Fasiglifam 25 mg BID vs 50 mg QD

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy of fasiglifam 25 mg twice daily (BID) and fasiglifam 50 mg once daily (QD) on glycemic control in adults with type 2 diabetes who are inadequately controlled on diet and exercise alone.

Detailed Description
-----------------
The drug being tested in this study is called fasiglifam. Fasiglifam is being tested to treat people who have diabetes. This study will look at glycemic control in people who take fasiglifam. The study will enroll approximately 400 patients. Participants will be randomly assigned (by chance) 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): Fasiglifam 25 mg twice a day Fasiglifam 50 mg once daily 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 twice each day throughout the study. All participants will be asked to record any time they have symptoms of hypoglycemia in a diary. This multi-center trial will be conducted worldwide. The overall time to participate in this study is 18 weeks. Participants will make 9 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.

Official Title
-----------------
A Phase 2 Randomized, Placebo-Controlled, Double-Blind Parallel-Group, Multicenter Study to Evaluate the Glycemic Effects and Safety of Fasiglifam 25 mg Twice Daily and 50 mg Once Daily on Glycemic Control in Subjects With Type 2 Diabetes

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Fasiglifam
* Drug: Placebo to fasiglifam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 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. Is male or female and 18 years of age or older with a historical diagnosis of Type 2 Diabetes Mellitus (T2DM). Has a glycosylated hemoglobin (HbA1c) level ≥7.0% and ≤10.0% and fasting plasma glucose (FPG) ≤270 mg/dL (15.0 mmol/L) at Screening Visit. Has been treated with diet and exercise but has not received treatment with antidiabetic agents within 12 weeks prior to Screening Visit (Exception: if a patient has received other antidiabetic therapy for ≤7 days in total within the 2 months prior to Screening Visit). Has a body mass index (BMI) ≤45 kg/m^2 at Screening. If regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening Visit. However, as needed (PRN) use of prescription or over-the-counter medications is allowed at the discretion of the investigator. 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. A female of childbearing potential who is sexually active with a non-sterilized 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. Exclusion Criteria: Has received any investigational compound within 30 days prior to Screening Visit or has received an investigational anti-diabetic drug within the 3 months prior to Screening Visit. Was randomized into a previous fasiglifam study. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. Has donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study. Has a hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening. Has a systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening Has a history of cancer that has been in remission for <5 years prior to Screening. A history of basal cell carcinoma or stage 1 squamous cell carcinoma of the skin is allowed. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2.0× upper limit of normal (ULN) at Screening. Has a total bilirubin level greater than the ULN at Screening. Exception: if a patient has documented Gilbert's syndrome the patient will be allowed with an elevated bilirubin level per the investigator's discretion. Has a serum creatinine ≥1.5 mg/dL (≥133μmol/L) (males) and ≥1.4 mg/dL (≥124 μmol/L) (females) and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 at Screening. Has uncontrolled thyroid disease as determined by the investigator. Has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening. Had gastric banding, or gastric bypass surgery within one year prior to Screening. Has a known history of infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus. Had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal electrocardiogram (ECG), cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening. Has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any component of fasiglifam. Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within 2 years prior to Screening. Received excluded medications prior to Screening Visit or is expected to receive excluded medication. If female, is pregnant (confirmed by laboratory testing, ie, serum/urine human chorionic gonadotropin (hCG), in females of childbearing potential) or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. The subject is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available. The subject has any other physical or psychiatric disease or condition that in the judgment of the investigator may affect life expectancy or may make it difficult to successfully manage and follow the subject according to the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Fasiglifam placebo-matching tablets, orally, twice daily for up to 12 weeks. | Drug: Placebo to fasiglifam<br>* Fasiglifam placebo-matching tablets<br>|
| Experimental: Fasiglifam 25 mg BID<br>Fasiglifam 25 mg tablets, orally, twice daily (BID) for up to 12 weeks. | Drug: Fasiglifam<br>* Fasiglifam tablets<br>* Other names: TAK-875;|
| Experimental: Fasiglifam 50 mg QD +Placebo QD<br>Fasiglifam 50 mg tablets, orally once daily (QD) and fasiglifam placebo-matching tablets, orally, once daily for up to 12 weeks. | Drug: Fasiglifam<br>* Fasiglifam tablets<br>* Other names: TAK-875;Drug: Placebo to fasiglifam<br>* Fasiglifam placebo-matching tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 12. | 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 12 or final visit relative to baseline. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 | The change between the FPG value collected at week 12 or final visit relative to baseline. | Baseline and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug therapy