Mylan Insulin Glargine Study

• ClinicalTrials.gov Identifier: NCT03376789
• Recruitment Status: Completed
• First Posted: December 18, 2017
• Results First Posted: March 3, 2022
• Last Update Posted: March 3, 2022
• Sponsor: Mylan Inc.
• Collaborator: Mylan GmbH
• Information provided by (Responsible Party): Viatris Inc. ( Mylan Inc. )

Study Description

Brief Summary:

The aim of this study is to demonstrate similar efficacy and safety between MYL-1501D products produced from two manufacturing processes (Process V and Process VI) in combination with insulin lispro in patients with type 1 diabetes mellitus (T1DM).

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Drug: MYL-1501D product using manufacture process V; Drug: MYL-1501D product using manufacture process VI	Phase 3

Detailed Description:

This is a multicenter, double-blind, randomized, parallel-group Phase 3 study in subjects with type 1 diabetes mellitus (T1DM) comparing the efficacy, immunogenicity, and safety of MYL-1501D products from 2 manufacturing processes (Process V and Process VI). After a 2-week screening period, all subjects will be titrated on Lantus® during a 4-week run-in period and shifted from their current mealtime insulin to insulin lispro (Humalog®). Subjects will then be randomized (stratified by time of administration of glargine [morning and evening]) to 1 of 2 groups:

• MYL-1501D product from Process V
• MYL-1501D product from Process VI Treatment with MYL-1501D is for 18 weeks. A follow-up visit is scheduled 2 weeks after last dose of MYL 1501D.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multi-center, Double-Blind, Parallel-Group Clinical Study Comparing the Efficacy and Safety of MYL-1501D Produced by Two Manufacturing Processes in Type 1 Diabetes Mellitus Patients
• Actual Study Start Date: November 29, 2017
• Actual Primary Completion Date: September 25, 2018
• Actual Study Completion Date: January 10, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: MYL-1501D (Process V Product); MYL-1501D (Process V Product)	Drug: MYL-1501D product using manufacture process V; MYL-1501D product using manufacture process V
Active Comparator: MYL-1501D (Process VI Product); MYL-1501D (Process VI Product)	Drug: MYL-1501D product using manufacture process VI; MYL-1501D product using manufacture process VI

Outcome Measures

Primary Outcome Measures :

1. Change in HbA1c [ Time Frame: Baseline to Week 18 ]
   Change in HbA1c from baseline

Secondary Outcome Measures :

1. Change in FPG [ Time Frame: Baseline to Week 18 ]
   Change in fasting plasma glucose from baseline
2. Change in Insulin Dose [ Time Frame: Baseline to Week 18 ]
   Change in daily total insulin dose per unit body weight (U/kg) from baseline
3. Change in 8-point SMBG [ Time Frame: Baseline to Week 18 ]
   Change in 8-point self-monitored blood glucose (SMBG) daily average

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written and signed informed consent needs to be provided by subjects or their legal representatives before starting any protocol-specific procedures.
2. Male and female subjects between the ages of 18 to 65 years, both ages inclusive.

3. Subjects with an established diagnosis of T1DM per ADA 2017 criteria who also fulfil the following criteria:

   1. Initiation of insulin treatment within 6 months of T1DM diagnosis
   2. Treatment with basal-bolus insulin therapy for at least 1 year before screening
   3. Fasting plasma C-peptide <0.3 nmol/L at screening
   4. Subject has been on once daily Lantus® at stable dose (±15% variation in dose) for at least 3 months at screening
4. Body mass index (BMI) of 18.5 to 35 kg/m2 at screening (both values inclusive).
5. Stable weight, with no more than 5 kg gain or loss in the 3 months prior to screening, this information will be collected by subject interview during medical history.
6. Glycosylated hemoglobin (HbA1c) ≤ 9.5% at screening.
7. Hemoglobin ≥9.0 g/dL at screening.
8. Subject has the capability of communicating appropriately with the investigator.
9. Subject is able and willing to comply with the requirements of the study protocol including the 8-point self-monitored blood glucose (SMBG), completion of subject diary records and following a recommended diet and exercise plan for the entire duration of the study.

