Evaluate the Immunogenicity of a Novel Glucagon Formulation
In recent past years, regulatory agencies such as FDA and EMA have outlined and recommended adoption of a risk-based approach to evaluating and mitigating immune responses to therapeutic proteins that may adversely affect their safety and efficacy. In their recommendations, both transient and persistent antibody responses should be combined to determine the overall immunogenicity of a product in a given condition. In particular, persistent antibodies are of high importance, since patients with persistent antibodies are more likely to experience clinical sequelae in terms of safety and efficacy, while a transient antibody response can resolve without further consequence.
The present study will provide information on immunogenicity of AMG504-1 with regards to the potential development of high antibody titers or neutralizing antibody activity which may lead to loss of efficacy or an increased risk of an adverse reaction.
|Drug-specific Antibodies Hypoglycemia Diabetes Mellitus||Drug: Glucagon IN Drug: Glucagon IM||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
|Official Title:||A Single Center, Randomized, Parallel Safety Study To Evaluate The Immunogenicity Of A Novel Glucagon Formulation Compared To Commercially Available Glucagon Administered By Intramuscular Injection In Adults With Type 1 OR Type 2 Diabetes|
- Immunogenicity data (titers) [ Time Frame: 5 months ]To evaluate the immunogenicity of repeated single doses of glucagon following intranasal (IN) and intramuscular (IM) administration in adults with Type 1 or Type 2 diabetes (T1D or T2D).
- Safety and tolerability [ Time Frame: 5 months ]To evaluate the safety and tolerability of glucagon following IN and IM administration in adults with T1D or T2D.
|Study Start Date:||September 2013|
|Study Completion Date:||January 2015|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Glucagon IM
GlucaGen® HypoKit (Glucagon) 1 mg Powder and solvent for solution for injection Novo Nordisk Canada
Drug: Glucagon IM
1 mg of glucagon solution intramuscularly 3 doses separated by at least 7 days
Experimental: Glucagon IN
AMG504-1 Dry-Mist Nasal Glucagon Powder AMG Medical Inc. Canada
Drug: Glucagon IN
3 mg of glucagon in 30 mg of AMG504-1 dry powder intranasal 3 doses, separated by at least 7 days
AMG105 is a single center, randomized, single dose, laboratory-blinded, parallel design study. The main objective of this study is to evaluate the immunogenicity of repeated single doses of glucagon following intranasal (IN) 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 IN and IM administration in adults with T1D or T2D. A total of seventy-five (75) adult patients with T1D or T2D will be included in the study.
Male and female patients of at least 18 years of age but not older than 70 years with a history of type 1 diabetes or type 2 diabetes of at least 2 years duration, and with a body mass index (BMI) greater than or equal to 18.5 and below or equal to 35 kg/m2 will be selected according to the inclusion and exclusion criteria. They will be in general good health, without late severe complications, according to medical history, physical examination (including vital signs), nasal examination, bilateral anterior rhinoscopy and laboratory tests (biochemistry, hematology, urinalysis) including negative screening of ethanol and drugs of abuse in urine. A 12-lead ECG will be performed. For female patients, a HCG beta serum pregnancy test must be negative.
A single dose of glucagon will be administered in the morning after a 10-hour overnight fast, either by intranasal or intramuscular route, on 3 occasions. The random allocation of each treatment to each subject will be generated using a 2:1 stratification.
Safety and tolerability will be evaluated through the assessment of adverse events, clinical and laboratory examinations.
Descriptive statistics comprising the sample size, mean, median, SD and 95% confidence intervals (CI) of the mean will be used to describe the titer of anti-glucagon antibodies in each treatment group by period. In addition, the number, proportion and associated 95% CI of patients in each treatment group with anti-glucagon antibodies above the limit of detection will be described.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01959334
|Algorithme Pharma Inc.|
|Laval, Quebec, Canada, H7V 4B3|
|Study Director:||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|