Hyperglycemia in patients with type 2 diabetes MedDRA version: 18.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 18.1 Level: LLT Classification code 10020639 Term: Hyperglycemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Code: ISIS 449884
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ISIS 449884
CAS Number: 1428588-67-3
Current Sponsor code: ISIS 449884
Other descriptive name: ISIS 449884
Co
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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, inclusive, at the time of informed consent 3. Satisfy the following: • Females: Non-pregnant and non-lactating; surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females = 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved), or if engaged in sexual relations and of child-bearing potential, subject is using an acceptable contraceptive method from the time of signing the informed consent form until at least 18 weeks after the last dose of Study Drug. • Males: Surgically sterile, abstinent or if engaged in sexual relations with a female of child-bearing potential, subject is utilizing an acceptable contraceptive method from the time of signing the informed consent form until at least 18 weeks after the last dose of Study Drug. 4. Body Mass Index (BMI) = 25.0 - =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1.Clinically significant abnormalities in medical history or physical examination 2.Screening laboratory results as follows or any other clinically significant abnormalities in screening laboratory values that would render a patient unsuitable for inclusion a.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 ULN d.Estimated GFR ULN, bilirubin > ULN at Screening f.Have a current or previous diagnosis of Gilbert’s disease g.Platelet count 40 mg/dL (> 2.2 mmol/L) at the Pre-treatment Visit (Week -2, Day -14) compared to a FPG value taken during the Screening Period; or fasted self-monitored plasma glucose (SMPG) values 75% of measurements collected during Screening through Wk -3 (up to Day -14 visit) 9.Patients receiving treatment with statins must have been on a stable dose and regimen for = 3 months prior to Screening and should be within the dose levels listed below. Other statin regimens should be discussed and approved with the Sponsor Medical Monitor or designee. •Simvastatin at = 40 mg/day •Lovastatin at = 20 mg/day •Atorvastatin and fluvastatin up to 40 mg/day •Rosuvastatin up to 20 mg/day or pravastatin up to 40 mg/day •Pitavastatin up to 4 mg/day 10.Treatment with non-selective beta-blockers such as propranolol within 3 months of screening and throughout the study 11.Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1 12.Malignancy within 5 years of signing informed consent, with some exceptions 13.Treatment with another investigational drug, biological agent, or device within one (1) month of screening, or 5 half-lives of investigational drug, whichever is longer 14.Treatment with any non-ISIS oligonucleotide (including siRNA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the pharmacodynamics effects of GCGR Reduction by ISIS 449884 (100 mg) on Hepatic Lipid and Glycogen Content.;Secondary Objective: To evaluate the safety, tolerability and pharmacokinetic profile of ISIS 449884.;Primary end point(s): PHARMACODYNAMIC • Differences in percent hepatic glycogen content between Baseline and post-treatment assessments for ISIS 449884 100 mg and placebo patients • Differences in percent hepatic lipid content between Baseline and post-treatment assessments for ISIS 449884 100 mg and placebo patients • Change from Baseline in percent fasting hepatic glycogen content and percent fasting hepatic lipid content for each patient who has MRS procedures conducted at Baseline, Week 6 and Week 14. • Change and percent change from Baseline to Week 14 in fasting plasma glucagon and fasting plasma total GLP-1 between ISIS 449884 100 mg and placebo group EFFICACY Comparisons of change and percent change from Baseline to Week 14 in HbA1c, FPG, plasma insulin, plasma C-peptide and weekly average SMPG between ISIS 449884 100 mg and placebo group in the Per-Protocol Set and Full Analysis Set. SAFETY The safety endpoints include: • Adverse events • Vital signs (including blood pressure) and body weight • Physical examination • Clinical laboratory tests (serum chemistry, hematology, urinalysis, coagulation, lipids, antibodies, pregnancy test for women with childbearing potential) • ECG • Use of concomitant medication;Timepoint(s) of evaluation of this end point: Evaluation will take place at the end of the study. PHARMACODYNAMIC • Between baseline and post-treatment assessments • Between baseline and post-treatment assessments • Between baseline and Week 14 EFFICACY • Between baseline and Week 6 and Week 14 SAFETY • Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): No additional end points;Timepoint(s) of evaluation of this end point: Not Applicable | — |
Countries
Austria, Hungary, Slovakia
Contacts
Public ContactTeresa Brandt
Ionis Pharmaceuticals, Inc.
Outcome results
None listed