BAQSIMI- glucagon powder
For Healthcare Providers >

1. Patient Information
2. Recognition Of Severe Hypoglycemia:
3. Administration:
4. Serious Hypersensitivity:
5. Do Not Use Baqsimi If You:
6. Baqsimi May Cause Serious Side Effects, Including:
7. The Most Common Side Effects Of Baqsimi Include:
8. How Should I Store Baqsimi?
9. Active Ingredient:
10. Inactive Ingredients:

Patient Information ⮝

Advise the patient and family members or caregivers to read the FDA-approved patient labeling (Patient InformationandInstructions for Use).

Recognition Of Severe Hypoglycemia: ⮝

Inform patient and family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia.

Administration: ⮝

Review the Patient Information and Instructions for Use with the patient and family members or caregivers.

Serious Hypersensitivity: ⮝

Inform patients that allergic reactions can occur with BAQSIMI. Advise patients to
BAQSIMI is a prescription medicine used to treat very low blood sugar (severe hypoglycemia) in people with diabetes ages 4 years and above.
It is not known if BAQSIMI is safe and effective in children under 4 years of age.

Do Not Use Baqsimi If You: ⮝

• have a tumor in the gland on top of your kidneys (adrenal gland) called pheochromocytoma.
• have a tumor in your pancreas called insulinoma.
• are allergic to glucagon, or any other ingredients in BAQSIMI.
  
  • Read the detailedInstructions for Usethat comes with BAQSIMI.
  • Use BAQSIMI exactly how your healthcare provider tells you to use it.
  • Make sure your caregiver knows where you keep your BAQSIMI and how to use BAQSIMI the right waybeforeyou need their help.
  • Your healthcare provider will tell you how and when to use BAQSIMI.
  • BAQSIMI contains only 1 dose of medicine andcannotbe reused.
  • BAQSIMI should be given in one side of your nose (nostril) but does not need to be inhaled.
  • BAQSIMI will work even if you have a cold or are taking cold medicine.
  • After giving BAQSIMI, the caregiver should call for emergency medical help right away.
  • If the person does not respond after 15 minutes, another dose may be given, if available.
  • Tell your healthcare provider each time you use BAQSIMI.

Baqsimi May Cause Serious Side Effects, Including: ⮝

• High blood pressure.BAQSIMI can cause high blood pressure in certain people with tumors in their adrenal glands.
• Low blood sugar.BAQSIMI can cause certain people with tumors in their pancreas to have low blood sugar.
• Serious allergic reaction.Call your healthcare provider orget medical help right awayif you have a serious allergic reaction including:

• rash

• difficulty breathing

• low blood pressure

The Most Common Side Effects Of Baqsimi Include: ⮝

• nausea
• vomiting
• headache

• runny nose
• discomfort in your nose
• stuffy nose

• redness in your eyes
• itchy nose, throat and eyes
• watery eyes

These are not all the possible side effects of BAQSIMI. For more information, ask your healthcare provider.
Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How Should I Store Baqsimi? ⮝

• Store BAQSIMI at temperatures up to 86 F (30 C).
• Keep BAQSIMI in the shrink wrapped tube until you are ready to use it.

Keep BAQSIMI and all medicines out of the reach of children.General Information about the safe and effective use of BAQSIMI.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use BAQSIMI for a condition for which it was not prescribed. Do not give BAQSIMI to other people, even if they have the same symptoms that you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about BAQSIMI that is written for healthcare professionals.

Active Ingredient: ⮝

glucagon

Inactive Ingredients: ⮝

betadex and dodecylphosphocholineMarketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
www.baqsimi.com
Copyright 2019, Eli Lilly and Company. All rights reserved.
For more information, call 1-800-LillyRx (1-800-545-5979) or go to the following website: www.baqsimi.com.

