Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type II Diabetes Mellitus
Condition: Type II Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Subetta; Placebo
Intervention description: Each Subetta tablet contains a mixture of affinity purified polyclonal antibodies to β-subunit of the rINS (6 mg) and antibodies to eNOS (6 mg) in released-active form produced by the patented technology in accordance with the applicable European Pharmacopeia requirements.
Standard therapy of type II diabetes mellitus + Subetta (1 tablet 4 times a day) for 36 weeks.
Subetta: oral administration, per 1 intake - 1 tablet (keep in the mouth until complete dissolution, not at mealtime).; Placebo (identical to Subetta in shape and taste tablet containing exсipients). Standard therapy of type II diabetes mellitus + Placebo (1 tablet 4 times a day) for 36 weeks.
Placebo: oral administration, per 1 intake - 1 tablet (keep in the mouth until complete dissolution, not at mealtime).
Phase: Phase 4
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 190.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Combined Treatment of Patients With Type II Diabetes Mellitus

Summary:

      The purpose of this study is:

        -  to assess clinical efficacy of Subetta in the combined treatment of type II diabetes
           mellitus;

        -  to assess safety of Subetta in the combined treatment of type II diabetes mellitus.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosed type II diabetes mellitus (according to WHO criteria, 1999 - 2006).

          2. Patient's age from 18 to 65 years inclusive.

          3. Level of glycosylated hemoglobin 7.0- 10.0 %.

          4. Dose of basal insulin ≥10 units/day combined with metformin or with metformin and
             sulfonylurea derivatives during not less than 3 months prior to inclusion in the
             trial.

          5. Body mass index ≥25.0 and ≤40.0kg/m^2.

          6. Constant body weight (without fluctuations > 10% during not less than 3 months prior
             to inclusion in the trial).

          7. Glomerular filtration rate ≥ 60 ml/ min/1.73m^2.

          8. Stable dose of basal insulin for the last 3 months.(Permissible fluctuations are
             ±10%.)

          9. Usage of contraceptive methods by both gender patients of reproductive age during the
             trial and within 30 days after ending the participation in the trial.

         10. Availability of signed patient information sheet (Informed Consent form) for
             participation in the clinical trial.

        Exclusion Criteria:

          1. Acute diabetes mellitus complications for 3 months prior to inclusion in the trial
             (diabetic ketoacidosis, hyperosmolar hyperglycemic state, lacticemia, severe
             hypoglycemia and hypoglycemic coma).

          2. Diabetic retinopathy, preproliferative, proliferative or terminal stages (based on the
             results of oculist examination during screening period or 6 months prior to the
             trial).

          3. Diabetic nephropathy, proteinuria stage, chronic kidney disease on 3, 4 or 5 stage.

          4. Diabetic microangiopathy:

               -  ishemic heart disease (medical history of a sudden coronary death with successful
                  reanimation, medical history of myocardial infarction, stable exertional angina
                  III or IV FC; unstable angina; postinfarction cardiosclerosis; chronic heart
                  failure III or IV FC);

               -  cerebrovascular diseases (medical history of acute cerebrovascular accident;
                  progressive vascular leukoencephalopathy; vascular dementia);

               -  chronic obliterative peripheral vascular diseases (clinically significant);

               -  diabetic neuroosteoarthropathy;

               -  diabetic foot (clinically significant).

          5. Heart rhythm disorder:

               -  II-III atrioventricular block;

               -  sick sinus syndrome;

               -  long QT interval syndrome;

               -  complete left bundle branch block;

               -  block of 2/3 bundle branches;

               -  WPW syndrome;

               -  ventricular arrhythmia of III grade according Laun-Wolf;

               -  paroxysmal supraventricular tachycardia;

               -  paroxysmal/recurrent ventricular tachycardia;

               -  atrial flutter and fibrillation;

               -  ventricular flutter and fibrillation;

               -  heart pacemaker implant.

          6. Uncontrolled arterial hypertension characterized by the following blood tension
             values: systolic blood pressure over 160 mm Hg and/or diastolic blood pressure over
             100 mm Hg.

          7. Severe concomitant pathology including clinically significant cardio- vascular
             diseases of III - IV functional class (according to New York Heart Association
             classification, 1964), nervous and endocrine system diseases, including morbid obesity
             (body mass index≥40.0 kg/m^2), renal insufficiency, liver failure.

          8. Medical history of pancreatectomy or transplantation of pancreatic/islet cells.

          9. Medical history of renal transplantation.

         10. Malignant neoplasms/suspected malignant neoplasms.

         11. Exacerbations or decompensation of chronic diseases affecting a patient's ability to
             participate in the clinical trial.

         12. The results of analysis of liver enzymes (alanine aminotransferase, aspartate
             aminotransferase) more than threefold exceeding of upper limit of normal values.

         13. Level of fasting triglycerides >5.64 mmol/L.

         14. Medical history of bariatric surgical operations.

         15. Medical history of polyvalent allergy

         16. Allergy/ intolerance to any of the components of medications used in the treatment.

         17. Intake of medicines listed in the section "Prohibited concomitant treatment" for 3
             months prior to the inclusion in the trial.

         18. Pregnancy, breast-feeding.

         19. Drug addiction, alcohol usage in the amount exceeding 2 units of alcohol per day.

         20. Mental disorders of a patient.

         21. Night work.

         22. Participation in other clinical trials in the course of 3 months prior to the
             inclusion in the trial.

         23. Patients, who from the investigator's point of view, will fail to comply with the
             observation requirements of the trial or with the intake regimen of the investigated
             medicines.

         24. Other factors impeding patient's participation in the trial (for example, planned
             business trips or journeys).

         25. Patient is related to the research personnel of the investigative site, who are
             directly involved in the trial or are the immediate relative of the researcher. The
             immediate relative includes husband/wife, parents, children or brothers (or sisters),
             regardless of whether they are natural or adopted.

         26. Patient works for OOO "NPF "Materia Medica Holding" (i.e. is the company's employee,
             temporary contract worker or appointed official responsible for the carrying out the
             research) or the immediate relative.