10. Female subjects of childbearing potential who are willing to use oral contraception or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through study completion.

    1. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    2. Postmenopausal females must have had no regular menstrual bleeding for at least 1 year prior to screening.
    3. Female subjects who report surgical sterilization must have had the procedure at least 6 months prior to screening.
    4. All female subjects of childbearing potential must have negative pregnancy test results at screening and at clinic visits, as per the SCHEDULE OF ACTIVITIES (SOA).
    5. If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than 6 months prior to screening

Exclusion Criteria:

1. History or presence of a medical condition or disease that in the investigator's opinion would place the subject at an unacceptable risk from study participation.
2. History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the study, OR history of significant allergic drug reactions.
3. History of use of animal insulin within the last 3 years or use of approved biosimilar insulin glargine at any time prior to study entry, except for subject who previously participated in MYL-1501D studies and were compliant with the study protocols.
4. History of use of a regular immunomodulator therapy in the 1 year prior to screening.
5. History of autoimmune disorders other than T1DM or insufficiently treated autoimmune thyroid disorders judged clinically relevant by the investigator (recorded while collecting subject history).
6. History of ≥1 episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening.
7. History of clinically significant acute bacterial, viral or fungal systemic infections in the last 4 weeks prior to screening (recorded while collecting subject history).
8. Any clinically significant abnormality in electrocardiogram (ECG) or safety laboratory tests (LFT, RFT, hematology or any other laboratory deemed clinically relevant by the investigator) conducted at screening and considered by the investigator to make the subject ineligible for the study.
9. Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HbSAg) or hepatitis C antibodies (HCVAb) at screening.
10. History of drug or alcohol dependence or abuse during the 1 year prior to screening.
11. 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 received (whichever is longer), or scheduled to receive another investigational drug during the current study period.

12. Subjects with the following secondary complications of diabetes:

    1. Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy examination / retinal photography (performed by a person legally authorized to do so) within the 6 months prior to screening.
    2. Clinical nephrotic syndrome or diabetic nephropathy with a serum creatinine level >1.5 times of upper limit of reference range at screening
    3. History of severe form of neuropathy or cardiac autonomic neuropathy, recorded while collecting subject history. Subject's with mild or moderate forms of neuropathy will be allowed.
    4. Subjects with a history of limb amputation as a complication of diabetes (at any time), or any vascular procedure during the 1 year prior to screening.
    5. History of diabetic foot or diabetic ulcers in the 1 year prior to screening.
13. Any elective surgery requiring hospitalization planned during the study period.

14. Clinically significant major organ disorder at the time of screening including:

    1. Uncontrolled hypertension, defined as stage 2 hypertension by Joint National Committee VII (even if therapy is ongoing, blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic).
    2. Uncontrolled hyperlipidemia (even if therapy is ongoing, LDL >160 mg/dL or triglycerides >500 mg/dL).
    3. Uncontrolled hyperthyroidism or hypothyroidism (subjects can be included if these conditions are controlled with thyroid hormones or anti-thyroid drugs).
    4. Impaired hepatic function (alanine transaminase [ALT] or aspartate transaminase [AST] value >2 times the upper limit of the reference range and/or serum bilirubin 1.5 times the upper limit of the reference range at the screening visit). Subjects with evidence of Gilberts disease may be included in the study if they have total bilirubin of <3 mg/dL with indirect bilirubin contributing to >80% of the total bilirubin.

15. History of a significant medical condition, such as:

    1. Clinically significant cardiac disease like unstable angina, myocardial infarction, grade 3 or 4 congestive heart failure (CHF) according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, and pulmonary hypertension; during the year prior to screening.
    2. Stroke or transient ischemic attack (TIA) in the 6 months before screening.
16. Subjects with major depressive illness in the last 3 years (those who have well-controlled depression for 3 months on a stable dose of antidepressants, with no major depressive episodes in the last 3 years, can be included, even if they are on medication), subjects with history of other severe psychiatric diseases (manic depressive psychosis [MDP], schizophrenia), which in the opinion of the investigator precludes the subject from participating in the study (recorded while collecting subject history).
17. History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, sickle cell anemia, etc.).