BAQ-0001-PPI-20190724

INSTRUCTIONS FOR USE

BAQSIMI

(glucagon) nasal powder

3 mg

Read the Instructions for Use for BAQSIMI before using it.BAQSIMI is used to treat very low blood sugar (severe hypoglycemia) that may cause you to need help from others. You should make sure you show your caregivers, family and friends where you keep BAQSIMI and explain how to use it by sharing these instructions.They need to know how to use BAQSIMI before an emergency happens.

Tube and Device Parts

Important Information to Know

• Do notremove the Shrink Wrap or open the Tube until you are ready to use it.
• If the Tube has been opened, BAQSIMI could be exposed to moisture.This could cause BAQSIMI not to work as expected.
• Do not push the plunger or test BAQSIMI before you are ready to use it.
• BAQSIMI contains 1 dose of glucagon nasal powder andcannotbe reused.
• BAQSIMI is for nasal (nose) use only.
• BAQSIMI will work even if you have a cold or are taking cold medicine.

Preparing the Dose

	Remove the Shrink Wrap by pulling on red stripe.
	Open the Lid and remove the Device from the Tube. Caution: Do not press the Plunger until ready to give the dose.

Giving the Dose

	Hold Devicebetween fingers and thumb. Do notpush Plunger yet.
	Insert Tipgently into one nostril until finger(s) touch the outside of the nose.
	Push Plungerfirmly all the way in. Dose is complete when the Green Line disappears.

After giving BAQSIMI

• Call for emergency medical help right away.
• If the person is unconscious turn the person on their side.
• Throw away the used Device and Tube.
• Encourage the person to eat as soon as possible. When they are able to safely swallow, give the person a fast acting source of sugar, such as juice. Then encourage the person to eat a snack, such as crackers with cheese or peanut butter.
• If the person does not respond after 15 minutes, another dose may be given, if available.

Storage and Handling

• Do not remove the Shrink Wrap or open the Tube until you are ready to use it.
• Store BAQSIMI in the shrink wrapped Tube at temperatures up to 86 F (30 C ).
• Replace BAQSIMI before the expiration date printed on the Tube or carton.

Other Information

• Caution: Replace the used BAQSIMI right away so you will have a new BAQSIMI in case you need it.
• Keep BAQSIMI and all medicines out of the reach of children.

For Questions or More Information about BAQSIMI

• Call your healthcare provider
• Call Lilly at 1-800-Lilly-Rx (1-800-545-5979)
• Visit www.baqsimi.com

BAQSIMI is a trademark of Eli Lilly and Company.

Marketed by: Lilly USA, LLC

Indianapolis, IN 46285, USA

Copyright 2019, Eli Lilly and Company. All rights reserved.

BAQSIMI Device meets all applicable requirements defined in ISO 20072

This Instructions for Use has been approved by the U.S. Food and Drug Adminstration
Issued: July 2019
BAQ-0001-IFU-20190724

1. Highlights Of Prescribing Information
2. Indications And Usage
3. Dosage And Administration
4. Dosage Forms And Strengths
5. Contraindications
6. Warnings And Precautions
7. Adverse Reactions
8. Drug Interactions
9. 1 Indications And Usage
10. 2 Dosage And Administration
11. 3 Dosage Forms And Strengths
12. 4 Contraindications
13. 5 Warnings And Precautions
14. 6 Adverse Reactions
15. 7 Drug Interactions
16. 8 Use In Specific Populations
17. 10 Overdosage
18. 11 Description
19. 12 Clinical Pharmacology
20. 13 Nonclinical Toxicology
21. 14 Clinical Studies
22. 16 How Supplied/storage And Handling
23. Package Label Baqsimi 3 Mg Nasal Powder Two Pack

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use BAQSIMI safely and effectively. See full prescribing information for BAQSIMI.
BAQSIMI (glucagon) nasal powder
Initial U.S. Approval: 1960

Indications And Usage ⮝

BAQSIMI is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in patients with diabetes ages 4 years and above. (1)

