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

This study has been completed.
Sponsor:
Information provided by:
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00455598
First received: April 2, 2007
Last updated: August 26, 2009
Last verified: August 2009

April 2, 2007
August 26, 2009
February 2007
March 2009   (final data collection date for primary outcome measure)
  • 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 fasting proinsulin [ 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 Adiponectin [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Enhance sensitivity to insulin without development of hypoglicemia.
Complete list of historical versions of study NCT00455598 on ClinicalTrials.gov Archive Site
  • 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 ]
Lower serum triglyceride levels and reduce body weight and fat mass.
Not Provided
Not Provided
 
Placebo Controlled, Dose Escalation Study in Subjects With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
Drug: ISIS 113715
doses of 100 and 200 mg per week
  • Placebo Comparator: A
    Sulfonylurea + 100 mg/week ISIS 113715 or placebo
    Intervention: Drug: ISIS 113715
  • Placebo Comparator: B
    Sulfonylurea + 200 mg/week ISIS 113715 or placebo
    Intervention: Drug: ISIS 113715
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
88
May 2009
March 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Romania,   Poland,   Russian Federation
 
NCT00455598
113715-CS14, EudraCT No: 2006-005718-11
No
Isis Pharmaceuticals
Isis Pharmaceuticals
Not Provided
Study Chair: Isis Pharmaceuticals Isis Pharmaceuticals
Isis Pharmaceuticals
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP