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

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ISIS 113715

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Diabetes

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno
Akademickie Centrum Kliniczne- Szpital Akademii Medycznej w Gdańsku
Poradnia Neurologiczna i Poradnia
Niepubliczny Zakład Opieki
Indywidualna Specjalistyczna Praktyka Lekarska
ll Oddzial Chorob Wewnetrznych
Samodzielny Zespół Publicznych Zakladów Opieki Zdrowotnej
Arad Emergency Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
Cardiology Private PRactice "Dr. Calin Pop"
Private Practice SC "Diabol" SRL
Private Practice Nicodiab SRL
Medical Centre of Diagnosis, Outpatient Treatment and Preventive Medicine, Department of Diabetes, Nutrition and Metabolic Diseases
"Prof. Dr. N.C. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, 1st Clinical Department of Diabetes, Nutrition and Metabolic Diseases
"Nicolae Malaxa" Clinical Hospital, Department of Diabetes, Nutrition and Metabolic Diseases
Cluj Emergency Clinical County Hospital
Deva County Hospital, Department of Internal Medicine
Private Practice "Morosanu V. Magdalena"
Oradea Clinical County Hospital, Department of Diabetes, Nutrition and Metabolic Diseases
S.C. Diabmed Dr. Popescu Alexandrina SRL
Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases
Sibiu Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
"Sf. Ioan cel Nou" Suceava Emergencency County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases
Private Practice "Dr. Gagiu Remus"
State Institution of Healthcare "Kemerovo Regional Clinical Hospital"
State Institution "Endocrinology Scientific Center of the RAMS",
Medical Institution Public Corporation Polyclinic "Gazprom"
Close Corporation "MEDSI"
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
State Institution "Moscow Regional Scientific Research Clinical Institute named after M.F. Vladimirsky
Limited Liability Company "Clinic of New Medical Technologies"
Regional State Institution of Healthcare "Novosibirsk State Regional Clinical Hospital"
State Institution Scientific Research Institute of Therapy of the Siberian Department of the Russian Academy of Medical Sciences
Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Federal Agency on High Technology Medical Care
Limited Liability Company "Center "Diabetes"
Public Medical Institution "City Outpatient Clinic # 20" of Saratov Administration Healthcare
State Educational Institution of High Professional Education "Smolensk State Medical Academy of Federal Agency of Healthcare and Social Development
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
State Educational Institution of High Professional Education <Siberian State University of Federal Agency of Healthcare and Social Development
Municipal Institution of Healthcare Clinical Ambulance Hospital named after N. V. Soloviev

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Arm Label

Arm Description

Sulfonylurea + 100 mg/week ISIS 113715 or placebo

Sulfonylurea + 200 mg/week ISIS 113715 or placebo

Outcomes

Primary Outcome Measures

Change and % change from baseline HbA1c

Change and % change from baseline fasting glucose (serum and plasma)

Change and % change from baseline seven point glucose profile

Change and % change from baseline mean fasting and insulin c-peptide

Change and % change from baseline fasting proinsulin

Change and % change from baseline proinsulin / insulin ration

Change and % change from baseline lipid and lipoprotein values: TC, LDL, HDL, TG, VLDL, apoB-100

Change and % change from baseline Adiponectin

Secondary Outcome Measures

Adverse Events

Clinical laboratory tests

12 lead ECG

vital signs assessments, weight change, physical exams

concomitant medications

Full Information

NCT ID

NCT00455598

First Posted

April 2, 2007

Last Updated

August 26, 2009

Sponsor

Ionis Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00455598

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2009

Overall Recruitment Status

Completed

Study Start Date

February 2007 (undefined)

Primary Completion Date

March 2009 (Actual)

Study Completion Date

May 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Ionis Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

88 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Placebo Comparator

Arm Description

Sulfonylurea + 100 mg/week ISIS 113715 or placebo

Arm Title

Arm Type

Placebo Comparator

Arm Description

Sulfonylurea + 200 mg/week ISIS 113715 or placebo

Intervention Type

Drug

Intervention Name(s)

ISIS 113715

Intervention Description

doses of 100 and 200 mg per week

Primary Outcome Measure Information:

Title

Change and % change from baseline HbA1c

Time Frame

13 weeks

Title

Change and % change from baseline fasting glucose (serum and plasma)

Time Frame

13 weeks

Title

Change and % change from baseline seven point glucose profile

Time Frame

13 weeks

Title

Change and % change from baseline mean fasting and insulin c-peptide

Time Frame

13 weeks

Title

Change and % change from baseline fasting proinsulin

Time Frame

13 weeks

Title

Change and % change from baseline proinsulin / insulin ration

Time Frame

13 weeks

Title

Change and % change from baseline lipid and lipoprotein values: TC, LDL, HDL, TG, VLDL, apoB-100

Time Frame

13 weeks

Title

Change and % change from baseline Adiponectin

Time Frame

13 weeks

Secondary Outcome Measure Information:

Title

Adverse Events

Time Frame

13 weeks

Title

Clinical laboratory tests

Time Frame

13 weeks

Title

12 lead ECG

Time Frame

13 weeks

Title

vital signs assessments, weight change, physical exams

Time Frame

13 weeks

Title

concomitant medications

Time Frame

13 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Isis Pharmaceuticals

Organizational Affiliation

Ionis Pharmaceuticals, Inc.

