A controlled study to assess the safety, tolerability, and effectiveness of the study drug, ISIS 426115, in patients with Type 2 Diabetes who are being treated with Metformi
- Conditions
- Type 2 Diabetes MellitusMedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2013-002172-40-RO
- Lead Sponsor
- Isis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 40
1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
2. Males or females. Aged 18 to 75 years at the time of informed consent
3. Females must be non-pregnant and non-lactating and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal (12 months of natural [spontaneous] amenorrhea together with FSH confirmation of postmenopausal state). Males must be surgically sterile, abstinent or if engaged in sexual relations with women of child-bearing potential, the patient must be using an acceptable contraceptive method during dosing and for 12 weeks after the last dose of Study Drug
4. BMI =25 kg/m2
5. Clinically confirmed diagnosis of T2DM
6. Patients must have been on a stable dose of oral metformin (at least 1000 mg/day) for a minimum of 3 months prior to Screening and will be required to continue the stable dose of metformin throughout the study
7. HbA1c =7.5% and =10.5% at Screening
8. Agree to maintain current diet and exercise regimen throughout the study
9. Agree to conduct daily morning (fasted) blood glucose testing using the study glucometer throughout the study
10. Agree to abstain from alcoholic beverages 48 hours prior to Study Center visits
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Clinically significant abnormalities in medical history
2. Screening laboratory results as follows
• Urine protein/creatinine (P/C) ratio >0.2 mg/mg. In the event of P/C ratio above this threshold eligibility may be confirmed by a quantitative total urine protein measurement of <300 mg/24 hour
• Positive test (including trace) for blood on urinalysis. In the event of a positive test, eligibility may be confirmed with urine microscopy showing <5 red blood cells per high power field
• Serum creatinine >ULN
• Estimated GFR <60 mL/min (as determined by the Cockcroft-Gault Equation for Creatinine Clearance)
• History of or clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT or AST >1.5 x ULN; or total bilirubin >ULN at Screening
• Have a current or previous diagnosis of Gilbert’s disease
• Platelet count <140,000/mm3 at Screening
3. Show evidence of uncorrected hypothyroidism or hyperthyroidism at Screening. Patients receiving dose-stable thyroid replacement therapy for at least 3 months prior to Screening will be allowed to participate as long as thyroid tests (TSH/T3/T4) show that patient is euthyroid
4. History of renal transplantation or renal dialysis
5. Clinically significant complications of diabetes (e.g., history of painful neuropathy, nephropathy, proliferative retinopathy and/or foot ulcers)
6. Within 6 months prior to Screening have any of the following:
• More than 3 episodes of severe hypoglycemia requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions;
• One (1) event of hypoglycemia in which the patient required hospitalization;
• A current diagnosis of hypoglycemia unawareness
7. Treatment with antidiabetic drugs other than metformin including insulin, thiazolidinedione, a-glucosidase inhibitor, GLP-1 agonist or DPP-IV inhibitor and other drugs that may affect plasma glucose levels (including systemic glucocorticoids), systemic steroids, corticosteroids, antiglucocorticoid therapies including mifepristone and ketoconazole (topical cream and systemic), immunosuppressive medications, somatostatin analogues or ACTH therapy within 3 months prior to Screening
8. Confirmed reduction in fasting plasma glucose (FPG) of >40 mg/dL (>2.2 mmol/L) at the Pre-treatment Visit (Week-1, Day-7) compared to a FPG value taken during the Screening Period; or fasted self-monitored plasma glucose (SMPG) values <140 mg/dL for >75% of measurements collected during Week -3 through Week -2
9. History of diabetic ketoacidosis
10. Treatment with lipid lowering therapy with the exception of statins. Statins are allowed at stable doses (=3 months) prior to Screening and within the dose levels listed below. Other statin regimens should be discussed with the Sponsor Medical Monitor or designee
• Simvastatin at =40 mg/day
• Atorvastatin, fluvastatin, or lovastatin at =20 mg/day
• Rosuvastatin or pravastatin at =10 mg/day
• Pitavastatin at =2 mg/day
11. Treatment with non-selective beta-blockers such as propranolol within 3 months of Screening and
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: To evaluate the efficacy of ISIS 426115 subcutaneous injection (dosage: 210 mg/week) on the endpoint of serum fructosamine in combination with metformin versus metformin + placebo.<br> <br> To evaluate the safety and tolerability of ISIS 426115 subcutaneous injection (dosage: 210 mg/week) in combination with metformin versus metformin + placebo.<br> ;Secondary Objective: To evaluate the efficacy of ISIS 426115 subcutaneous injection on endpoints including fasting plasma glucose, insulin, C-peptide, serum glycated albumin, weekly average SMPG and serum lipids.;Primary end point(s): The primary efficacy endpoint is the change from Baseline to Week 7 in serum fructosamine concentration.;Timepoint(s) of evaluation of this end point: continuously
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): The secondary efficacy endpoints include:<br> •Percent change from Baseline to Week 7 in serum fructosamine<br> •Change and percent change from Baseline in HbA1c (if analyzed), fasting plasma glucose, weekly average SMPG, and glycated albumin<br> •Change and percent change from Baseline in fasting plasma glucose, fasting insulin and fasting C-peptide<br> •Change and percent change from Baseline in fasting total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, VLDL cholesterol, ApoA1, ApoB, ApoCIII, and Lp(a)<br> ;Timepoint(s) of evaluation of this end point: week 7