Dosage And Administration ⮝

• BAQSIMI is for intranasal use only. (2.1)
• The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril. (2.2)
• Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use. (2.1)
• Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled. (2.1)
• Call for emergency assistance immediately after administering the dose. (2.1)
• When the patient responds to treatment, give oral carbohydrates. (2.1)
• Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. (2.1)
• If there has been no response after 15 minutes, an additional 3 mg dose may be administered while waiting for emergency assistance. (2.2)

Dosage Forms And Strengths ⮝

Nasal powder: intranasal device containing one dose of glucagon 3 mg (3)

Contraindications ⮝

• Pheochromocytoma (4)
• Insulinoma (4)
• Known hypersensitivity to glucagon or to any of the excipients (4)

Warnings And Precautions ⮝

• Catecholamine Release in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because BAQSIMI may stimulate the release of catecholamines from the tumor. (4, 5.1)
• Lack of Efficacy in Patients with Insulinoma: In patients with insulinoma, administration may produce an initial increase in blood glucose; however, BAQSIMI may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of BAQSIMI, give glucose orally or intravenously. (4, 5.2)
• Hypersensitivity and Allergic Reactions: Allergic reactions have been reported and include generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension. (4, 5.3)
• Lack of Efficacy in Patients with Decreased Hepatic Glycogen: BAQSIMI is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for BAQSIMI to be effective. Patients with these conditions should be treated with glucose. (5.4)

Adverse Reactions ⮝

Most common ( 10%) adverse reactions associated with BAQSIMI are nausea, vomiting, headache, upper respiratory tract irritation (i.e., rhinorrhea, nasal discomfort, nasal congestion, cough, and epistaxis), watery eyes, redness of eyes, itchy nose, throat and eyes. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions ⮝

• Beta-blockers: Patients taking beta-blockers may have a transient increase in pulse and blood pressure. (7.1)
• Indomethacin: In patients taking indomethacin BAQSIMI may lose its ability to raise glucose or may produce hypoglycemia. (7.2)
• Warfarin: BAQSIMI may increase the anticoagulant effect of warfarin. (7.3)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 7/2019

1 Indications And Usage  ⮝

BAQSIMI is indicated for the treatment of severe hypoglycemia in patients with diabetes ages 4 years and above.

2 Dosage And Administration  ⮝

2.1 Important Administration Instructions

BAQSIMI is for intranasal use only.

Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. Because severe hypoglycemia requires help of others to recover, instruct the patient to inform those around them about BAQSIMI and its Instructions for Use. Administer BAQSIMI as soon as possible when severe hypoglycemia is recognized.

Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for BAQSIMI. Emphasize the following instructions to the patient or caregiver:

• Do not push the plunger or test the device prior to administration.
• Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use.
• Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled.
• Call for emergency assistance immediately after administering the dose.
• When the patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia.
• Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused.

2.2 Dosage in Adults and Pediatric Patients Aged 4 Years and Above

The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril.

If there has been no response after 15 minutes, an additional 3 mg dose of BAQSIMI from a new device may be administered while waiting for emergency assistance.

3 Dosage Forms And Strengths  ⮝

Nasal Powder:

• 3 mg glucagon: as a white powder in an intranasal device containing one dose of glucagon

4 Contraindications  ⮝

BAQSIMI is contraindicated in patients with:

• Pheochromocytoma [see Warnings and Precautions (5.1)]
• Insulinoma [see Warnings and Precautions (5.2)]
• Known hypersensitivity to glucagon or to any of the excipients in BAQSIMI. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions (5.3)]

5 Warnings And Precautions  ⮝

5.1 Catecholamine Release in Patients with Pheochromocytoma

BAQSIMI is contraindicated in patients with pheochromocytoma because glucagon may stimulate release of catecholamines from the tumor [see Contraindications (4)]. If the patient develops a dramatic increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure.

