Pharmacokinetics (PK) and Pharmacodynamics (PD) of Mayne Glucagon for Injection Compared With Glucagen® (Novo Nordisk) in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospira, Inc.
ClinicalTrials.gov Identifier:
NCT00745186
First received: September 2, 2008
Last updated: June 17, 2015
Last verified: June 2015
  Purpose

The purpose of this study is to evaluate the pharmacokinetics and pharmacodynamic bioequivalence and safety of Hospira Glucagon for Injection and GlucaGen® in healthy volunteers.


Condition Intervention Phase
Hypoglycemia
Drug: Glucagen
Drug: Mayne Glucagon
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label, Four Way Crossover Study to Compare the Pharmacokinetics, Pharmacodynamics and Safety After Intramuscular (IM) Administration of Mayne Glucagon for Injection With Glucagen® (Novo Nordisk) in Healthy Volunteers.

Resource links provided by NLM:


Further study details as provided by Hospira, Inc.:

Primary Outcome Measures:
  • Area Under the Curve from Time 0 to the Last Time Point (AUC0-tlast) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: No ]
  • Maximum Glucagon Concentration Observed (Cmax) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: No ]
  • Maximum Blood Glucose Concentration Observed (BG Cmax) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20,25,30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: No ]
  • Time at which Cmax occurs (Tmax) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: No ]
  • Elimination half life (T1/2) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20,25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: No ]
  • Area Under the Curve from Time 0 to the Last Time Point (AUC0-tlast) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: No ]
  • Maximum Glucagon Concentration Observed (Cmax) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: No ]
  • Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: No ]
  • Time at which Cmax occurs (Tmax) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: No ]
  • Elimination half-life (T1/2) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: No ]
  • Time at which Blood Glucose Cmax occurs (BG Tmax) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: Yes ]
  • Area under the curve from time 0 to return to baseline (rtb) for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: Yes ]
  • Maximum absolute Blood Glucose excursion (MAE) from baseline for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: Yes ]
  • Area under the glucose excursion versus time curve from 0 to rtb for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: Yes ]
  • The earliest recorded time of the MAE for 1 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120, 150, 180 and 240 minutes. ] [ Designated as safety issue: Yes ]
  • Maximum Blood Glucose Concentration Observed (BG Cmax) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: Yes ]
  • Time at which Blood Glucose Cmax occurs (BG Tmax) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: Yes ]
  • Area under the curve from time 0 to return to baseline (rtb) for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: Yes ]
  • Maximum absolute Blood Glucose excursion (MAE) from baseline for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: Yes ]
  • Area under the glucose excursion versus time curve from 0 to rtb for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: Yes ]
  • The earliest recorded time of the MAE for 0.2 mg Dose Level [ Time Frame: Pre-dose: 20, 10 and 5 min; Post-dose: 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90 and 120 minutes. ] [ Designated as safety issue: Yes ]

Enrollment: 28
Study Start Date: August 2007
Study Completion Date: March 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Glucagen
Drug: Glucagen
0.2 mg or 1 mg Glucagen single injection
Experimental: 2
Mayne Glucagon
Drug: Mayne Glucagon
0.2 mg or 1 mg Mayne Glucagon

Detailed Description:

Glucagon has been shown to be effective in the treatment of hypoglycemia, low blood sugar levels, in patients with diabetes. It primarily functions as a counter-regulatory hormone by opposing the actions of insulin to maintain blood glucose levels. A major problem for diabetic patients with hypoglycemia is the development of defective counter regulatory responses including reduced or absent glucagon responses to hypoglycemia. Mayne Glucagon for Injection has been developed as an alternative to currently marketed products.

Administration of exogenous glucagon i.e., not produced in the body, has been shown to be effective in the treatment of low blood sugar in patients with diabetes. Mayne has developed a product, Glucagon for Injection, which is an alternative to currently marketed products. The only difference is the source of the active ingredient. The formulation, routes of administration, dosage regimen and indications of Mayne Glucagon for Injection are identical to those currently registered for the marketed product.

A total of 28 healthy volunteers will be recruited into this study at one investigational site.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy Male or female aged 18-50 years inclusive
  • Body weight between 50 - 100 kg and body mass index (BMI) between 18 and 30 kg/m2 or, if outside the range, considered not clinically significant by the investigator
  • Non-smokers or ex-smokers who have not smoked with in the previous 3 months
  • Written informed consent given
  • Willing and able to comply with the requirements of the protocol and available for the planned duration of the study
  • Subject must agree to use an adequate method of contraception during the study and for 12 weeks after the last dose of investigational medicinal product (IMP). Adequate methods of contraception for subject or partner include condoms with spermicide gel, diaphragm with spermicide gel, coil (intrauterine device), surgical sterilisation, subdermal implant, vasectomy, oral contraceptive pill, depot progesterone injections and abstinence. If a volunteer is usually not sexually active but becomes active he/she or their partner must use one of the contraceptive methods listed . Male subjects whose partner is of child bearing potential must ensure that they or their partner use effective contraception for the course of the study and 12 weeks thereafter

Exclusion Criteria:

  • History or presence of any clinically significant findings that, in the opinion of the investigator, would preclude inclusion in the study
  • History or presence of clinical significant gastrointestinal pathology or symptoms, liver or kidney disease or any other condition that might interfere with the absorption, distribution, metabolism or excretion of the drug.
  • Any clinically significant laboratory findings
  • Clinically significant abnormalities in 12-lead electrocardiogram (ECG) results
  • Positive pregnancy test or lactation
  • Participation in any other clinical study using an investigational product or device within the previous 12 weeks
  • Positive human immunodeficiency virus (HIV), Hepatitis B or C test
  • History of drug or alcohol abuse within the past two years or alcohol consumption greater than 21 units per week for males and greater than 14 units per week for females
  • Blood donation of ≥ 500 mL in the previous 12 weeks
  • Hypersensitivity to Glucagon and/or any excipients
  • Use of prescription medicines or St John's Wort in the previous 2 weeks. The use of over-the-counter medicines within 5 days of dosing except those deemed by the investigator not to interfere with the outcome of the study. Vitamins, minerals and nutritional supplements may be taken at the discretion of the investigator. Hormonal contraceptives will be permitted.
  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: NCT00745186

Locations
United Kingdom
Charles River Laboratories
Edinburgh, United Kingdom, EH14 4AP
Sponsors and Collaborators
Hospira, Inc.
Investigators
Principal Investigator: Stuart Mair INC Research
  More Information

No publications provided

Responsible Party: Hospira, Inc.
ClinicalTrials.gov Identifier: NCT00745186     History of Changes
Other Study ID Numbers: GLC061
Study First Received: September 2, 2008
Last Updated: June 17, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015