Clinical trial NCT02227875: Non-inferiority Study to Compare the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 2 Diabetes Mellitus Patients (INSTRIDE 2)
Official title: An Open-label, Randomized, Multi-center, Parallel Group Clinical Trial Comparing the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 2 Diabetes Mellitus Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mylan GmbH
First posted: 2014-08-28
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To test whether Mylan's insulin glargine once daily is non-inferior to Lantus® once daily (both administered in combination with other anti-diabetic drugs) based on the change in HbA1c from baseline to 24 weeks

Detailed description: This trial is a multi-center, open-label, randomized, parallel group trial in patients with T2DM comparing the efficacy and safety of Mylan's insulin glargine with that of Lantus®. Patients with an established diagnosis of T2DM per ADA 2014 criteria and who satisfy the selection criteria will be included in the trial. This will be followed by a 24-week randomized, comparative, parallel-assignment treatment period with Mylan's insulin glargine or Lantus® (in addition to other anti-diabetic drugs). After the treatment period, there will be a follow-up visit; 4 weeks after the patient has been put back on approved medications.

Eligibility criteria: Inclusion Criteria:

* Patients with an established diagnosis of T2DM per ADA 2014 criteria who also fulfill the following:

  * Diagnosis established 1 year prior to screening
  * Insulin-naïve OR
  * On Lantus® once daily at stable dose (±15% variation in dose) for at least 3 months prior to screening
* Body mass index (BMI) of 18.50 to 40.00 kg/m2 at screening (both values inclusive).
* Stable weight, with no more than 5 kg gain or loss, in the 3 months prior to screening; this information will be collected by patient interview during medical history.
* Hemoglobin ≥9.0 g/dL at screening
* Glycosylated hemoglobin (HbA1c) of \<10.5% or between 7.5 to 10.5% for insulin naïve patients at screening.

Exclusion Criteria:

* History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analog preparations used in the trial, OR history of significant allergic drug reactions.
* History of use of animal insulin within the last 3 years, any insulin other than Lantus® within the last 3 months prior to screening, or use of biosimilar insulin glargine at any time prior to screening.
* Patients requiring basal-bolus insulin therapy or who in the opinion of the investigator require mealtime insulin in order to achieve glycemic control.
* Regular use of immune-modulator therapy in the 1 year prior to screening.
* History of ≥2 episodes of severe hypoglycemia within the 6 months before screening or history of hypoglycemia unawareness (a sample questionnaire is provided in Appendix I) as judged by the investigator.
* History of ≥1 episode of hyperglycemic hyperosmolar coma or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening.
* Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg) or hepatitis C (HCVAb) antibodies at screening.
* History of drug or alcohol dependence or abuse during the 1 year prior to screening.
* Receipt of another investigational drug in the 3 months prior to screening (or as per local regulations), or if the screening visit is within 5 half-lives of another investigational drug (whichever is longer), or scheduled to receive another investigational drug during the current trial period.

