Clinical trial NCT01918865: Safety, Tolerability, and Efficacy of ISIS-PTP1BRx in Type 2 Diabetes
Official title: A Double Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of ISIS 404173 Administered Once Weekly to Obese Patients With Type 2 Diabetes Mellitus Being Treated With Metformin or Metformin Plus Sulfonylurea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Obese
Keywords: Type 2 Diabetes Mellitus
T2DM
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-08
Enrollment: 92
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 purpose of this study is to evaluate the safety, tolerability, and efficacy of ISIS-PTP1BRx + oral antidiabetic drug/s (metformin and/or sulfonylurea) versus placebo + oral antidiabetic drug/s.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) \>/= 27 kg/m2
* HbA1c between 7.5% and 10.5% (inclusive)
* C-Peptide (fasting) greater than or equal to 500 pmol/L
* On stable dose of metformin alone or in combination with a stable dose of sulfonylurea for \>/= 3 months prior to screening, and remain on stable dose throughout the study
* Agree to conduct home-based (fasted) blood glucose testing as directed

Exclusion Criteria:

* Clinically significant abnormalities in medical history or physical exam
* Serum creatinine \> ULN at Screening
* Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT or AST \> 1.5x ULN at Screening
* History of renal transplantation or renal dialysis
* GFR \< 60 mL/min at Screening
* History of diabetic ketoacidosis
* History of greater than 3 episodes of severe hypoglycemia within 6 months of screening
* Allergy to sulfur containing drugs
* Treatment with other drugs or medications not allowed per study specific Disallowed Concomitant Medicines
* 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: Incidence, severity, dose-relationship of adverse effects, and changes in laboratory evaluations as a measure of safety
timeFrame: 38 weeks
measure: Change in plasma HbA1c levels at Week 27 compared to Baseline as a measure of efficacy
timeFrame: 27 weeks
Secondary outcomes:
measure: Change in FPG, weekly average SMPG, seven-point glucose profile, lipid profile, body weight, & BMI at Week 27 compared to Baseline as a measure of efficacy
timeFrame: 27 Weeks
Other outcomes:
Locations:
city: Mar del Plata
country: Argentina
facility: Isis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Isis Investigative Site
state: Santa Fe
city: Edmonton
country: Canada
facility: Isis Investigational Site
state: Alberta
city: Kelowna
country: Canada
facility: Isis Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Isis Investigational Site
state: British Columbia
city: Etobicoke
country: Canada
facility: Isis Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Isis Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Isis Investigative Site
state: Ontario
city: Saskatoon
country: Canada
facility: Isis Investigational Site
state: Saskatchewan
city: Centurion
country: South Africa
facility: Isis Investigational Site
state: Gauteng
city: Mamelodi
country: South Africa
facility: Isis Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Isis Investigational Site
state: Gauteng
city: Port Elizabeth
country: South Africa
facility: Isis Investigational Site
state: Korsten
city: Durban
country: South Africa
facility: Isis Investigational Site
state: KwaZulu-Natal
city: Middelburg
country: South Africa
facility: Isis Investigational Site
state: Mpumalanga
city: Limpopo
country: South Africa
facility: Isis Investigational Site
state: Thabazimbi
city: Cape Town
country: South Africa
facility: Isis Investigational Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Isis Investigational Site
state: Western Cape
city: Benoni
country: South Africa
facility: Isis Investigational Site
city: Bloemfontein
country: South Africa
facility: Isis Investigational Site
city: Pretoria
country: South Africa
facility: Isis Investigational Site
Study officials:
References:
citation: Digenio A, Pham NC, Watts LM, Morgan ES, Jung SW, Baker BF, Geary RS, Bhanot S. Antisense Inhibition of Protein Tyrosine Phosphatase 1B With IONIS-PTP-1BRx Improves Insulin Sensitivity and Reduces Weight in Overweight Patients With Type 2 Diabetes. Diabetes Care. 2018 Apr;41(4):807-814. doi: 10.2337/dc17-2132. Epub 2018 Feb 9.