Official's Role

Study Chair

Facility Information:

Facility Name

Niepubliczny Zakład Opieki Zdrowotnej Specjalistyczny Ośrodek Internistyczno

City

Bialystok

ZIP/Postal Code

15-435

Country

Poland

Facility Name

Akademickie Centrum Kliniczne- Szpital Akademii Medycznej w Gdańsku

City

Gdańsk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Poradnia Neurologiczna i Poradnia

City

Poznań

ZIP/Postal Code

61-289

Country

Poland

Facility Name

Niepubliczny Zakład Opieki

City

Radom

ZIP/Postal Code

26-610

Country

Poland

Facility Name

Indywidualna Specjalistyczna Praktyka Lekarska

City

Szczecin

ZIP/Postal Code

70-361

Country

Poland

Facility Name

ll Oddzial Chorob Wewnetrznych

City

Tychy

ZIP/Postal Code

43-100

Country

Poland

Facility Name

Samodzielny Zespół Publicznych Zakladów Opieki Zdrowotnej

City

Wolomin

ZIP/Postal Code

05-200

Country

Poland

Facility Name

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

City

Arad

ZIP/Postal Code

310158

Country

Romania

Facility Name

Cardiology Private PRactice "Dr. Calin Pop"

City

Baia Mare

ZIP/Postal Code

430123

Country

Romania

Facility Name

Private Practice SC "Diabol" SRL

City

Brasov

ZIP/Postal Code

500365

Country

Romania

Facility Name

Private Practice Nicodiab SRL

City

Bucharest

ZIP/Postal Code

010507

Country

Romania

Facility Name

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

City

Bucharest

ZIP/Postal Code

011794

Country

Romania

Facility Name

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

City

Bucharest

ZIP/Postal Code

020475

Country

Romania

Facility Name

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

City

Bucharest

ZIP/Postal Code

022441

Country

Romania

Facility Name

Cluj Emergency Clinical County Hospital

City

Cluj-Napoca

ZIP/Postal Code

400006

Country

Romania

Facility Name

Deva County Hospital, Department of Internal Medicine

City

Deva

ZIP/Postal Code

330084

Country

Romania

Facility Name

Private Practice "Morosanu V. Magdalena"

City

Galati

ZIP/Postal Code

800371

Country

Romania

Facility Name

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

City

Oradea

ZIP/Postal Code

410032

Country

Romania

Facility Name

S.C. Diabmed Dr. Popescu Alexandrina SRL

City

Ploiesti

ZIP/Postal Code

100163

Country

Romania

Facility Name

Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases

City

Satu Mare

ZIP/Postal Code

440055

Country

Romania

Facility Name

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

City

Sibiu

ZIP/Postal Code

550245

Country

Romania

Facility Name

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

City

Suceava

ZIP/Postal Code

720284

Country

Romania

Facility Name

Private Practice "Dr. Gagiu Remus"

City

Targoviste

ZIP/Postal Code

130083

Country

Romania

Facility Name

State Institution of Healthcare "Kemerovo Regional Clinical Hospital"

City

Kemerovo

ZIP/Postal Code

650066

Country

Russian Federation

Facility Name

State Institution "Endocrinology Scientific Center of the RAMS",

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Facility Name

Medical Institution Public Corporation Polyclinic "Gazprom"

City

Moscow

ZIP/Postal Code

117420

Country

Russian Federation

Facility Name

Close Corporation "MEDSI"

City

Moscow

ZIP/Postal Code

123056

Country

Russian Federation

Facility Name

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

City

Moscow

ZIP/Postal Code

125315

Country

Russian Federation

Facility Name

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

City

Moscow

ZIP/Postal Code

129110

Country

Russian Federation

Facility Name

Limited Liability Company "Clinic of New Medical Technologies"

City

Moscow

ZIP/Postal Code

140091

Country

Russian Federation

Facility Name

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

City

Novosibirsk

ZIP/Postal Code

630087

Country

Russian Federation

Facility Name

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

City

Novosibirsk

ZIP/Postal Code

630089

Country

Russian Federation

Facility Name

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

City

Saint-Petersburg

ZIP/Postal Code

194156

Country

Russian Federation

Facility Name

Limited Liability Company "Center "Diabetes"

City

Samara

ZIP/Postal Code

443067

Country

Russian Federation

Facility Name

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

City

Saratov

ZIP/Postal Code

410018

Country

Russian Federation

Facility Name

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

City

Smolensk

ZIP/Postal Code

214018

Country

Russian Federation

Facility Name

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

City

St. Petersburg

ZIP/Postal Code

198013

Country

Russian Federation

Facility Name

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

City

Tomsk

ZIP/Postal Code

634034

Country

Russian Federation

Facility Name

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

City

Yaroslavl

ZIP/Postal Code

150003

Country

Russian Federation

12. IPD Sharing Statement

Learn more about this trial

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

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