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

NCT00455598 | Completed Phase 2

• 2 other identifiers: 113715-CS14EudraCT No: 2006-005718-11
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 39

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (5)

• 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

Study Arms (2)

A

PLACEBO COMPARATOR

Sulfonylurea + 100 mg/week ISIS 113715 or placebo

Drug: ISIS 113715

B

PLACEBO COMPARATOR

Sulfonylurea + 200 mg/week ISIS 113715 or placebo

Drug: ISIS 113715

Interventions

ISIS 113715 DRUG

doses of 100 and 200 mg per week

A; B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (39)

Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno

Bialystok, 15-435, Poland

Location

Akademickie Centrum Kliniczne- Szpital Akademii Medycznej w Gdańsku

Gdansk, 80-952, Poland

Location

Poradnia Neurologiczna i Poradnia

Poznan, 61-289, Poland

Location

Niepubliczny Zakład Opieki

Radom, 26-610, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska

Szczecin, 70-361, Poland

Location

ll Oddzial Chorob Wewnetrznych

Tychy, 43-100, Poland

Location

Samodzielny Zespół Publicznych Zakladów Opieki Zdrowotnej

Wołomin, 05-200, Poland

Location

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

Arad, 310158, Romania

Location

Cardiology Private PRactice "Dr. Calin Pop"

Baia Mare, 430123, Romania

Location

Private Practice SC "Diabol" SRL

Brasov, 500365, Romania

Location

Private Practice Nicodiab SRL

Bucharest, 010507, Romania

Location

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

Bucharest, 011794, Romania

Location

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

Bucharest, 020475, Romania

Location

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

Bucharest, 022441, Romania

Location

Cluj Emergency Clinical County Hospital

Cluj-Napoca, 400006, Romania

Location

Deva County Hospital, Department of Internal Medicine

Deva, 330084, Romania

Location

Private Practice "Morosanu V. Magdalena"

Galati, 800371, Romania

Location

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

Oradea, 410032, Romania

Location

S.C. Diabmed Dr. Popescu Alexandrina SRL

Ploieşti, 100163, Romania

Location

Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases

Satu Mare, 440055, Romania

Location

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

Sibiu, 550245, Romania

Location

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

Suceava, 720284, Romania

Location

Private Practice "Dr. Gagiu Remus"

Târgovişte, 130083, Romania

Location

State Institution of Healthcare "Kemerovo Regional Clinical Hospital"

Kemerovo, 650066, Russia

Location

State Institution "Endocrinology Scientific Center of the RAMS",

Moscow, 115478, Russia

Location

Medical Institution Public Corporation Polyclinic "Gazprom"

Moscow, 117420, Russia

Location

Close Corporation "MEDSI"

Moscow, 123056, Russia

Location

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, 125315, Russia

Location

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

Moscow, 129110, Russia

Location

Limited Liability Company "Clinic of New Medical Technologies"

Moscow, 140091, Russia

Location

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

Novosibirsk, 630087, Russia

Location

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

Novosibirsk, 630089, Russia

Location

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, 194156, Russia

Location

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, 198013, Russia

Location

Limited Liability Company "Center "Diabetes"

Samara, 443067, Russia

Location

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

Saratov, 410018, Russia

Location

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

Smolensk, 214018, Russia

Location

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

Tomsk, 634034, Russia

Location

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

Yaroslavl, 150003, Russia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

ISIS-113715

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Isis Pharmaceuticals

  Ionis Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 2, 2007
• First Posted: April 3, 2007
• Study Start: February 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: May 1, 2009
• Last Updated: August 28, 2009

Record last verified: 2009-08

Locations

RO (16); RU (16); PL (7)