Clinical trial NCT00327626: Safety, Tolerability, and Activity of ISIS 113715 in People 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, Pharmacokinetics, and Activity of ISIS 113715 Administered Daily in Patients With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: Fasting plasma glucose
HbA1c
Oral antidiabetic agent(s)
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2006-05-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the safety, tolerability, and pharmacokinetics of two ISIS 113715 subcutaneous doses (15 mg and 30 mg/day) in combination with oral antidiabetic agents (OAD) versus OAD + placebo in patients with inadequately controlled type 2 diabetes, despite ongoing maximal treatment with OAD.


Eligibility criteria: Inclusion Criteria:

* Male or female (post-menopausal and/or surgically sterile)
* Aged 18 to 70 years
* Diagnosed with type 2 diabetes mellitus of eight years or less in duration
* Being treated with OAD at stable maximum doses \[defined as at least 10 mg/day glibenclamide (preferred), or 20 mg/day glipizide, with or without at least 1,500 mg/day metformin\] for at least three months prior to screening
* Having fasting plasma glucose levels of 150-270 mg/dL and HbA1c levels of 7.5-11.0%

Exclusion Criteria:

* Greater than 3 severe hypoglycemic episodes within six months of screen
* Pregnant, breastfeeding, or intends to become pregnant
* Clinical signs or symptoms of liver disease, acute, or chronic hepatitis, or ALT greater than the upper limit of normal
* Positive hepatitis B surface antigen, hepatitis C antibody, or HIV test
* Patients with history of renal transplantation or renal dialysis or microalbuminuria defined as urine albumin \> 200 mg/day
* History of insulin use within three months of screen
* History of diabetic ketoacidosis
* Treatment with any thiazolidinedione (e.g., rosiglitazone) within three months of screen
* History of lactic acidosis while on metformin therapy
* Complications of diabetes (e.g., neuropathy, nephropathy, and retinopathy)
* Clinically significant and currently active diseases
* Clinical significant abnormalities in medical history, physical examination, or laboratory examination

Primary outcomes:
measure: Evaluate the safety, tolerability, and pharmacokinetics of two ISIS 113715 subcutaneous dosages in combination with OAD versus OAD + placebo.
measure: Examine the effect of treatment with 15 and 30 mg/day ISIS 113715 on fasting plasma glucose and HbA1c.
measure: Evaluate the effects of ISIS 113715 on insulin sensitivity, B-cell function, proinsulin/insulin ratio, fasting insulin, C-peptide and proinsulin.
Secondary outcomes:
Other outcomes:
Locations:
city: BeEr-Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Medical Center - Nahariya
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Safed
country: Israel
facility: ZIV Hospital
Study officials:
affiliation: Ionis Pharmaceuticals, Inc.
name: Mark K Wedel, MD, JD, FACP
role: STUDY_DIRECTOR
References: