Clinical trial NCT02824003: Study to Evaluate the Effect of ISIS GCGRRx on Hepatic Lipid and Glycogen Content in Type 2 Diabetes
Official title: Double Blind, Randomized, Placebo-Controlled, Phase 2A Mechanistic Study to Evaluate the Effect of ISIS 449884 (ISIS-GCGRRx) on Hepatic Lipid and Glycogen Content in Patients With Type 2 Diabetes Being Treated With Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effect of ISIS 449884 (ISIS-GCGRRX) on Hepatic Lipid and Glycogen Content in patients with Type 2 Diabetes being treated with Metformin.


Eligibility criteria: Inclusion Criteria:

* Male or female, age 18 to 75
* BMI ≥ 25.0 kg/m2 \< 36.0 kg/m2
* HbA1c ≥ 7.5% and ≤ 10.5%
* Type 2 Diabetes Mellitus and on stable dose of Metformin. 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 evaluation and will be required to continue their stable dose of metformin throughout the study. Patients on a stable dose of metformin plus a sulfonylurea (SU) or metformin plus a dipeptidyl peptidase-IV (DPPIV) inhibitor for a minimum of 3 months prior to Screening evaluation may be allowed
* Agree to conduct home-based (fasted) blood glucose testing as directed

Exclusion Criteria:

* Clinically significant abnormalities in medical history or physical exam
* Show evidence of uncorrected hypothyroidism or hyperthyroidism
* History of liver transplantation or renal dialysis
* History of liver disease
* History of greater than 3 episodes of severe hypoglycemia within 6 months of screening
* Treatment with any other antidiabetic drug(s) other than metformin, SU or DPPIV within 3 months of screening
* History of diabetic ketoacidosis
* Any other significant illness or condition that may interfere with the patient participating or completing the study
* Inability or unwillingness to comply with protocol or study procedures -

Primary outcomes:
measure: Change in fasting hepatic glycogen content
timeFrame: Week 14
measure: Change in fasting hepatic lipid content
timeFrame: Week 14
Secondary outcomes:
measure: Safety and Tolerability will be assessed by determining the incidence, severity, dose relationship of adverse effects, and changes in laboratory evaluations
timeFrame: 38 weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Ionis Investigator Site
Study officials:
affiliation: Ionis Pharmaceuticals
name: Sanjay Bhanot
role: STUDY_DIRECTOR
References:
citation: Morgan ES, Tai LJ, Pham NC, Overman JK, Watts LM, Smith A, Jung SW, Gajdosik M, Krssak M, Krebs M, Geary RS, Baker BF, Bhanot S. Antisense Inhibition of Glucagon Receptor by IONIS-GCGRRx Improves Type 2 Diabetes Without Increase in Hepatic Glycogen Content in Patients With Type 2 Diabetes on Stable Metformin Therapy. Diabetes Care. 2019 Apr;42(4):585-593. doi: 10.2337/dc18-1343. Epub 2019 Feb 14.