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

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

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

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo/Metformin; Drug: SP2086 50 mg b.i.d/Metformin; Drug: SP2086 50 mg q.d./Metformin

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. <80% or >120% compliance with placebo treatment during the run-in period
2. 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:

1. Type 1 diabetes, single gene mutation diabetes, diabetes caused by pancreatic damage and secondary diabetes, such as caused by Cushing's syndrome or acromegaly
2. a history of hypertension, and after antihypertensive treatment, systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg
3. a history of acute and chronic pancreatitis or pancreatic injury that may lead to high risk of pancreatitis
4. serious haematological diseases or other diseases leading to hemolyze and Red Blood Cell unstable (malaria、haemolytic anaemia eg. )
5. other endocrine diseases, for example hyperthyroidism、hypothyroidism、hypercortisolism、multiple endocrine neoplasia and so on
6. 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
7. 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
8. Acute metabolic complications (ketoacidosis, lactic acidosis or hyperosmolar coma), unstable proliferative retinopathy or macular degeneration within 6 months prior to randomization
9. Severe trauma or acute infection that may affect blood glucose control within 4 weeks prior to randomization
10. Severe chronic gastrointestinal disease or therapy that may affect drug absorption, such as gastrointestinal surgery
11. 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:

1. Aspartate Aminotransferase or alanine aminotransferase ≥ 2.0× upper normal limit(UNL) , and/or total bilirubin ≥ 2.0 × UNL also review confirmed within 3 days;
2. Triglyceride>5.64mmol/L（500mg/dl）；
3. serum creatinine to exceed the normal range
4. thyroid stimulating hormone to exceed the normal range, and have clinical significance
5. blood amylase o exceed the normal range, and have clinical significance
6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo/Metformin	Drug: Placebo/Metformin; 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
Experimental: SP2086 (50mg b.i.d)/Metformin	Drug: SP2086 50 mg b.i.d/Metformin; 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
Experimental: SP2086 (50mg q.d.)/Metformin	Drug: SP2086 50 mg q.d./Metformin; 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

What is the study measuring?

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
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 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
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 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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): January 1, 2014
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 25, 2013

Study Record Updates

• Last Update Posted (Estimate): October 25, 2013
• Last Update Submitted That Met QC Criteria: October 22, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Phase III; combination therapy; SP2086
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: HR-SP2086-302