5.2 Lack of Efficacy in Patients with Insulinoma

In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, BAQSIMI administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. BAQSIMI is contraindicated in patients with insulinoma [see Contraindications (4)]. If a patient develops symptoms of hypoglycemia after a dose of BAQSIMI, give glucose orally or intravenously.

5.3 Hypersensitivity and Allergic Reactions

Allergic reactions have been reported with glucagon, these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. BAQSIMI is contraindicated in patients with a prior hypersensitivity reaction [see Contraindications (4)].

5.4 Lack of Efficacy in Patients with Decreased Hepatic Glycogen

BAQSIMI is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for BAQSIMI administration to be effective. Patients with these conditions should be treated with glucose.

6 Adverse Reactions  ⮝

The following serious adverse reactions are described below and elsewhere in labeling:

• Hypersensitivity and Allergic Reactions [see Warnings and Precautions (5.3)].

6.1 Clinical Trial Data

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of BAQSIMI cannot be directly compared with rates in clinical trials of other drugs and may not reflect the rates observed in practice.

Adverse Reactions in Adult Patients

Two similarly designed comparator-controlled trials, Study 1 and Study 2, evaluated the safety of a single dose of BAQSIMI compared to a 1 mg dose of intra-muscular glucagon (IMG) in adult patients with diabetes [see Clinical Studies (14)].

Table 1 presents adverse reactions that occurred with BAQSIMI at an incidence of 2% in a pool of Study 1 and Study 2.

Table 1: Pooled Adverse Reactions ( 2%) in Adult Patients with Type 1 and Type 2 Diabetes in Study 1 and Study 2

a Upper Respiratory Tract Irritation: rhinorrhea, nasal discomfort, nasal congestion, cough, and epistaxis.
Adverse Reaction	BAQSIMI 3 mg (N=153) %
Nausea	26.1
Headache	18.3
Vomiting	15.0
Upper Respiratory Tract Irritationa	12.4

Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in Study 1 and 2 and these adverse reactions are presented in Table 2.

Table 2: Solicited Nasal and Non-Nasal Adverse Reactions in Adult Patients with Type 1 and Type 2 Diabetes Pooled from Study 1 and 2

a Subjects were asked to report whether they have the symptom, as well as severity (mild, moderate, severe) at baseline, and after glucagon administration.
Adverse Reactiona	BAQSIMI 3 mg (n=153) %
	Any increase in symptom severitya
Watery eyes	58.8
Nasal congestion	42.5
Nasal itching	39.2
Runny nose	34.6
Redness of eyes	24.8
Itchy eyes	21.6
Sneezing	19.6
Itching of throat	12.4
Itching of ears	3.3

Adverse Reactions in Pediatric Patients Aged 4 Years and Above

A single dose of BAQSIMI was compared to weight-based doses of 0.5 mg or 1 mg of IMG in pediatric patients with type 1 diabetes in Study 3 [see Clinical Studies (14)].

Table 3 presents adverse reactions that occurred with BAQSIMI in pediatric patients at an incidence of 2% in Study 3.

Table 3: Adverse Reactions ( 2%) Occurring in Pediatric Patients with Type 1 Diabetes in Study 3

a Upper Respiratory Tract Irritation: nasal discomfort, nasal congestion, sneezing.
Adverse Reaction	BAQSIMI 3 mg (n=36) %
Vomiting	30.6
Headache	25.0
Nausea	16.7
Upper Respiratory Tract Irritationa	16.7

Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in pediatric patients in Study 3 and these adverse reactions are presented in Table 4.

