Evaluate the Immunogenicity of a Novel Glucagon Formulation

NCT01959334 | Completed Phase 3 Results

• 3 other identifiers: 16426I8R-MC-IGBFAMG105
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug-specific Antibodies; Diabetes Mellitus

Keywords

Diabetes Mellitus; Hypoglycemia; Glucagon; Anti-glucagon Antibody; Immunogenicity

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Treatment-emergent Anti-Drug Antibody (ADA)

  Glucagon anti-drug antibodies (ADA) were assessed at baseline through study completion. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)\*100. Treatment-Emergent ADA includes treatment-induced ADA and treatment boosted ADA. Treatment-induced is defined as participants with 'Not Detected' ADA at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is one 2-fold dilution higher than the MRD (minimal required dilution) of the assay. For the nasal glucagon Tier 1-3 ADA screening assay, the MRD is 1:20. Treatment-boosted is defined as Patient with ADA 'Detected' at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is at least (\>or=) 4-fold higher than the baseline titer.

  Baseline through study completion (up to 10 weeks)

• Percentage of Participants With Neutralizing Antibodies

  Baseline through study completion (up to 10 weeks)

• Number of Participants With At Least One Adverse Event

  Safety parameters assessed included the occurrence of adverse events, the measurement of clinical laboratory parameters; vital signs, ECGs, physical examination, blood glucose, and examination of the injection site (following the IM administration). An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

  First dose of study drug through the post-study completion (up to 10 weeks)

Study Arms (2)

Glucagon IM

ACTIVE COMPARATOR

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

Drug: Glucagon IM

Nasal Glucagon (NG

EXPERIMENTAL

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

Drug: Nasal Glucagon (NG)

Interventions

Nasal Glucagon (NG) DRUG

Also known as: Nasal Glucagon, AMG504-1 Dry-Mist Intranasal Glucagon, LY900018

Nasal Glucagon (NG

Glucagon IM DRUG

Also known as: GlucaGen® HypoKit

Glucagon IM

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Availability for the entire study period
• 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
• Male or female patient with a history of Type 1 or Type 2 diabetes of at least 2 years duration
• A female volunteer must meet one of the following criteria:
• 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
• 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)
• Volunteer aged of at least 18 years but not older than 70 years
• Volunteer with a BMI greater than or equal to 18.50 and below 35.00 kg/m2
• 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
• 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
• Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer

You may not qualify if:

• Females who are pregnant, actively attempting to get pregnant, or are lactating
• History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs
• 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
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
• Known presence of rare hereditary problems of galactose and /or lactose intolerance
• Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)
• Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors
• Nasal surgery in the previous 28 days before Day 1 of this study
• Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this study
• Use of an immunomodulator medication (including steroids, glucocorticoids, tacrolimus, etc.) in the 28 days before day 1 of this study
• 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
• Significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the previous 28 days before day 1 of this study
• Any history of tuberculosis and/or prophylaxis for tuberculosis
• Positive urine screening of alcohol and/or drugs of abuse

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Locemia Solutions ULC: collaborator

Study Sites (1)

Algorithme Pharma Inc.

Laval, Quebec, H7V 4B3, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus; Hypoglycemia

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2013
• First Posted: October 10, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: September 6, 2019
• Results First Posted: September 6, 2019

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)