Primary outcomes:
measure: Change in HbA1c From Baseline to 24 Weeks
timeFrame: 24 weeks
Secondary outcomes:
measure: Rate of Hypoglycemic Events Per 30 Days
timeFrame: Baseline and up to 24 weeks
measure: Hypoglycemia Occurrence
timeFrame: 24 weeks
measure: Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time
timeFrame: Week 12 and week 24
measure: Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time
timeFrame: week 12 and week 24
measure: Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time
timeFrame: week 12 and week 24
measure: Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time
timeFrame: Week 12 and week 24
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Mylan Investigational Site
state: Arizona
city: Bell Gardens
country: United States
facility: Mylan Investigational Site
state: California
city: Fresno
country: United States
facility: Mylan Investigational Site
state: California
city: Greenbrae
country: United States
facility: Mylan Investigational Site
state: California
city: Long Beach
country: United States
facility: Mylan Investigational Site
state: California
city: Los Angeles
country: United States
facility: Mylan Investigational Site
state: California
city: Los Gatos
country: United States
facility: Mylan Investigational Site
state: California
city: Mission Hills
country: United States
facility: Mylan Investigational Site
state: California
city: National City
country: United States
facility: Mylan Investigational Site
state: California
city: Northridge
country: United States
facility: Mylan Investigational Site
state: California
city: Orange
country: United States
facility: Mylan Investigational Site
state: California
city: Palm Springs
country: United States
facility: Mylan Investigational Site
state: California
city: Spring Valley
country: United States
facility: Mylan Investigational Site
state: California
city: Tustin
country: United States
facility: Mylan Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Mylan Investigational Site
state: California
city: West Hills
country: United States
facility: Mylan Investigational Site
state: California
city: Bradenton
country: United States
facility: Mylan Investigational Site
state: Florida
city: Cooper City
country: United States
facility: Mylan Investigational Site
state: Florida
city: Hialeah
country: United States
facility: Mylan Investigational Site
state: Florida
city: Miami
country: United States
facility: Mylan Investigational Site
state: Florida
city: Miami
country: United States
facility: Mylan Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Mylan Investigational Site
state: Florida
city: Palm Harbor
country: United States
facility: Mylan Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Mylan Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: Mylan Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: Mylan Investigational Site
state: Florida
city: Winter Haven
country: United States
facility: Mylan Investigational Site
state: Florida
city: Columbus
country: United States
facility: Mylan Investigational Site
state: Georgia
city: Gainesville
country: United States
facility: Mylan Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Mylan Investigational Site
state: Hawaii
city: Idaho Falls
country: United States
facility: Mylan Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Mylan Investigational Site
state: Illinois
city: Crystal Lake
country: United States
facility: Mylan Investigational Site
state: Illinois
city: Springfield
country: United States
facility: Mylan Investigational Site
state: Illinois
city: Anderson
country: United States
facility: Mylan Investigational Site
state: Indiana
city: Council Bluffs
country: United States
facility: Mylan Investigational Site
state: Iowa
city: Des Moines
country: United States
facility: Mylan Investigational Site
state: Iowa
city: Augusta
country: United States
facility: Mylan Investigational Site
state: Kansas
city: Topeka
country: United States
facility: Mylan Investigational Site
state: Kansas
city: Wichita
country: United States
facility: Mylan Investigational Site
state: Kansas
city: Crestview Hills
country: United States
facility: Mylan Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: Mylan Investigational Site
state: Kentucky
city: Waltham
country: United States
facility: Mylan Investigational Site
state: Massachusetts
city: Kansas City
country: United States
facility: Mylan Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Mylan Investigational Site
state: Missouri
city: Billings
country: United States
facility: Mylan Investigational Site
state: Montana
city: Lincoln
country: United States
facility: Mylan Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: Mylan Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: Mylan Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: Mylan Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: Mylan Investigational Site
state: Nevada
city: Nashua
country: United States
facility: Mylan Investigational Site
state: New Hampshire
city: Albany
country: United States
facility: Mylan Investigational Site
state: New York
city: Hartsdale
country: United States
facility: Mylan Investigational Site
state: New York
city: Smithtown
country: United States
facility: Mylan Investigational Site
state: New York
city: Staten Island
country: United States
facility: Mylan Investigational Site
state: New York
city: Asheville
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Burlington
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Cary
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Morehead City
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Mylan Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Mylan Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Mylan Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Mylan Investigational Site
state: Ohio
city: Bend
country: United States
facility: Mylan Investigational Site
state: Oregon
city: Charleston
country: United States
facility: Mylan Investigational Site
state: South Carolina
city: Greer
country: United States
facility: Mylan Investigational Site
state: South Carolina
city: Bristol
country: United States
facility: Mylan Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: Mylan Investigational Site
state: Tennessee
city: Memphis
country: United States
facility: Mylan Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Mylan Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: Mylan Investigational Site
state: Texas
city: Dallas
country: United States
facility: Mylan Investigational Site
state: Texas
city: Dallas
country: United States
facility: Mylan Investigational Site
state: Texas
city: El Paso
country: United States
facility: Mylan Investigational Site
state: Texas
city: Houston
country: United States
facility: Mylan Investigational Site
state: Texas
city: Houston
country: United States
facility: Mylan Investigational Site
state: Texas
city: McKinney
country: United States
facility: Mylan Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Mylan Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Mylan Investigational Site
state: Texas
city: Spring
country: United States
facility: Mylan Investigational Site
state: Texas
city: Victoria
country: United States
facility: Mylan Investigational Site
state: Texas
city: Ogden
country: United States
facility: Mylan Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Mylan Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Mylan Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Mylan Investigational Site
state: Utah
city: South Jordan
country: United States
facility: Mylan Investigational Site
state: Utah
city: Chesapeake
country: United States
facility: Mylan Investigational Site
state: Virginia
city: Manassas
country: United States
facility: Mylan Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: Mylan Investigational Site
state: Washington
city: Vancouver
country: United States
facility: Mylan Investigational Site
state: Washington
city: Amman
country: Jordan
facility: Mylan Investigational Site
city: Irbid
country: Jordan
facility: Mylan Investigational Site
city: Seoul
country: Korea, Republic of
facility: Mylan Investigational Site
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Mylan Investigational Site
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Mylan Investigational Site
city: Banska Bystrica
country: Slovakia
facility: Mylan Investigational Site
city: Bardejov
country: Slovakia
facility: Mylan Investigational Site
city: Bratislava
country: Slovakia
facility: Mylan Investigational Site
city: Dolny Kubin
country: Slovakia
facility: Mylan Investigational Site
city: Kosice
country: Slovakia
facility: Mylan Investigational Site
city: Levice
country: Slovakia
facility: Mylan Investigational Site
city: Sabinov
country: Slovakia
facility: Mylan Investigational Site
city: Sahy
country: Slovakia
facility: Mylan Investigational Site
city: Stropkov
country: Slovakia
facility: Mylan Investigational Site
city: Sturovo
country: Slovakia
facility: Mylan Investigational Site
city: Trebisov
country: Slovakia
facility: Mylan Investigational Site
city: Trencin
country: Slovakia
facility: Mylan Investigational Site
city: Zilina
country: Slovakia
facility: Mylan Investigational Site
city: Johannesburg
country: South Africa
facility: Mylan Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Mylan Investigational Site
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Mylan Investigational Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Mylan Investigational Site
state: Western Cape
city: Worcester
country: South Africa
facility: Mylan Investigational Site
state: Western Cape
city: Bloemfontein
country: South Africa
facility: Mylan Investigational Site
city: Kaohsiung
country: Taiwan
facility: Mylan Investigational Site
city: Taipei
country: Taiwan
facility: Mylan Investigational Site
Study officials:
affiliation: Texas Diabetes & Endocrinology
name: Thomas Blevins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sun B, Sengupta N, Rao A, Donnelly C, Waichale V, Roy AS, Ramaswamy S, Pathak D, Bowsher RR, Raiter Y, Aubonnet P, Barve A. Similar immunogenicity profiles between the proposed biosimilar MYL-1501D and reference insulin glargine in patients with diabetes mellitus: the phase 3 INSTRIDE 1 and INSTRIDE 2 studies. BMC Endocr Disord. 2021 Jun 26;21(1):129. doi: 10.1186/s12902-021-00797-4.