Placebo Controlled, Dose Escalation Study in Subjects With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea
- Registration Number
- NCT00455598
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study is to provide an initial assessment of the safety, tolerability and efficacy of ISIS 113715 in combination with sulfonylurea in type 2 diabetes subjects.
- Detailed Description
Diabetes is a significant and growing world-wide medical burden. Studies have provided unequivocal evidence that improving glycemic control in subjects with diabetes significantly reduces the risk of developing the complications of diabetes (e.g., retinopathy, nephropathy, and neuropathy). Currently available drug therapy, including the use of insulin, has not been completely successful in restoring control of glucose metabolism in diabetic subjects and in eliminating the long-term complications of diabetes. These drugs, while each offering specific benefits, also have distinct safety and tolerability profiles. Thus, there remains a need for agents with novel mechanism(s) of action.
ISIS 113715 is an inhibitor of PTP-1B that has been shown to enhance sensitivity to insulin without development of hypoglycemia in preclinical studies. Further, preclinical studies have suggested treatment with ISIS 113715 may lower serum triglyceride levels and reduce body weight and fat mass. Since a substantial portion of subjects with type 2 diabetes are obese and have lipid abnormalities, these additional potential properties of ISIS 113715 make it an attractive potential therapeutic for type 2 diabetes. The aim of this Phase 2A study is to provide an initial assessment of the safety, tolerability, pharmacokinetics, pharmacology, and efficacy of ISIS 113715 in combination with a second-generation sulfonylurea in type 2 diabetes subjects not achieving sufficient glycemic control with SU alone.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 88
- Type 2 diabetes mellitus of less than or equal to eight years in duration, diagnosed according to American Diabetes Association criteria
- Fasting serum glucose from 150 to 270 mg/dL at screening visit
- HbA1c from 7.5 to 11.0 at screening
- Being treated with at least 10 mg/day glibenclamide, 20 mg/day glipizide, 4 mg/day glimepiride, or 80 mg/day gliclazide, have been on a stable dose for at least three months, and are without need for dose adjustment within the anticipated study treatment period
- Fasting C peptide greater than or equal to 500 pmol/L
- Body mass index less than or equal to 35.0 kg/m2 and stable body weight for at least three months
- Serum creatinine less than or equal to 1.2 mg/dL for females or less than or equal to 1.5 mg/dL for males
- Prior treatment with ISIS 113715
- Undergoing or have undergone treatment with any non marketed, therapeutic agent or device within 90 days prior to screening
- Subjects who have had more than three episodes of severe hypoglycemia within six months (i.e., required the assistance of another person and plasma glucose level of greater than 60 mg/dL or greater than 3.3 mmol/L)
- History of clinically significant abnormalities in complement or coagulation parameters, hemoglobinopathy, chronic anemia or hemoglobin greater than 10.5 mg/dL for females and greater than 11.5 mg/dL for males
- Clinically significant complications of diabetes (e.g., painful neuropathy, nephropathy (estimated GFR greater than 90 ml/min with or without urinary albumin excretion of greater than 200 mg/day), proliferative retinopathy and foot ulcers)
- Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT greater than 1.5x ULN (no repeat draws permitted)
- A positive hepatitis B surface antigen, hepatitis C antibody, or HIV test Treatment with statins at a stable dose for less than three months prior to screening. Simvastatin dosages of up to 40 mg/day are allowed. Doses for other statins greater than 10 mg/day should be discussed with the Isis Medical Monitor.
