Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of G-Pen(TM) (Glucagon Injection) to Treat Severe Hypoglycemia

Study Overview
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Brief Summary
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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.

Detailed Description
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Primary objective: To Evaluate the Safety and Tolerability of G-Pen™ (Glucagon Injection) 1 mg Secondary objective (1): To Evaluate the pharmacodynamics (Efficacy) of G-Pen™ (Glucagon Injection) 1 mg Secondary objective (2):To compare the pharmacokinetics of G-Pen™ (glucagon injection) 1mg [test] administered as 0.5 mg and 1 mg injections, versus Lilly Glucagon™ (glucagon for injection [rDNA origin]) 1 mg (reference)

Official Title
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A RANDOMIZED, PHASE 2, DOUBLE-BLIND, 3-WAY CROSSOVER STUDY WITH G-PEN™ (GLUCAGON INJECTION) TO EVALUATE SAFETY, TOLERABILITY AND COMPARATIVE PHARMACOKINETICS AND PHARMACODYNAMICS TO LILLY GLUCAGON™ (GLUCAGON FOR INJECTION [rDNA ORIGIN]) IN HEALTHY VOLUNTEERS

Conditions
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Hypoglycemia

Intervention / Treatment
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* Drug: G-Pen(TM) 1 mg
* Drug: Lilly Glucagon(TM) 1 mg
* Drug: G-Pen(TM) 0.5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects between the ages of 18 and 60 years of age, inclusive, at Screening. 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. 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. 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. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. Subjects must be willing and able to comply with scheduled visits, treatment, laboratory tests and study procedures. Exclusion Criteria: 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. 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. 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. Clinically significant ECG abnormalities. Study participants who are pregnant at Screening are not eligible for this study. Breast feeding must be discontinued if a subject wishes to participate in this study. Positive test for hepatitis B, hepatitis C, or HIV found at Screening. Positive urine drug test for illicit drugs at Screening. Allergies to glucagon, glucagon-like products or to any of the excipients in the investigational formulation. Recent (i.e., within three (3) months prior to Screening) administration of glucagon. Any prior cerebrovascular accident or major permanent neurological damage such as aphasia, hemiparesis, or dementia. Peripheral artery disease with uncontrolled claudication Current diagnosis or current clinical evidence of any New York Heart Association classification of heart failure. 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. 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. 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. Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-Pen(TM) 1 mg<br>G-Pen(TM) (glucagon injection), single 1 mg subcutaneous (SC) injection | Drug: G-Pen(TM) 1 mg<br> <br> Drug: Lilly Glucagon(TM) 1 mg<br> <br> Drug: G-Pen(TM) 0.5 mg<br> <br> |
| Experimental: G-Pen(TM) 0.5 mg<br>G-Pen(TM) (glucagon injection), single 0.5 mg SC injection | Drug: G-Pen(TM) 1 mg<br> <br> Drug: Lilly Glucagon(TM) 1 mg<br> <br> Drug: G-Pen(TM) 0.5 mg<br> <br> |
| Active Comparator: Lilly Glucagon(TM) 1 mg<br>Lilly Glucagon(TM) [glucagon for injection (rDNA origin)], single 1 mg SC injection | Drug: G-Pen(TM) 1 mg<br> <br> Drug: Lilly Glucagon(TM) 1 mg<br> <br> Drug: G-Pen(TM) 0.5 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events | Number of serious adverse events (SAEs) per treatment group | From first dose until completion of the post-treatment follow-up visit, up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Area Under the Curve (AUC) | Pharmacodynamic parameter: Glucose area under the curve from baseline to 240 minutes post-treatment | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucose Cmax | Pharmacodynamic parameter: Maximum concentration of glucose | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucose Tmax | Pharmacodynamic parameter: Time to Maximum Glucose Concentration | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucose AUCex | Pharmacodynamic parameter: Area Under the Glucose Excursion Curve | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucose MAE | Pharmacodynamic parameter: Maximum absolute glucose excursion from baseline | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucose Tex | Pharmacodynamic parameter: Earliest reported time of MAE, based on within-subject changes from baseline | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucagon AUC | Pharmacokinetic parameter: Glucagon area under the curve from baseline to 240 minutes post-treatment | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucagon Cmax | Pharmacokinetic parameter: Maximum concentration of glucagon | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 
| Glucagon Tmax | Pharmacokinetic parameter: Time to maximum concentration of glucagon | Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoglycemia, Glucagon