Placebo Controlled, Dose Escalation Study in Subjects With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea

NCT ID: NCT00455598

Last Updated: 2009-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2009-05-31

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A

Sulfonylurea + 100 mg/week ISIS 113715 or placebo

Group Type: PLACEBO_COMPARATOR

ISIS 113715

Intervention Type: DRUG

doses of 100 and 200 mg per week

B

Sulfonylurea + 200 mg/week ISIS 113715 or placebo

Group Type: PLACEBO_COMPARATOR

ISIS 113715

Intervention Type: DRUG

doses of 100 and 200 mg per week

Interventions

ISIS 113715

doses of 100 and 200 mg per week

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Isis Pharmaceuticals

Principal Investigators

Isis Pharmaceuticals

Role: STUDY_CHAIR

Ionis Pharmaceuticals, Inc.

Locations

Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno

Bialystok, , Poland

Akademickie Centrum Kliniczne- Szpital Akademii Medycznej w Gdańsku

Gdansk, , Poland

Poradnia Neurologiczna i Poradnia

Poznan, , Poland

Niepubliczny Zakład Opieki

Radom, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska

Szczecin, , Poland

ll Oddzial Chorob Wewnetrznych

Tychy, , Poland

Samodzielny Zespół Publicznych Zakladów Opieki Zdrowotnej

Wołomin, , Poland

Arad Emergency Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases

Arad, , Romania

Cardiology Private PRactice "Dr. Calin Pop"

Baia Mare, , Romania

Private Practice SC "Diabol" SRL

Brasov, , Romania

Private Practice Nicodiab SRL

Bucharest, , Romania

Medical Centre of Diagnosis, Outpatient Treatment and Preventive Medicine, Department of Diabetes, Nutrition and Metabolic Diseases

Bucharest, , Romania

"Prof. Dr. N.C. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, 1st Clinical Department of Diabetes, Nutrition and Metabolic Diseases

Bucharest, , Romania

"Nicolae Malaxa" Clinical Hospital, Department of Diabetes, Nutrition and Metabolic Diseases

Bucharest, , Romania

Cluj Emergency Clinical County Hospital

Cluj-Napoca, , Romania

Deva County Hospital, Department of Internal Medicine

Deva, , Romania

Private Practice "Morosanu V. Magdalena"

Galati, , Romania

Oradea Clinical County Hospital, Department of Diabetes, Nutrition and Metabolic Diseases

Oradea, , Romania

S.C. Diabmed Dr. Popescu Alexandrina SRL

Ploieşti, , Romania

Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases

Satu Mare, , Romania

Sibiu Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases

Sibiu, , Romania

"Sf. Ioan cel Nou" Suceava Emergencency County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases

Suceava, , Romania

Private Practice "Dr. Gagiu Remus"

Târgovişte, , Romania

State Institution of Healthcare "Kemerovo Regional Clinical Hospital"

Kemerovo, , Russia

State Institution "Endocrinology Scientific Center of the RAMS",

Moscow, , Russia

Medical Institution Public Corporation Polyclinic "Gazprom"

Moscow, , Russia

Close Corporation "MEDSI"

Moscow, , Russia

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

Moscow, , Russia

State Institution "Moscow Regional Scientific Research Clinical Institute named after M.F. Vladimirsky

Moscow, , Russia

Limited Liability Company "Clinic of New Medical Technologies"

Moscow, , Russia

Regional State Institution of Healthcare "Novosibirsk State Regional Clinical Hospital"

Novosibirsk, , Russia

State Institution Scientific Research Institute of Therapy of the Siberian Department of the Russian Academy of Medical Sciences

Novosibirsk, , Russia

Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Federal Agency on High Technology Medical Care

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Limited Liability Company "Center "Diabetes"

Samara, , Russia

Public Medical Institution "City Outpatient Clinic # 20" of Saratov Administration Healthcare

Saratov, , Russia

State Educational Institution of High Professional Education "Smolensk State Medical Academy of Federal Agency of Healthcare and Social Development

Smolensk, , Russia

State Educational Institution of High Professional Education <Siberian State University of Federal Agency of Healthcare and Social Development

Tomsk, , Russia

Municipal Institution of Healthcare Clinical Ambulance Hospital named after N. V. Soloviev

Yaroslavl, , Russia

Countries

Poland; Romania; Russia

Other Identifiers

EudraCT No: 2006-005718-11

Identifier Type: -

Identifier Source: secondary_id

113715-CS14

Identifier Type: -

Identifier Source: org_study_id