18. Subjects using the following in the 3 months prior to screening:

    1. Insulin pump therapy
    2. Any anti-diabetic drugs other than the study insulins allowed by the protocol.
19. Moderate insulin resistance, defined as requiring insulin of ≥1.5 U/IU/kg/day.
20. Subjects who have received ≥14 consecutive days of glucocorticoid therapy by oral, intravenous, inhaled or other routes that produce systemic effects within the past 1 year, or who have received steroids by any route (except intra-nasal, intra-ocular, and topical) within the 4 weeks immediately preceding screening.
21. Subjects diagnosed as having cancer (subjects with history of basal cell carcinoma, carcinoma in situ or squamous cell cancer of skin, or in remission >5 years, will be allowed).
22. Subjects who have donated blood or plasma in the 1 month prior to screening

Contacts and Locations

Locations

United States, California

Mylan Investigator Site

Fresno, California, United States, 93720

Mylan Investigator Site

Greenbrae, California, United States, 94904

Mylan Investigator Site

Huntington Beach, California, United States, 92648

Mylan Investigator Site

La Mesa, California, United States, 91942

Mylan Investigator Site

Los Gatos, California, United States, 95032

Mylan Investigator Site

Mission Hills, California, United States, 91345

Mylan Investigator Site

Montclair, California, United States, 91763

Mylan Investigator Site

Northridge, California, United States, 91324

Mylan Investigator Site

Oakland, California, United States, 94607

Mylan Investigator Site

Santa Monica, California, United States, 90404

Mylan Investigator Site

Tarzana, California, United States, 91356

Mylan Investigator Site

Tustin, California, United States, 92780

Mylan Investigator Site

Walnut Creek, California, United States, 94598

United States, Colorado

Mylan Investigator Site

Denver, Colorado, United States, 80246

United States, Florida

Mylan Investigator Site

Bradenton, Florida, United States, 34201

Mylan Investigator Site

Fort Lauderdale, Florida, United States, 33312

Mylan Investigator Site

Fort Myers, Florida, United States, 33912

Mylan Investigator Site

Hialeah, Florida, United States, 33012

Mylan Investigator Site

Maitland, Florida, United States, 32751

Mylan Investigator Site

Miami, Florida, United States, 33126

Mylan Investigator Site

Miami, Florida, United States, 33156

Mylan Investigator Site

Miami, Florida, United States, 33175

Mylan Investigator Site

New Port Richey, Florida, United States, 34652

Mylan Investigator Site

Palm Harbor, Florida, United States, 34684

Mylan Investigator Site

Saint Petersburg, Florida, United States, 33709

Mylan Investigator Site

Spring Hill, Florida, United States, 34609

Mylan Investigator Site

Tampa, Florida, United States, 33634

Mylan Investigator Site

West Palm Beach, Florida, United States, 33401

United States, Georgia

Mylan Investigator Site

Atlanta, Georgia, United States, 30318

Mylan Investigator Site

Columbus, Georgia, United States, 31904

Mylan Investigator Site

Lawrenceville, Georgia, United States, 30045

Mylan Investigator Site

Roswell, Georgia, United States, 30076

United States, Idaho

Mylan Investigator Site

Idaho Falls, Idaho, United States, 83404

Mylan Investigator Site

Meridian, Idaho, United States, 83642

United States, Illinois

Mylan Investigator Site

Springfield, Illinois, United States, 62701

United States, Iowa

Mylan Investigator Site

Council Bluffs, Iowa, United States, 51501

United States, Texas

Mylan Investigator Site

Austin, Texas, United States, 78731

Mylan Investigator Site

Dallas, Texas, United States, 75231

Sponsors and Collaborators

Mylan Inc.

Mylan GmbH

  Study Documents (Full-Text)

Documents provided by Viatris Inc. ( Mylan Inc. ):

Study Protocol  [PDF] January 11, 2018

Statistical Analysis Plan  [PDF] October 18, 2018

More Information

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT03376789
• Other Study ID Numbers: MYL-1501D-3004
• First Posted: December 18, 2017
• Results First Posted: March 3, 2022
• Last Update Posted: March 3, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; MYL-1501D; Hypoglycemic Agents; Physiological Effects of Drugs