Table 4: Solicited Nasal and Non-Nasal Adverse Reactions in Pediatric Patients with Type 1 Diabetes in Study 3

a Subjects were asked to report whether they have the symptom, as well as severity (mild, moderate, severe) at baseline, and after glucagon administration.
Adverse Reactiona	BAQSIMI 3 mg (n=36) %
	Any increase in symptom severitya
Watery eyes	47.2
Nasal congestion	41.7
Nasal itching	27.8
Runny nose	25.0
Sneezing	19.4
Itchy eyes	16.7
Redness of eyes	13.9
Itching of throat	2.8
Itching of ears	2.8

Other Adverse Reactions in Adult and Pediatric Patients

Other observed adverse reactions with BAQSIMI-treated patients across clinical trials were, dysgeusia, pruritus, tachycardia, hypertension, and additional upper respiratory tract irritation events (nasal pruritus, throat irritation, and parosmia).

6.2 Immunogenicity

As with all therapeutic peptides, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to BAQSIMI with the incidences of antibodies to other products may be misleading.

In 3 clinical trials, 3/124 (2%) of BAQSIMI-treated patients had treatment-emergent anti-drug antibodies as detected by an affinity capture elution (ACE) ligand-binding immunogenicity assay. No neutralizing antibodies were detected.

7 Drug Interactions  ⮝

7.1 Beta-blockers

Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given BAQSIMI.

7.2 Indomethacin

In patients taking indomethacin, BAQSIMI may lose its ability to raise blood glucose or may even produce hypoglycemia.

7.3 Warfarin

BAQSIMI may increase the anticoagulant effect of warfarin.

8 Use In Specific Populations  ⮝

8.1 Pregnancy

Risk Summary

Available data from case reports and a small number of observational studies with glucagon use in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across the human placental barrier during early gestation. In a rat reproduction study, no embryofetal toxicity was observed with glucagon administered by injection during the period of organogenesis at doses representing up to 40 times the human dose, based on body surface area (mg/m2) (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In pregnant rats given animal sourced glucagon twice-daily by injection at doses up to 2 mg/kg (up to 40 times the human dose based on body surface area extrapolation, mg/m2) during the period of organogenesis, there was no evidence of increased malformations or embryofetal lethality.

8.2 Lactation

Risk Summary

There is no information available on the presence of glucagon in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. However, glucagon is a peptide and would be expected to be broken down to its constituent amino acids in the infant's digestive tract and is therefore, unlikely to cause harm to an exposed infant.

8.4 Pediatric Use

The safety and effectiveness of BAQSIMI for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients ages 4 years and above. Use of BAQSIMI for this indication is supported by evidence from a study in 48 pediatric patients from 4 to <17 years of age with type 1 diabetes mellitus. [see Clinical Studies (14.2)].

The safety and effectiveness of BAQSIMI have not been established in pediatric patients younger than 4 years of age.

8.5 Geriatric Use

Clinical studies of BAQSIMI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Limited clinical trial experience has not identified differences in responses between the elderly and younger patients.

10 Overdosage  ⮝

If overdosage occurs, the patient may experience nausea, vomiting, inhibition of GI tract motility, increase in blood pressure and pulse rate. In case of suspected overdosing, serum potassium levels may decrease and should be monitored and corrected if needed. If the patient develops a dramatic increase in blood pressure, phentolamine mesylate has been shown to be effective in lowering blood pressure for the short time that control would be needed.

11 Description  ⮝

BAQSIMI contains glucagon, an antihypoglycemic agent used to treat severe hypoglycemia. Glucagon is a single-chain polypeptide containing 29 amino acid residues and has a molecular weight of 3483, and is identical to human 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 one dose of 3 mg glucagon. BAQSIMI contains glucagon as the active ingredient and betadex, and dodecylphosphocholine as the excipients.

12 Clinical Pharmacology  ⮝

12.1 Mechanism of Action

Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect.

12.2 Pharmacodynamics

After administration of BAQSIMI in adult patients with diabetes, the mean maximum glucose increase from baseline was 140 mg/dL (Figure 1).

In pediatric patients with type 1 diabetes (4 to <17 years), the mean maximum glucose increase from baseline was 138 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 pharmacodynamics of BAQSIMI.

