A Phase III Study of SP2086 in Combination With Metformin in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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SP2086 is a new dipeptidy1 peptidase(DPP)-4 inhibitors. This study aims to evaluate the efficacy and safety of SP2086 in combination therapy with Metformin in patients with Type 2 Diabetes Mellitus in Metformin monotherapy Who Have Inadequate Glycemic Control

Official Title
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A Multicenter Randomized, Double-blind, Placebo Controlled ,Parallel Group ,Phase III Study to Access the Efficacy and Safety of SP2086 in Combination Therapy With Metformin in Patients With Type 2 Diabetes Patients

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Placebo/Metformin
* Drug: SP2086 50 mg b.i.d/Metformin
* Drug: SP2086 50 mg q.d./Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with type 2 diabetes mellitus subject on metformin monotherapy with stable dose ≥1500mg/d for ≥8 weeks 7.5% ≤HbA1C ≤11.0% at screening,7.0% ≤HbA1C ≤10.5% after run-in Body Mass Index: ≥19 and ≤35 kg/m2 Exclusion Criteria: <80% or >120% compliance with placebo treatment during the run-in period Patients used the following drugs or therapies prior to randomization: 1) Somatropin therapy within 6 months prior to randomization 2) History of drug or alcohol abuse within 6 months prior to randomization 3) Participate in clinical trials of any drugs or medical devices within 3 months prior to randomization 4) Receive corticosteroids long-term (more than 7 consecutive days) oral, non-gastrointestinal administration or intra-articular administration within 2 months prior to randomization 5) Weight control drugs administration or Surgeries resulting in weight instability within 2 months prior to randomization 6) In investigator's opinion, patients used any drugs that interfere with assessment of the investigational product, or produce vital organs toxicity 4. Patients with history of the following diseases or proof prior to randomization: Type 1 diabetes, single gene mutation diabetes, diabetes caused by pancreatic damage and secondary diabetes, such as caused by Cushing's syndrome or acromegaly a history of hypertension, and after antihypertensive treatment, systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg a history of acute and chronic pancreatitis or pancreatic injury that may lead to high risk of pancreatitis serious haematological diseases or other diseases leading to hemolyze and Red Blood Cell unstable (malaria、haemolytic anaemia eg. ) other endocrine diseases, for example hyperthyroidism、hypothyroidism、hypercortisolism、multiple endocrine neoplasia and so on Any organ system tumors except the local skin basal cell carcinoma that have been treated or not been treated within 5 years prior to randomization, regardless of whether there is evidence of local recurrence or metastasis ; a history or family history of medullary carcinoma of thyroid ; a history of multiple endocrine neoplasia Decompensated heart failure (NYHA class III and IV), unstable angina, stroke or transient ischemic attack, myocardial infarction, persistence and clinical significance arrhythmia, coronary artery bypass grafting or percutaneous coronary intervention within 6 months prior to randomization Acute metabolic complications (ketoacidosis, lactic acidosis or hyperosmolar coma), unstable proliferative retinopathy or macular degeneration within 6 months prior to randomization Severe trauma or acute infection that may affect blood glucose control within 4 weeks prior to randomization Severe chronic gastrointestinal disease or therapy that may affect drug absorption, such as gastrointestinal surgery With a history of mental/emotional disorder that would interfere with the subject's participation in the study. 5. Patients with any laboratory parameters meet the following criteria prior to randomization: Aspartate Aminotransferase or alanine aminotransferase ≥ 2.0× upper normal limit(UNL) , and/or total bilirubin ≥ 2.0 × UNL also review confirmed within 3 days; Triglyceride>5.64mmol/L（500mg/dl）； serum creatinine to exceed the normal range thyroid stimulating hormone to exceed the normal range, and have clinical significance blood amylase o exceed the normal range, and have clinical significance In investigator's opinion, any significant laboratory abnormalities of clinical significance value that interfere with assessment of this study. 6. At Screening patients not installed pacemaker with II or III degree atrioventricular block, long QT syndrome or QT corrected > 500 ms 7. Patients who received blood transfusions or blood donation≥ 400 mL or severe blood loss at least 400 mL within 8 weeks prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo/Metformin<br> | Drug: Placebo/Metformin<br>* Run in period ：placebo and metformin 500 mg t.i.d for 6 weeks Phase A : Placebo and metformin 500 mg t.i.d for 24 weeks Phase B : SP2086 50 mg b.i.d and metformin 500 mg t.i.d for 28 weeks<br>|
| Experimental: SP2086 (50mg b.i.d)/Metformin<br> | Drug: SP2086 50 mg b.i.d/Metformin<br>* Run-in period: placebo and Metformin 500 mg t.i.d for 6weeks Phase A:SP2086 50 mg b.i.d and Metformin 500 mg t.i.d for 24 weeks Phase B:SP2086 50 mg b.i.d and Metformin 500 mg t.i.d for 28 weeks<br>|
| Experimental: SP2086 (50mg q.d.)/Metformin<br> | Drug: SP2086 50 mg q.d./Metformin<br>* Run-in period: placebo and Metformin 500 mg t.i.d for 6 weeks Phase A:SP2086 50 mg q.d and Metformin 500 mg t.i.d for 24 weeks Phase B:SP2086 50 mg q.d and Metformin 500 mg t.i.d for 28 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week24 | A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent | baseline, week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Less Than (<) 6.5% or <7% HbA1c Levels |  | week24, 52 | 
| Change From Baseline in fasting plasma glucose (FPG) at Week 24,52 | Change from baseline at Week 24,52 is defined as Week 24 ,52 FPG minus Week 0 FPG | Weeks 0-24-52 | 
| Change From Baseline in 2-hour Post-meal Glucose (2-hr PMG) at Week 24 | Change from baseline at Week 24 is defined as Week 24 2-hr PMG minus Week 0 2-hr PMG | Weeks 0-24 | 
| Change From Baseline in HbA1c at Week 52 | A1C is measured as a percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the Week 0 HbA1c percent | week 52 | 
| Change From Baseline in lipid at Week 4、8、12、24、38、52 |  | Week 4、8、12、24、38、52 | 
| Change From Baseline in Body Weight at Week 4,8,12、24、38、52 |  | Week 4、8、12、24、38、52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SP2086, Phase III, combination therapy