Immunosafety Study of Recombinant Human Insulins in Type 1 Diabetics

An Open Label,Randomized,Comparison of the Immunogenicity and Safety of Wockhardt's Human Insulin Basal Bolus Regimen With the Novo Nordisk's Yeast Based Human Insulin Basal Bolus Regimens, Marketed in United States, in Type 1 Diabetics.

Sponsors

Lead Sponsor: Wockhardt

Source Wockhardt
Brief Summary

This is an open label, randomized, parallel group comparison of the immunogenicity safety of Wockhardt's human insulin and isophane insulin compared with the Novo Nordisk's yeast based human insulin products (marketed in USA) in type 1 diabetics.

There are two phases of the study, which are as follows:

1. Phase 1 is a comparative phase in which there will be 2 arms (which are described in the section below).

2. Phase 2 is a follow up phase only applicable to Wosulin Arm.

The study will last for 54 weeks for the patients enrolled in Wosulin arm and approximately 28 weeks for the patients enrolled in the comparator arm.

Two hundred and forty two patients will be enrolled considering an estimated dropout rate of 15% for a sample size of approximately 105 evaluable patients per arm. The total planned enrollment period for this study is approximately 3 months (90 days).

Overall Status Terminated
Start Date March 2011
Completion Date April 2013
Primary Completion Date April 2013
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in HbAlc from baseline to 6 months of treatment between Wosulin arm and Novolin arm(as surrogate indicator of change in insulin antibodies titers between the two treatment arms). 6 months
Secondary Outcome
Measure Time Frame
Correlation between change in HbA1c and change in anti insulin and insulin neutralizing antibodies. 6 months and 12 months
To compare the change from baseline in the level of serum anti insulin antibodies and insulin neutralizing antibodies between the two arms 6 months
Compare the change in Insulin dose between the two arms 3 and 6 months
Correlation of the immunogenicity with hypoglycemia, local allergic reactions and systemic allergic reactions will be evaluated. 6 and 12 months
Enrollment 134
Condition
Intervention

Intervention Type: Biological

Intervention Name: Wosulin (N or 70/30 with R)

Description: Basal bolus conventional Insulin viz. Wosulin (N or 70/30 with R) to be injected subcutaneously.

Arm Group Label: Wosulin (N or 70/30 with R)

Other Name: Wosulin R, Wosulin N, Wosulin 70/30

Intervention Type: Biological

Intervention Name: Novolin® (N or 70/30 with R)

Description: Basal bolus conventional Insulin viz. Novolin® (N or 70/30 with R) to be injected subcutaneously.

Arm Group Label: Novolin® (N or 70/30 with R)

Other Name: Novolin® R, Novolin® N and Novolin® 70/30

Eligibility

Criteria:

Inclusion Criteria:

1. Subjects who understand the nature of the study and are willing to provide written informed consent.

2. Subjects who have been pre-diagnosed as cases of type-1 diabetes (fasting C-peptide < 0.5 nmol/L) and have been on an insulin regimen for at least 12 months prior to inclusion in the trial.

3. Subjects who have been on a stable regimen of recombinant human insulin or analogs for at least 3 months prior to randomization. (A stable regimen is defined as the dose within +/- 10%).

4. Male or female subjects ≥ 18 and < 55 years of age.

5. Subjects with body mass index (BMI) of ≥18.0 to < 35.0 kg/m2

6. Subjects with glycosylated hemoglobin (HbA1c) levels between ≥6.5 and < 9.5%

7. Subjects who are cooperative, reliable, and agree to have regular injections of insulin and are willing to comply with protocol procedures.

8. Female subjects who are not pregnant and non-lactating with adequate protection from conception and fulfilling one of the following criteria are also eligible if within ≥ 18 and < 55 years age limits:

1. Women of childbearing potential on an acceptable method of birth control (including but not limited to barrier-method, contraceptives, or intrauterine device)

2. Women with history of bilateral tubal ligation,

3. Women who have undergone total hysterectomy

4. Women who are two years post-menopausal

9. Subjects who are able to use the self glucose-monitoring device and to self inject insulin.

Exclusion Criteria:

1. Female subjects who are pregnant (as confirmed by a positive urine and serum β-HCG) or are currently breast-feeding.

2. Compromised hepatic or renal function, as shown by but not limited to:

i.Baseline AST or ALT >3 times the upper limit of normal range, and/or ii.Serum Creatinine >2.0 mg/dl and/or iii.BUN >30 mg/dl Abnormal laboratory findings will be discussed with the medical monitor prior to the subject's entry.