Figure 1 Mean glucose concentration over time after glucagon dose in adult Type 1 Diabetes patients with insulin-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 15 minutes.

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 levels between 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 evaluate carcinogenic potential have not been performed. Recombinant glucagon was positive in the bacterial Ames assay. It was determined that an increase in colony counts was related to technical difficulties in running this assay with peptides. Studies in rats have shown that glucagon does not cause impaired fertility.

14 Clinical Studies  ⮝

14.1 Adult Patients

Study 1 (NCT03339453) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to <60 mg/dL. Seventy patients were enrolled, with a mean age of 41.7 years and a mean diabetes duration of 20.1 years. Twenty-seven (39%) were female.

The primary efficacy outcome measure was the proportion of patients achieving treatment success, which was defined as either an increase in blood glucose to 70 mg/dL or an increase of 20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level. Glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes, following glucagon administration.

The mean nadir blood glucose was 54.5 mg/dL for BAQSIMI and 55.8 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 100% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success. The mean time to treatment success was 11.6 and 9.9 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively.

Table 5: Adult Patients with Type 1 Diabetes Meeting Treatment Success and Other Glucose Criteria in Study 1

a The Efficacy Analysis Population consisted of all patients who received both doses of the Study Drug with evaluable primary outcome.
b Difference calculated as (percentage with success in BAQSIMI) (percentage with success in IMG).
c 2-sided 95% confidence interval (CI) of paired differences using a Wald-Min correction; non-inferiority margin = -10%.
	Type 1 Diabetes (N=66)a
	BAQSIMI 3 mg	IMG 1 mg
Treatment Success n (%)	66 (100%)	66 (100%)
Treatment Difference (2-sided 95% confidence limit)b, c	0% (-2.9%, 2.9%)
Glucose criterion met n (%)
(i) 70 mg/dL (ii) Increase by 20 mg/dL from nadir Both (i) and (ii)	66 (100%) 66 (100%) 66 (100%)	66 (100%) 66 (100%) 66 (100%)

Study 2 (NCT01994746) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes or type 2 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to the hypoglycemic range with a target blood glucose nadir of <50 mg/dL.

Study 2 enrolled 83 patients 18 to <65 years of age. The mean age of patients with type 1 diabetes (N=77) was 32.9 years and a mean diabetes duration of 18.1 years, and 45 (58%) patients were female. The mean age of patients with type 2 diabetes (N=6) was 47.8 years, with a mean diabetes duration of 18.8 years, and 4 (67%) patients were female.

The mean nadir blood glucose was 44.2 mg/dL for BAQSIMI and 47.2 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 98.8% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success within 30 minutes.

The mean time to treatment success was 15.9 and 12.1 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively.

Table 6: Adult Patients with Type 1 and Type 2 Diabetes Meeting Treatment Success and Other Glucose Criteria in Study 2

a The Efficacy Analysis Population consisted of all patients who received both doses of the Study Drug with evaluable primary outcome.
b Difference calculated as (percentage with success in BAQSIMI) (percentage with success in IMG).
c 2-sided 95% confidence interval (CI) of paired differences using a Wald-Min correction; non-inferiority margin = -10%.
d Percentage based on number of patients.
	Type 1 and Type 2 Diabetes (N=80)a
	BAQSIMI 3 mg	IMG 1 mg
Treatment Success n (%)	79 (98.8%)	80 (100%)
Treatment Difference (2-sided 95% confidence limit) b,c	-1.3% (-4.6%, 2.2%)
Glucose criterion met n (%)d
(i) 70 mg/dL	77 (96%)	79 (99%)
(ii) Increase by 20 mg/dL from nadir	79 (99%)	80 (100%)
Both (i) and (ii)	77 (96%)	79 (99%)

14.2 Pediatric Patients

Study 3 (NCT01997411) was a randomized, multicenter, clinical study that assessed BAQSIMI compared to intra-muscular glucagon (IMG) in pediatric patients aged 4 years and older with type 1 diabetes. Insulin was used to reduce blood glucose levels, and glucagon was administered after glucose reached <80 mg/dL. Efficacy was assessed based on percentage of patients with a glucose increase of 20 mg/dL from glucose nadir within 30 minutes following BAQSIMI administration.

Forty-eight patients were enrolled and received at least one dose of study drug. The mean age in the Young Children cohort (4 to <8 years) was 6.5 years. In the Children cohort (8 to <12 years), mean age was 11.1 years and in the Adolescents cohort (12 to <17 years) mean age was 14.6 years. In all age cohorts, the population was predominantly male and white.

Across all age groups, all (100%) patients in both treatment arms achieved an increase in glucose 20 mg/dL from glucose nadir within 20 minutes of glucagon administration. The mean time to reach a glucose increase of 20 mg/dL for BAQSIMI and IMG for all age groups is shown in Table 7.

Table 7: Mean Time to Reach Glucose Increase of 20 mg/dL from Nadir in Pediatric Patients with Type 1 Diabetes in Study 3

Increase from Nadir	Mean Time Post-Glucagon Administration (minutes)
	Young Children (4 to <8 years old)		Children (8 to <12 years old)		Adolescents (12 to <17 years old)
	IMGa N=6	BAQSIMI 3 mg N=12	IMGa N=6	BAQSIMI 3 mg N=12	IMGa N=12	BAQSIMI 3 mg N=12
a 0.5 mg or 1 mg of IMG (based upon body weight)
20 mg/dL	10.8	10.8	12.5	11.3	12.5	14.2

16 How Supplied/storage And Handling  ⮝

BAQSIMI is supplied as an intranasal device containing one 3 mg dose of glucagon as a preservative free, white powder.

• BAQSIMI One Pack carton contains 1 intranasal device (NDC 0002-6145-11)
• BAQSIMI Two Pack carton contains 2 intranasal devices (NDC 0002-6145-27)
• Store at temperatures up to 86 F (30 C) in the shrink wrapped tube provided.
• Keep BAQSIMI in the shrink wrapped tube until ready to use. If the tube has been opened, BAQSIMI may have been exposed to moisture and may not work as expected.
• Discard BAQSIMI and tube after use.

Package Label Baqsimi 3 Mg Nasal Powder Two Pack  ⮝

NDC 0002-6145-27

baqsimiTM

(glucagon) nasal powder

3 mg

For Treatment of Severe Low Blood Sugar

For Nasal Use Only

Contains 2 nasal devices.

Keep tubes sealed until ready to use.

Rx only

BAQSIMI Two PackTM

www.baqsimi.com

Lilly

BAQSIMI glucagon powder

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0002-6145 Route of Administration NASAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength glucagon (UNII: 76LA80IG2G) (glucagon - UNII:76LA80IG2G) glucagon 3 mg

Inactive Ingredients Ingredient Name Strength Betadex (UNII: JV039JZZ3A) 24 mg Water (UNII: 059QF0KO0R) Acetic Acid (UNII: Q40Q9N063P)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0002-6145-11 1 in 1 CARTON 08/06/2019 1 NDC:0002-6145-02 1 in 1 TUBE 1 NDC:0002-6145-01 1 in 1 BOTTLE, UNIT-DOSE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.) 2 NDC:0002-6145-27 2 in 1 CARTON 08/06/2019 2 NDC:0002-6145-02 1 in 1 TUBE 2 NDC:0002-6145-01 1 in 1 BOTTLE, UNIT-DOSE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA210134 07/24/2019

Labeler - Eli Lilly and Company (006421325)

Revised: 8/2019 Document Id: 98533526-09ab-49ae-bd4d-159de774c0d0 34391-3 Set id: 3fdb4e92-2e19-487d-9f14-99871e9fd15a Version: 3 Effective Time: 20190808 Eli Lilly and Company