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

Sponsored by:	Isis Pharmaceuticals
Information provided by:	Isis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00455598

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: ISIS 113715	Phase II

MedlinePlus related topics: Diabetes

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Placebo Control, Randomized, Safety/Efficacy Study, Treatment
Official Title:	A Phase 2, Multi Center, Randomized, Double Blind, Placebo Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, PK, & Activity of ISIS 113715 Administered Weekly in Subjects With Type 2 DM Treated w/ Sulfonylurea

Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:

Change and % change from baseline HbA1c [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline fasting glucose (serum and plasma) [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline seven point glucose profile [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline mean fasting and insulin c-peptide [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline Adiponectin [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline proinsulin / insulin ration [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline lipid and lipoprotein values: TC, LDL, HDL, TG, VLDL, apoB-100 [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Change and % change from baseline fasting proinsulin [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse Events [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
Clinical laboratory tests [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
12 lead ECG [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
vital signs assessments, weight change, physical exams [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]
concomitant medications [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	72
Study Start Date:	February 2007
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Placebo Comparator Sulfonylurea + 100 mg/week ISIS 113715 or placebo	Drug: ISIS 113715 doses of 100 and 200 mg per week
B: Placebo Comparator Sulfonylurea + 200 mg/week ISIS 113715 or placebo	Drug: ISIS 113715 doses of 100 and 200 mg per week

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455598

Locations

Poland
Akademickie Centrum Kliniczne- Szpital Akademii Medycznej w Gdańsku
Gdańsk, Poland, 80-952
Poradnia Neurologiczna i Poradnia
Poznań, Poland, 61-289
Indywidualna Specjalistyczna Praktyka Lekarska
Szczecin, Poland, 70-361
ll Oddzial Chorob Wewnetrznych
Tychy, Poland, 43-100
Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno
Bialystok, Poland, 15-435
Niepubliczny Zakład Opieki
Radom, Poland, 26-610
Samodzielny Zespół Publicznych Zakladów Opieki Zdrowotnej
Wolomin, Poland, 05-200
Romania
Cardiology Private PRactice "Dr. Calin Pop"
Baia Mare, Romania, 430123
Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases
Satu Mare, Romania, 440055
"Sf. Ioan cel Nou" Suceava Emergencency County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
Suceava, Romania, 720284
Deva County Hospital, Department of Internal Medicine
Deva, Romania, 330084
Medical Centre of Diagnosis, Outpatient Treatment and Preventive Medicine, Department of Diabetes, Nutrition and Metabolic Diseases
Bucharest, Romania, 011794
Arad Emergency Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
Arad, Romania, 310158
"Nicolae Malaxa" Clinical Hospital, Department of Diabetes, Nutrition and Metabolic Diseases
Bucharest, Romania, 022441
"Prof. Dr. N.C. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, 1st Clinical Department of Diabetes, Nutrition and Metabolic Diseases
Bucharest, Romania, 020475
Private Practice Nicodiab SRL
Bucharest, Romania, 010507
Private Practice "Morosanu V. Magdalena"
Galati, Romania, 800371
Sibiu Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
Sibiu, Romania, 550245
Oradea Clinical County Hospital, Department of Diabetes, Nutrition and Metabolic Diseases
Oradea, Romania, 410032
Private Practice "Dr. Gagiu Remus"
Targoviste, Romania, 130083
S.C. Diabmed Dr. Popescu Alexandrina SRL
Ploiesti, Romania, 100163
Cluj Emergency Clinical County Hospital
Cluj-Napoca, Romania, 400006
Private Practice SC "Diabol" SRL
Brasov, Romania, 500365
Russian Federation
Limited Liability Company "Clinic of New Medical Technologies"
Moscow, Russian Federation, 140091
State Institution "Moscow Regional Scientific Research Clinical Institute named after M.F. Vladimirsky
Moscow, Russian Federation, 129110
State Institution "Endocrinology Scientific Center of the RAMS",
Moscow, Russian Federation, 115478
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, Russian Federation, 125315
Medical Institution Public Corporation Polyclinic "Gazprom"
Moscow, Russian Federation, 117420
Close Corporation "MEDSI"
Moscow, Russian Federation, 123056
State Educational Institution of High Professional Education <Siberian State University of Federal Agency of Healthcare and Social Development
Tomsk, Russian Federation, 634034
Municipal Institution of Healthcare Clinical Ambulance Hospital named after N. V. Soloviev
Yaroslavl, Russian Federation, 150003
State Educational Institution of High Professional Education "Smolensk State Medical Academy of Federal Agency of Healthcare and Social Development
Smolensk, Russian Federation, 214018
Public Medical Institution "City Outpatient Clinic # 20" of Saratov Administration Healthcare
Saratov, Russian Federation, 410018
Limited Liability Company "Center "Diabetes"
Samara, Russian Federation, 443067
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, Russian Federation, 194156
State Institution of Healthcare "Kemerovo Regional Clinical Hospital"
Kemerovo, Russian Federation, 650066
Regional State Institution of Healthcare "Novosibirsk State Regional Clinical Hospital"
Novosibirsk, Russian Federation, 630087
State Institution Scientific Research Institute of Therapy of the Siberian Department of the Russian Academy of Medical Sciences
Novosibirsk, Russian Federation, 630089
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
St. Petersburg, Russian Federation, 198013

Sponsors and Collaborators

Isis Pharmaceuticals

Investigators

Study Chair:

Isis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Isis Pharmaceuticals ( Isis Pharmaceuticals )
Study ID Numbers:	113715-CS14, EudraCT No: 2006-005718-11
Study First Received:	April 2, 2007
Last Updated:	February 8, 2009
ClinicalTrials.gov Identifier:	NCT00455598 History of Changes
Health Authority:	Poland: Ministry of Health; Poland: Ministry of Science and Higher Education; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Russia: Ethics Committee; Russia: Ministry of Health and Social Development of the Russian Federation; Russia: Pharmacological Committee, Ministry of Health

Keywords provided by Isis Pharmaceuticals:

Diabetes

Study placed in the following topic categories:

Metabolic Diseases
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases

Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder

Additional relevant MeSH terms:

Metabolic Diseases
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on March 13, 2009