poglycemic agent used to treat severe hypoglycemia. Glucagon is a singlechainpolypeptide containing 29 amino acid residues and has a molecular weight of 3483, and is identical tohuman glucagon.
Its molecular formula is C153H225N43O49S, with the following molecular structure:
BAQSIMI is a preservative-free, white powder for intranasal administration in an intranasal device containing onedose of 3 mg glucagon. BAQSIMI contains glucagon as the active ingredient and betadex, anddodecylphosphocholine as the excipients.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulatingglycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagonto produce an antihypoglycemic effect.
12.2 Pharmacodynamics
After administration of BAQSIMI in adult patients with diabetes, the mean maximum glucose increase frombaseline was 140 mg/dL (Figure 1).
In pediatric patients with type 1 diabetes (4 to <17 years), the mean maximum glucose increase from baseline was138 mg/dL (4 to <8 years), 133 mg/dL (8 to <12 years), and 102 mg/dL (12 to <17 years) (Figure 2).
Sex and body weight had no clinically meaningful effects on the pharmacodynamics of BAQSIMI.
Common cold with nasal congestion tested with or without use of decongestant did not impact pharmacodynamicsof BAQSIMI.
Figure 1 Mean glucose concentration over time after glucagon dose in adult Type 1 Diabetes patients withinsulin-induced hypoglycemia.
Figure 2 Mean glucose concentration over time in pediatric Type 1 Diabetes patients administered BAQSIMI
12.3 Pharmacokinetics
Absorption
Glucagon absorption via the intranasal route, achieved mean peak plasma levels of 6130 pg/mL at around 15minutes.
Distribution
The apparent volume of distribution was approximately 885 L.
Elimination
The median half-life was approximately 35 minutes.
Metabolism
Glucagon is known to be degraded in the liver, kidneys, and plasma.
Specific Populations
Pediatrics
In pediatric patients (4 to <17 years), glucagon via the intranasal route, achieved mean peak plasma levelsbetween 15 and 20 minutes. The median half-life was 21 to 31 minutes.
Patients with Colds
Common cold with nasal congestion did not impact the pharmacokinetics of BAQSIMI.
Drug Interaction Studies
Common cold with use of decongestant did not impact the pharmacokinetics of BAQSIMI.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies in animals to eva luate carcinogenic potential have not been performed. Recombinant glucagonwas positive in the bacterial Ames assay. It was determined that an increase in colony counts was related totechnical difficulties in running this assay with peptides. Studies in rats have shown that glucagon does not causeimpaired fertility.
14 CLINICAL STUDIES
14.1 Adult Patients
Study 1 (NCT03339453) was a randomized, multicenter, open-label, 2-period, crossover study in adult patientswith type 1 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intramuscularglucagon (IMG). Insulin was used to reduce blood glucose levels to <60 mg/dL. Seventy patients wereenrolled, with a mean age of 41.7 years and a mean diabetes duration of 20.1 years. Twenty-seven (39%) werefemale.
The primary effic |
