Clinical trial NCT01972152: Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of G-Pen(TM) (Glucagon Injection) to Treat Severe Hypoglycemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypoglycemia
Keywords: Hypoglycemia
Glucagon
Lead sponsor: Xeris Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Emissary International LLC
First posted: 2013-10-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: Serious Adverse Events
timeFrame: From first dose until completion of the post-treatment follow-up visit, up to 6 weeks
Secondary outcomes:
measure: Glucose Area Under the Curve (AUC)
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucose Cmax
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucose Tmax
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucose AUCex
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucose MAE
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucose Tex
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucagon AUC
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucagon Cmax
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
measure: Glucagon Tmax
timeFrame: Approximately 15 minutes before each injection and at 5, 10, 15, 20, 30, 45, 60, 120 and 240 minutes post-injection
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Texas Diabetes Institute, University Health System
state: Texas
Study officials:
affiliation: Texas Diabetes Institute, University Health System
name: Ralph A DeFronzo, MD
role: PRINCIPAL_INVESTIGATOR
References: