A phase 3 clinical trial to compare the efficacy and safety of Mylan's Insulin Glargine with commercial Insulin Glargine (Lantus®) in patients with type 1 diabetes

• Register: EUCTR
• Last refreshed on: 13 February 2017
• Main ID: EUCTR2014-000747-32-DE
• Date of registration: 11/08/2014
• Prospective Registration: Yes
• Primary sponsor: MYLAN GmbH
• Public title: A phase 3 clinical trial to compare the efficacy and safety of Mylan's Insulin Glargine with commercial Insulin Glargine (Lantus®) in patients with type 1 diabetes
• Scientific 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 1 DIABETES MELLITUS PATIENTS
• Date of first enrolment: 07/10/2014
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000747-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Czech Republic, Estonia, Germany, Hungary, Latvia, Romania, Slovakia, South Africa, United Kingdom, United States

Contacts

• Name: Julia Moore,Clinical Project Manage
• Affiliation: Mylan, Inc

• Name: Julia Moore,Clinical Project Manage
• Affiliation: Mylan, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written and signed informed consent needs to be provided by patients or their legal representatives before starting any protocol-specific procedures.
2. Male and female patients between the ages of 18 to 65 years, both ages inclusive.
3. Patients with an established diagnosis of T1DM per ADA 2014 criteria who also fulfil the following criteria:
o Initiation of insulin treatment within 6 months of T1DM diagnosis
o Treatment with basal-bolus insulin therapy for at least 1 year before screening
o Fasting plasma C-peptide <0.3 nmol/L at screening
o Patient 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 patient interview during medical history.
6. Glycosylated hemoglobin (HbA1c) =9.5% at screening.
7. Hemoglobin =9.0 g/dL at screening.
8. Patient has the capability of communicating appropriately with the investigator.
9. Patient is able and willing to comply with the requirements of the trial protocol including the 8-point self-monitored blood glucose (SMBG), completion of patient diary records and following a recommended diet and exercise plan for the entire duration of the trial.
10. Female patients 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 trial, through trial completion.
• Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Postmenopausal females must have had no regular menstrual bleeding for at least 1 year prior to screening.
• Female patients who report surgical sterilization must have had the procedure at least 6 months prior to screening.
• All female patients of childbearing potential must have negative pregnancy test results at screening and at clinic visits, as per the SCHEDULE OF ACTIVITIES.
• If female patients have male partners who have undergone vasectomy, the vasectomy must have occurred more than 6 months prior to screening

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 490
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. medical condition or disease that in the investigator’s opinion would place the patient at an unacceptable risk from study participation.
2. hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the trial, OR history of significant allergic drug reactions.
3. use of animal insulin within the last 3 years or use of biosimilar insulin glargine at any time prior.
4. use of a regular immunomodulator therapy in the 1 year prior to screening.
5. autoimmune disorders other than T1DM or insufficiently treated autoimmune thyroid disorders (see also exclusion criteria 15), judged clinically relevant by the investigator
6. =2 episodes of severe hypoglycemia within the 6 months before screening or history of hypoglycemia unawareness, as judged by the investigator.
7. =1 episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening.
8. clinically significant acute bacterial, viral or fungal systemic infections in the last 4 weeks prior to screening
9. Any clinically significant abnormality in ECG or safety laboratory tests conducted at screening and making the patient ineligible for the study (as per investigator).
10. Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg) or hepatitis C (HCVAb) antibodies at screening.
11. History of drug or alcohol dependence or abuse during the 1 year prior to screening.
12. 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 trial period.
13. Following secondary complications of diabetes:
• Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy/retinal photography examination performed within the 6 months prior to screening (by a person legally authorized to do so).
• Clinical nephrotic syndrome or diabetic nephropathy with a serum creatinine level >1.5 times of upper limit of reference range at screening
• Severe form of neuropathy or cardiac autonomic neuropathy. Patients with mild or moderate forms of neuropathy will be allowed.
• history of limb amputation as a complication of diabetes (at any time), or any vascular procedure during the 1 year prior to screening.
• diabetic foot or diabetic ulcers in the 1 year prior to screening.
14. Any elective surgery requiring hospitalization planned during the trial period.
15. Clinically significant major organ disorder at the time of screening including:
• Uncontrolled hypertension
• Uncontrolled hyperlipidemia
• Uncontrolled hyperthyroidism or hypothyroidism
• Impaired hepatic function. Patients with evidence of Gilberts disease may be included in the trial if they have total bilirubin of <3 mg/dL with indirect bilirubin contributing to >80% of the total bilirubin.
16. History of a significant medical condition, such as:
• 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.
• Stroke or transient ischemic attack (TIA) in the 6 months before screening.
17. Pa

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 1 Diabetes Mellitus
MedDRA version: 19.0 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: BASALOG
Product Name: Mylan's Insulin glargine
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: INSULIN GLARGINE
CAS Number: 160337-95-1
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Lantus Solostar
Product Name: Lantus Solostar
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: INSULIN GLARGINE
CAS Number: 160337-95-1
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To test whether Mylan’s insulin glargine once daily is non-inferior to Lantus® once daily (based on change in HbA1c from baseline to 24 weeks) when administered in combination with mealtime insulin lispro.

Primary end point(s): Change in HbA1c from baseline to 24 weeks

Secondary Objective: To compare Mylan’s insulin glargine to Lantus®, at 24 weeks and 52 weeks, when administered in combination with mealtime insulin lispro with respect to:
1. Immunogenicity: incidence and change from baseline in the relative
levels of ADA, incidence and change from baseline the relative levels of
anti-HCP antibodies
2. Rate per 30 days of hypoglycemic events.
3. Occurrence of local reactions, systemic reactions and other adverse events
4. Device-related safety assessment
5. Change in HbA1c from baseline at other scheduled visits
6. Change in fasting plasma glucose from baseline
7. Change in basal insulin dose per unit body weight (U/kg) from baseline
8. Change in 8-point SMBG profile from baseline
9. Proportion of participants with HbA1c <7% at 24 weeks

Timepoint(s) of evaluation of this end point: at study week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. At screening, and at study weeks 0, 2, 4, 12, 24, 36 and 52
2. every 30 days
3. at each study visit
4. at each study visit
5. at screening and at study weeks 0, 12, 36 and 52
6. at screening and at study weeks -6, -4, -2, 0, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52
7. at each study visit
8. at each study visit
9. at study week 24

Secondary end point(s): 1. Immunogenicity: incidence and change from baseline in the relative
levels of ADA, incidence and change from baseline the relative levels of
anti-HCP antibodies
2. Rate per 30 days of hypoglycemic events.
3. Occurrence of local reactions, systemic reactions and other adverse events
4. Device-related safety assessment
5. Change in HbA1c from baseline at other scheduled visits
6. Change in fasting plasma glucose from baseline
7. Change in basal insulin dose per unit body weight (U/kg) from baseline
8. Change in 8-point SMBG profile from baseline
9. Proportion of participants with HbA1c <7% at 24 weeks

Secondary ID(s)

MYL-GAI-3001

2014-000747-32-SK

105279

Source(s) of Monetary Support

MYLAN GmbH