Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of G-Pen(TM) (Glucagon Injection) to Treat Severe Hypoglycemia
Condition: Hypoglycemia
MeSH terms: Hypoglycemia
Intervention: G-Pen(TM) 1 mg; Lilly Glucagon(TM) 1 mg; G-Pen(TM) 0.5 mg
Intervention MeSH terms: Glucagon
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hypoglycemia; Glucagon

Summary:

      The purpose of this study is to demonstrate that G-Pen(TM) glucagon is comparable to Lilly
      Glucagon(TM) in terms of safety and efficacy, as a treatment for severe hypoglycemia, a
      complication of diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male or female subjects between the ages of 18 and 60 years of age, inclusive,
             at Screening.

          2. Women must be of non-childbearing potential as defined by one of the following:

               -  Females who are >45 and < 60 years of age at Screening and amenorrheic for at
                  least 2 years

               -  Females who have had a documented hysterectomy and/or bilateral oophorectomy.

          3. Females of childbearing potential with a negative pregnancy test at Screening and
             Treatment visits, using one of the following forms of contraception for the duration
             of participation in the study (i.e., until Follow-up 7-14 days post last dose):

               -  Oral contraceptive

               -  Injectable progesterone

               -  Subdermal implant

               -  Spermicidal foam/gel/film/cream/suppository

               -  Diaphragm with spermicide

               -  Copper or hormonal containing intrauterine device (IUD)

               -  Sterile male partner vasectomized > 6 month pre-dosing.

          4. Male subjects are required to use a condom and one of the methods of contraception in
             2. or 3. above starting at Randomization and for the duration of the study.

          5. Evidence of a personally signed and dated informed consent document indicating that
             the subject has been informed of all pertinent aspects of the study.

          6. Subjects must be willing and able to comply with scheduled visits, treatment,
             laboratory tests and study procedures.

        Exclusion Criteria:

          1. Recent (i.e., within three (3) months prior to Screening) evidence or medical history
             of unstable concurrent disease such as: documented evidence or history of clinically
             significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular,
             hepatic, psychiatric, immunological, or clinically significant neurological disease.

          2. Mean of triplicate set of seated BP readings at Screening, confirmed by 1 set of
             triplicate at Screening, if deemed necessary where systolic blood pressure (SBP) <90
             or >140 mm Hg, and diastolic blood pressure (DBP) <50 or >90 mm Hg.

          3. Cardiovascular event within 6 months prior to screening such as unstable angina, acute
             coronary syndrome, myocardial infarction, therapeutic coronary procedure (e.g., stent
             placement, Percutaneous Transluminal Coronary Angioplasty (PTCA), Coronary Artery
             By-pass Grafting (CABG)), stroke or transient ischemic attack.

          4. Clinically significant ECG abnormalities.

          5. Study participants who are pregnant at Screening are not eligible for this study.

          6. Breast feeding must be discontinued if a subject wishes to participate in this study.

          7. Positive test for hepatitis B, hepatitis C, or HIV found at Screening.

          8. Positive urine drug test for illicit drugs at Screening.

          9. Allergies to glucagon, glucagon-like products or to any of the excipients in the
             investigational formulation.

         10. Recent (i.e., within three (3) months prior to Screening) administration of glucagon.

         11. Any prior cerebrovascular accident or major permanent neurological damage such as
             aphasia, hemiparesis, or dementia.

         12. Peripheral artery disease with uncontrolled claudication

         13. Current diagnosis or current clinical evidence of any New York Heart Association
             classification of heart failure.

         14. Subjects with any of the following abnormalities in clinical laboratory tests at
             Screening, confirmed by a single repeat, if necessary:

               -  Total bilirubin > 1.5x upper limit of normal (ULN)

               -  aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) ≥
                  2.5x ULN.

               -  Creatinine > 2.5x ULN.

         15. History of regular alcohol consumption as defined by alcohol intake in a quantity
             exceeding 7 drinks per week for females or 14 drinks per week for males, where 1 drink
             = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of
             hard liquor.

         16. Participation in other studies involving administration of an investigational drug or
             device within 30 days or 5 half-lives, whichever is longer, before screening for the
             current study and during participation in the current study.

         17. Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening.

         18. Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or
             investigational product administration or may interfere with the interpretation of
             study results and, in the judgment of the investigator, would make the subject
             inappropriate for entry into this study.