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Immunosafety Study of Recombinant Human Insulins in Type 1 Diabetics

This study has been terminated.
(Business reasons)
Sponsor:
Information provided by (Responsible Party):
Wockhardt
ClinicalTrials.gov Identifier:
NCT01308437
First received: February 9, 2011
Last updated: August 21, 2013
Last verified: August 2013
  Purpose

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).


Condition Intervention Phase
Type I Diabetes
Biological: Wosulin (N or 70/30 with R)
Biological: Novolin® (N or 70/30 with R)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Wockhardt:

Primary Outcome Measures:
  • 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). [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation between change in HbA1c and change in anti insulin and insulin neutralizing antibodies. [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
    Insulin dose will be used as a covariate

  • To compare the change from baseline in the level of serum anti insulin antibodies and insulin neutralizing antibodies between the two arms [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Compare the change in Insulin dose between the two arms [ Time Frame: 3 and 6 months ] [ Designated as safety issue: No ]
    Glycated hemoglobin levels and the number of hypoglycemic episodes will be the covariants for this analysis

  • Correlation of the immunogenicity with hypoglycemia, local allergic reactions and systemic allergic reactions will be evaluated. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: Yes ]
    Immunogenicity is measured as percentage change in serum antiinsulin antibodies and insulin neutralizing antibodies.


Enrollment: 134
Study Start Date: March 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Wosulin (N or 70/30 with R)
Basal bolus conventional Insulin viz. Wosulin (N or 70/30 with R) to be injected subcutaneously.
Biological: Wosulin (N or 70/30 with R)
Basal bolus conventional Insulin viz. Wosulin (N or 70/30 with R) to be injected subcutaneously.
Other Name: Wosulin R, Wosulin N, Wosulin 70/30
Active Comparator: Novolin® (N or 70/30 with R)
Basal bolus conventional Insulin viz. Novolin® (N or 70/30 with R) to be injected subcutaneously.
Biological: Novolin® (N or 70/30 with R)
Basal bolus conventional Insulin viz. Novolin® (N or 70/30 with R) to be injected subcutaneously.
Other Name: Novolin® R, Novolin® N and Novolin® 70/30

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01308437

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

No publications provided

Responsible Party: Wockhardt
ClinicalTrials.gov Identifier: NCT01308437     History of Changes
Other Study ID Numbers: P3-WOS-IMS-01
Study First Received: February 9, 2011
Last Updated: August 21, 2013
Health Authority: United States: Food and Drug Administration
India: Central Drugs Standard Control Organization

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Autoimmune Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014