
| Age, Customized >= 65 years | 8 Participants | 4 Participants | 5 Participants | 17 Participants |
| Age, Customized Less than (<) 65 years | 22 Participants | 27 Participants | 24 Participants | 73 Participants |
| Baseline Glycosylated Hemoglobin (HbA1c) Category >= 8.5% | 14 Participants | 15 Participants | 14 Participants | 43 Participants |
| Baseline Glycosylated Hemoglobin (HbA1c) Category < 8.5 percent (%) | 16 Participants | 16 Participants | 15 Participants | 47 Participants |
| Body Mass Index | 34.49 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.623 | 32.12 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.664 | 33.10 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.315 | 33.23 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.286 |
| Duration of Diabetes | 9.291 years STANDARD_DEVIATION 8.039 | 8.690 years STANDARD_DEVIATION 6.18 | 6.406 years STANDARD_DEVIATION 4.39 | 8.154 years STANDARD_DEVIATION 6.444 |
| Height | 168.3 centimeter (cm) STANDARD_DEVIATION 9.26 | 169.0 centimeter (cm) STANDARD_DEVIATION 10.02 | 166.8 centimeter (cm) STANDARD_DEVIATION 10.76 | 168.0 centimeter (cm) STANDARD_DEVIATION 9.96 |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants | 22 Participants |
| Race/Ethnicity, Customized More than 1 race (multiracial) | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 24 Participants | 20 Participants | 24 Participants | 68 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 26 Participants | 26 Participants | 77 Participants |
| Region of Enrollment | 30 Participants | 31 Participants | 29 Participants | 90 Participants |
| Sex/Gender, Customized Female | 14 Participants | 13 Participants | 16 Participants | 43 Participants |
| Sex/Gender, Customized Male | 16 Participants | 18 Participants | 13 Participants | 47 Participants |
| Smoking Classification Current smoker | 7 Participants | 5 Participants | 1 Participants | 13 Participants |
| Smoking Classification Ex-smoker | 5 Participants | 7 Participants | 6 Participants | 18 Participants |
| Smoking Classification Never smoked | 18 Participants | 19 Participants | 22 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 30 | 10 / 31 | 15 / 29 |
| serious Total, serious adverse events | 0 / 30 | 1 / 31 | 0 / 29 |
Outcome results
Primary
Change From Baseline in HbA1c at Week 24
The change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to baseline.
Time frame: Baseline and Week 24
Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of double blind study medication and who had a baseline and at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Week 24 | Baseline (n= 26, 31, 27) | 8.39 Percentage of glycosylated haemoglobin | Standard Deviation 0.766 |
| Placebo | Change From Baseline in HbA1c at Week 24 | Change at Week 24 (n= 2, 4, 2) | 0.25 Percentage of glycosylated haemoglobin | Standard Deviation 0.495 |
| Fasiglifam 25 mg QD | Change From Baseline in HbA1c at Week 24 | Baseline (n= 26, 31, 27) | 8.46 Percentage of glycosylated haemoglobin | Standard Deviation 0.932 |
| Fasiglifam 25 mg QD | Change From Baseline in HbA1c at Week 24 | Change at Week 24 (n= 2, 4, 2) | -0.80 Percentage of glycosylated haemoglobin | Standard Deviation 0.883 |
| Fasiglifam 50 mg QD | Change From Baseline in HbA1c at Week 24 | Baseline (n= 26, 31, 27) | 8.52 Percentage of glycosylated haemoglobin | Standard Deviation 0.956 |
| Fasiglifam 50 mg QD | Change From Baseline in HbA1c at Week 24 | Change at Week 24 (n= 2, 4, 2) | -1.85 Percentage of glycosylated haemoglobin | Standard Deviation 0.495 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
The change between the fasting plasma glucose values collected at Week 24 relative to baseline.
Time frame: Baseline and Week 24
Population: FAS included all randomized participants who received at least 1 dose of double blind study medication and who had a baseline and at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline (n= 29, 31, 28) | 193.76 milligram per deciliter (mg/dL) | Standard Deviation 50.09 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change at Week 24 (n= 2, 2, 2) | 30.50 milligram per deciliter (mg/dL) | Standard Deviation 55.861 |
| Fasiglifam 25 mg QD | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline (n= 29, 31, 28) | 184.52 milligram per deciliter (mg/dL) | Standard Deviation 45.126 |
| Fasiglifam 25 mg QD | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change at Week 24 (n= 2, 2, 2) | -31.50 milligram per deciliter (mg/dL) | Standard Deviation 16.263 |
| Fasiglifam 50 mg QD | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline (n= 29, 31, 28) | 185.96 milligram per deciliter (mg/dL) | Standard Deviation 53.767 |
| Fasiglifam 50 mg QD | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change at Week 24 (n= 2, 2, 2) | -85.50 milligram per deciliter (mg/dL) | Standard Deviation 23.335 |
Secondary
Percentage of Participants With HbA1c <7%
Time frame: Week 24
Population: Due to the relatively limited enrollment and follow-up at the time of study termination, the analysis of percentage of participants with HbA1c \<7% at Week 24 was not performed.