Evaluate the Immunogenicity of a Novel Glucagon Formulation

NCT ID: NCT01959334

Last Updated: 2019-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2013-12-31

Brief Summary

This study provides information on immunogenicity of Nasal Glucagon (AMG504-1) with regards to the potential development of treatment-emergent anti-glucagon antibodies.

Detailed Description

This study is a single center, randomized, laboratory-blinded, three periods, parallel design study.

The main objective of this study is to evaluate the immunogenicity of repeated single doses of glucagon following nasal and intramuscular (IM) administration in adults with Type 1 or Type 2 diabetes (T1D or T2D). The secondary objective is to evaluate the safety and tolerability of glucagon following NG and IM administration in adults with T1D or T2D.

A single dose of glucagon was administered in the morning after a 10-hour overnight fast, either by intranasal or intramuscular route, on 3 occasions. Each drug administration was separated by at least seven calendar days. Patients were randomized in a 2:1 ratio (NG:IMG) to receive NG or IMG at each of the 3 periods.

Blood samples were collected for measurement of anti-glucagon antibodies at screening visit, prior to dosing at Period 3, and at the post-study visit (approximately 4 weeks after the last glucagon administration).

Conditions

Drug-specific Antibodies; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Glucagon IM

Glucagon dose of 1 milligram (mg) administered intramuscularly (IM).

Group Type: ACTIVE_COMPARATOR

Glucagon IM

Intervention Type: DRUG

Nasal Glucagon (NG

Nasal Glucagon (NG) doses of 3 mg administered intra-nasally.

Group Type: EXPERIMENTAL

Nasal Glucagon (NG)

Intervention Type: DRUG

Interventions

Nasal Glucagon (NG)

Intervention Type: DRUG

Glucagon IM

Intervention Type: DRUG

Other Intervention Names

Nasal Glucagon; AMG504-1 Dry-Mist Intranasal Glucagon; LY900018; GlucaGen® HypoKit

Eligibility Criteria

Inclusion Criteria

1. Availability for the entire study period

2. Motivated volunteer and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee

3. Male or female patient with a history of Type 1 or Type 2 diabetes of at least 2 years duration

4. A female volunteer must meet one of the following criteria:

1. Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the study (from the screening visit until study completion). Additionally, if the participant is using systemic contraceptives, she must use an additional form of acceptable contraception. An acceptable method of contraception includes one of the following:

• Abstinence from heterosexual intercourse
• Systemic contraceptives (birth control pills, injectable/implant /insertable hormonal birth control products, transdermal patch)
• Intrauterine device (with and without hormones)
• Condom with spermicide

or

2. Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses)

5. Volunteer aged of at least 18 years but not older than 70 years

6. Volunteer with a BMI greater than or equal to 18.50 and below 35.00 kg/m2

7. Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before day 1 of this study. An ex- smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study

8. In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations

9. Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer

The informed consent form must be signed by all volunteers, prior to their participation in the study.

Exclusion Criteria

1. Females who are pregnant, actively attempting to get pregnant, or are lactating

2. History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs

3. Presence of significant gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the Investigator could interfere with the absorption, distribution, metabolism or excretion of drugs, or could potentiate or predispose to undesired effects

4. Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases

5. Known presence of rare hereditary problems of galactose and /or lactose intolerance

6. Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)

7. Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors

8. Nasal surgery in the previous 28 days before Day 1 of this study

9. Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this study

10. Use of an immunomodulator medication (including steroids, glucocorticoids, tacrolimus, etc.) in the 28 days before day 1 of this study

11. Any other concomitant maintenance therapy that would influence the outcome of the trial or compromise the safety of the patient, at the discretion of the Investigator and the Sponsor, in the previous 28 days before day 1 of this study

12. Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)

13. Any clinically significant illness in the previous 28 days before day 1 of this study

14. Any history of tuberculosis and/or prophylaxis for tuberculosis

15. Positive urine screening of alcohol and/or drugs of abuse

16. Females who are pregnant according to a positive pregnancy test

17. Concurrent participation or intention of participating in another clinical trial during this study

18. Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study

19. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study

No participants will be allowed to enroll in this study more than once (i.e. if the study is conducted with more than 1 group).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Locemia Solutions ULC

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Algorithme Pharma Inc.

Laval, Quebec, Canada

Countries

Canada

Other Identifiers

I8R-MC-IGBF

Identifier Type: OTHER

Identifier Source: secondary_id

AMG105

Identifier Type: OTHER

Identifier Source: secondary_id

16426

Identifier Type: -

Identifier Source: org_study_id