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

Phase 2

Completed

Conditions: Hypoglycemia

Interventions: Drug: G-Pen(TM) 1 mg
Drug: Lilly Glucagon(TM) 1 mg
Drug: G-Pen(TM) 0.5 mg

Registration Number: NCT01972152

Lead Sponsor: Xeris Pharmaceuticals

Brief 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.

Detailed Description: 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)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
G-Pen(TM) 1 mg	Lilly Glucagon(TM) 1 mg	G-Pen(TM) (glucagon injection), single 1 mg subcutaneous (SC) injection
G-Pen(TM) 1 mg	G-Pen(TM) 1 mg	G-Pen(TM) (glucagon injection), single 1 mg subcutaneous (SC) injection
G-Pen(TM) 0.5 mg	G-Pen(TM) 0.5 mg	G-Pen(TM) (glucagon injection), single 0.5 mg SC injection
Lilly Glucagon(TM) 1 mg	Lilly Glucagon(TM) 1 mg	Lilly Glucagon(TM) \[glucagon for injection (rDNA origin)\], single 1 mg SC injection
G-Pen(TM) 1 mg	G-Pen(TM) 0.5 mg	G-Pen(TM) (glucagon injection), single 1 mg subcutaneous (SC) injection
Lilly Glucagon(TM) 1 mg	G-Pen(TM) 0.5 mg	Lilly Glucagon(TM) \[glucagon for injection (rDNA origin)\], single 1 mg SC injection
G-Pen(TM) 0.5 mg	G-Pen(TM) 1 mg	G-Pen(TM) (glucagon injection), single 0.5 mg SC injection
G-Pen(TM) 0.5 mg	Lilly Glucagon(TM) 1 mg	G-Pen(TM) (glucagon injection), single 0.5 mg SC injection
Lilly Glucagon(TM) 1 mg	G-Pen(TM) 1 mg	Lilly Glucagon(TM) \[glucagon for injection (rDNA origin)\], single 1 mg SC injection

Primary Outcome Measures

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

Secondary Outcome Measures

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