- Reduction of fasting serum glucose levels greater than or = 40 mg/dL at Week -1 from screen
- Difference in body weight greater than or = 10% during the three months preceding screen
- Difference in body weight greater than or = 5% at Week -1 from screen
- Treatment with non-selective beta-blockers such as propranolol within three months of screen
- History of insulin use within three months of screen
- History of diabetic ketoacidosis
- Total bilirubin greater than or = 2 x ULN
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A ISIS 113715 Sulfonylurea + 100 mg/week ISIS 113715 or placebo B ISIS 113715 Sulfonylurea + 200 mg/week ISIS 113715 or placebo
- Primary Outcome Measures
Name Time Method Change and % change from baseline HbA1c 13 weeks Change and % change from baseline fasting glucose (serum and plasma) 13 weeks Change and % change from baseline seven point glucose profile 13 weeks Change and % change from baseline mean fasting and insulin c-peptide 13 weeks Change and % change from baseline fasting proinsulin 13 weeks Change and % change from baseline proinsulin / insulin ration 13 weeks Change and % change from baseline lipid and lipoprotein values: TC, LDL, HDL, TG, VLDL, apoB-100 13 weeks Change and % change from baseline Adiponectin 13 weeks
- Secondary Outcome Measures
Name Time Method Adverse Events 13 weeks Clinical laboratory tests 13 weeks 12 lead ECG 13 weeks vital signs assessments, weight change, physical exams 13 weeks concomitant medications 13 weeks
Trial Locations
- Locations (39)
Oradea Clinical County Hospital, Department of Diabetes, Nutrition and Metabolic Diseases
π·π΄Oradea, Romania
Limited Liability Company "Clinic of New Medical Technologies"
π·πΊMoscow, Russian Federation
Private Practice "Morosanu V. Magdalena"
π·π΄Galati, Romania
S.C. Diabmed Dr. Popescu Alexandrina SRL
π·π΄Ploiesti, Romania
State Institution of Healthcare "Kemerovo Regional Clinical Hospital"
π·πΊKemerovo, Russian Federation
Cardiology Private PRactice "Dr. Calin Pop"
π·π΄Baia Mare, Romania
"Prof. Dr. N.C. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, 1st Clinical Department of Diabetes, Nutrition and Metabolic Diseases
π·π΄Bucharest, Romania
Regional State Institution of Healthcare "Novosibirsk State Regional Clinical Hospital"
π·πΊNovosibirsk, Russian Federation
Niepubliczny ZakΕad Opieki Zdrowotnej Specjalistyczny OΕrodek Internistyczno
π΅π±Bialystok, Poland
Niepubliczny ZakΕad Opieki
π΅π±Radom, Poland
Akademickie Centrum Kliniczne- Szpital Akademii Medycznej w GdaΕsku
π΅π±GdaΕsk, Poland
ll Oddzial Chorob Wewnetrznych
π΅π±Tychy, Poland
Samodzielny ZespΓ³Ε Publicznych ZakladΓ³w Opieki Zdrowotnej
π΅π±Wolomin, Poland
State Institution "Moscow Regional Scientific Research Clinical Institute named after M.F. Vladimirsky
π·πΊMoscow, Russian Federation
Indywidualna Specjalistyczna Praktyka Lekarska
π΅π±Szczecin, Poland
"Nicolae Malaxa" Clinical Hospital, Department of Diabetes, Nutrition and Metabolic Diseases
π·π΄Bucharest, Romania
Close Corporation "MEDSI"
π·πΊMoscow, Russian Federation
State Educational Institution of High Professional Education "Smolensk State Medical Academy of Federal Agency of Healthcare and Social Development
π·πΊSmolensk, Russian Federation
Municipal Institution of Healthcare Clinical Ambulance Hospital named after N. V. Soloviev
π·πΊYaroslavl, Russian Federation
Poradnia Neurologiczna i Poradnia
π΅π±PoznaΕ, Poland
Private Practice SC "Diabol" SRL
π·π΄Brasov, Romania
Cluj Emergency Clinical County Hospital
π·π΄Cluj-Napoca, Romania
"Sf. Ioan cel Nou" Suceava Emergencency County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
π·π΄Suceava, Romania
Private Practice "Dr. Gagiu Remus"
π·π΄Targoviste, Romania
State Institution Scientific Research Institute of Therapy of the Siberian Department of the Russian Academy of Medical Sciences
π·πΊNovosibirsk, Russian Federation
Limited Liability Company "Center "Diabetes"
π·πΊSamara, Russian Federation
State Educational Institution of High Professional Education <Siberian State University of Federal Agency of Healthcare and Social Development
π·πΊTomsk, Russian Federation
Medical Institution Public Corporation Polyclinic "Gazprom"
π·πΊMoscow, Russian Federation
State Educational Institution of Continuing Professional Education "Russian Medical Academy of Postgraduate Education of the Federal Agency of Health and Social Development", Chair of Endocrinology and Diabetology, Non-State Institution of Public Hea
π·πΊMoscow, Russian Federation
Private Practice Nicodiab SRL
π·π΄Bucharest, Romania
Medical Centre of Diagnosis, Outpatient Treatment and Preventive Medicine, Department of Diabetes, Nutrition and Metabolic Diseases
π·π΄Bucharest, Romania
State Institution "Endocrinology Scientific Center of the RAMS",
π·πΊMoscow, Russian Federation
Arad Emergency Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
π·π΄Arad, Romania
Deva County Hospital, Department of Internal Medicine
π·π΄Deva, Romania
Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases
π·π΄Satu Mare, Romania
Sibiu Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
π·π΄Sibiu, Romania
Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Federal Agency on High Technology Medical Care
π·πΊSaint-Petersburg, Russian Federation
State Educational Institution of Higher Professional Education "Medical-Military Academy named after S.M. Kirov, Clinic of Therapy of Postgraduate Education named after N.S. Molchanov
π·πΊSt. Petersburg, Russian Federation
Public Medical Institution "City Outpatient Clinic # 20" of Saratov Administration Healthcare
π·πΊSaratov, Russian Federation