3. Employee of Investigator or have direct involvement with trial or other trials under the direction of Investigator.

4. Those treated with other investigational agents or devices within previous 30 days, from screening, have planned use of an investigational drug or device, or have been previously randomized in this trial.

5. History or evidence of allergy to insulin preparations.

6. History or evidence of severe hypoglycemia (severe hypoglycemic episode defined as the subject required glucose, glucagon, orange juice etc administered by a second person)

7. Requirement for total daily dose of insulin is >1.4 units/kg

8. Who have received Wockhardt's (Wosulin) or Novo Nordisk's Insulin (Novolin® R, Novolin® N, Novolin® 70/30, in US and Actrapid® Insulatard®, and Mixtard® in India) during the previous one year.

9. Serum AIA level > 20 microU/ml.

10. Receipt of any insulin of an animal origin during the last 3 years.

11. Currently receiving or have received within the last year any immunomodulators medications, including corticosteroids that would possibly modify antibody generation either at the enrollment or during the course of the study. (Topical/ ophthalmic/intra-articular/nasal spray corticosteroids will be allowed).

12. Hepatitis B or Hepatitis C or HIV positive.

13. Oral hypoglycaemic agent within 4 weeks prior to signing the consent form.

14. Who have undergone pancreatectomy or pancreas/islet cell transplant.

15. Unlikely to comply with the study protocol e.g. unable to return periodically for subsequent visits.

16. History or evidence of active severe proliferative retinopathy, nephropathy and/or neuropathy significant cardiovascular disease, anemia or hemoglobinopathy, uncontrolled hypothyroidism or uncontrolled hyperthyroidism, alcohol or drug abuse or any other medical condition that in the opinion of Investigator can interfere with the study.

17. Judged by the investigator as inappropriate to participate in the study for any reason other than those mentioned above.

Gender: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ashima Bhatia, M.D. Study Director Wockhardt
Location
Facility:
University Clinical Investigators, Inc. dba Diabetes Research Center | Tustin,, California, 92780, United States
International Research Associates | Hialeah, Florida, 33012, United States
The Center for Diabetes and Endocrine Care | Hollywood, Florida, 33021, United States
Baptist Diabetes Associates, PA | Miami, Florida, 33156, United States
Suncoast Clinical Research | New Port Richie, Florida, 34652, United States
Ormond Medical Arts Pharmaceutical Research Center | Ormond Beach, Florida, 32174, United States
Suncoast Clinical Research | Palm Harbor, Florida, 34684, United States
International Clinical Research - US, LLC | Sanford, Florida, 32771, United States
Cotton-O'Neil Clinical Research Center, Diabetes & Endocrinology | Topeka, Kansas, 66606, United States
Kentucky Diabetes Endocrinology Center | Lexington, Kentucky, 40503, United States
Endocrine & Metabolic Consultants | Rockville,, Maryland, 20852, United States
ActivMed Practices and Research | Haverhill, Massachusetts, 01830, United States
Alzohaili Medical Consultants | Dearborn, Michigan, 48124, United States
ActivMed Practices and Research | Rochester, New Hampshire, 03867, United States
University Diabetes & Endocrine Association | Chattanooga, Tennessee, 37411, United States
Sergio Rovner, MD | El Paso, Texas, 79925, United States
Optimum Clinical Research, Inc. | Salt Lake City, Utah, 84102, United States
Dr Rakesh Sahay | Hyderabad, Andhra Pradesh, 500012, India
Dia Care - A Complete Diabetes Care Centre | Ahmedabad, Gujrat, 380015, India
Dr Sanjay Kalra | Karnal, Haryana, 132001, India
Dr Mala Dharmalingam | Bangalore, Karnataka, 560003, India
Bangalore Diabetes Hospital | Bangalore, Karnataka, 560052, India
Dr Sharad Pendsey | Nagpur, Maharashtra, 440012, India
Diabetes Thyroid &Endocrine Centre | Jaipur, Rajasthan, 302006, India
Bhandari's Clinic | Jaipur, Rajasthan, 302015, India
Location Countries

India

United States

Verification Date

August 2013

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Wosulin (N or 70/30 with R)

Type: Experimental

Description: Basal bolus conventional Insulin viz. Wosulin (N or 70/30 with R) to be injected subcutaneously.

Label: Novolin® (N or 70/30 with R)

Type: Active Comparator

Description: Basal bolus conventional Insulin viz. Novolin® (N or 70/30 with R) to be injected subcutaneously.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov