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September 8, 2016


Kaléo Presents Studies at PAINWeek 2016 Comparing Naloxone Intramuscular Injection and Naloxone Intranasal Administration

– Findings from one study demonstrate ease of use with EVZIO® (naloxone HCl injection) Auto-injector compared to an improvised naloxone intranasal kit

– Results from a second study show that a common over-the-counter nasal decongestant negatively impacts absorption of naloxone when administered intranasally

Richmond, Va. (September 8, 2016) – Kaléo, a privately-held pharmaceutical company, today announced findings from two studies comparing intramuscular injection and intranasal administration of naloxone, a drug used for the emergency treatment of opioid overdose. The studies, which represent kaléo’s commitment to advancing the understanding of naloxone use in opioid emergencies, will be presented at PAINWeek 2016 on Thursday, September 8.

In one study (poster #35), non-medically trained participants were asked to administer naloxone using EVZIO® (naloxone HCl injection) Auto-injector and an improvised naloxone intranasal kit during a simulated opioid emergency, with and without prior training on how to use the devices. The study found that 100% and 97.6% of participants were able to administer EVZIO with and without training, respectively, compared to 43.9% and 0% with the improvised naloxone intranasal delivery system, respectively (p<0.0001).

“The results of this study illustrate the importance of incorporating human factors engineering into the design of naloxone products intended for use in the community setting where family, friends and caregivers of those taking an opioid may be in the best position to quickly intervene during a life-threatening opioid emergency.” said Evan Edwards, Vice President, Product Decelopment & Industrialization at kaléo. “This study demonstrates that EVZIO, which was the first naloxone product specifically designed, FDA approved and labeled for use in the community setting based on human factors engineering studies, can play an important role in successful administration of naloxone by a non-medically trained person during a life-threatening opioid emergency.”

The second study (poster #65) compared the pharmacokinetics of 2.0 mg naloxone administered to volunteers with chronic rhinitis by intramuscular injection, intranasal administration, and intranasal administration after treatment with Afrin®, a common over-the-counter nasal decongestant/vasoconstrictor. The pharmacokinetics showed that intranasal naloxone absorption was slower and resulted in overall lower exposure in patients who received Afrin® prior to their naloxone dose. Additionally, the study showed that naloxone administered by intramuscular injection demonstrated greater bioavailability compared to naloxone administered intranasally using an improvised intranasal naloxone kit.

“This study was specifically designed to examine the impact of a common over-the-counter nasal medication on the absorption of naloxone,” said Eric Edwards, Vice President, Product Strategy at kaléo. “We’ve found that an over-the-counter nasal decongestant used for a common medical condition that affects the nasal passage, may impact the absorption of naloxone into the body when naloxone is administered intranasally using an improvised intranasal naloxone kit. These are important factors for a healthcare professional to consider when prescribing naloxone for take-home use as part of a patient’s opioid emergency plan.”

About the Studies

Poster #35: Comparative Simulated Use Study of a Novel Auto-Injector and Nasal Delivery Device for Naloxone Administration (poster viewing available September 7-9 with reception on September 8 from 6:30 p.m. – 8:30 p.m.; Level 3/Gracia 7)

The objective of this single-site, randomized, open-label study was to compare the usability of EVZIO and an improvised intranasal administration kit including the LMA MAD Nasal™ atomizer during a simulated opioid emergency. Participants 18-64 years of age (n=41) completed three study stages: use of both naloxone delivery devices (NDD) without training (review of instructions found on the devices was allowed), a 30-minute training with a registered nurse, including demonstration of correct use of each NDD, and use of the NDDs at least seven days post-training relying solely on memory from the training previously received. The primary endpoint was successful administration of a clinically meaningful naloxone dose into a mannequin without committing a critical task error that would prevent a clinically meaningful dose of naloxone from being delivered. Secondary endpoints from the study included the use of EVZIO or intranasal naloxone according to the instructions-for-use, use errors, time to completion of naloxone administration and participant preferences.

Poster #65: Pharmacokinetics of 2.0 mg Intranasal and Intramuscular Naloxone HCl Administration and the Impact of Vasoconstrictor Use on the Bioavailability of Intranasal Naloxone HCl (poster viewing available September 7-9 with reception on September 8 from 6:30 p.m. – 8:30 p.m.; Level 3/Gracia 7)

This randomized, open-label, single-dose, 3-period crossover pharmacokinetic study included men and women 18-55 years of age (n=36) diagnosed with chronic rhinitis, but with no clinically significant nasal abnormalities, surgery, polyps, trauma or other clinically significant abnormal nasal findings. The three study treatments included intramuscular administration of 2.0 mg naloxone (1 mg/mL in each thigh) using a standard syringe and needle (IM group), intranasal administration of 2.0 mg naloxone (1 mg/mL in each nostril) using the LMA MAD Nasal atomizer (IN group) and intranasal administration of 2.0 mg naloxone 30 minutes after intranasal administration of Afrin®, a commonly used over-the-counter nasal vasoconstrictor that contains oxymetazoline, (V+IN group). Blood samples for naloxone concentrations were collected pre-dose through 8-hours post-dose.

Pharmacokinetic analyses found that Cmax and total naloxone exposure was greatest in the IM group compared to the IN and V+IN groups. Median Tmax was 15 minutes for IM and IN groups and 20 minutes for V+IN group. During the early critical period of absorption, mean AUCpartial was greater for IN than V+IN.

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About Opioid-Induced Respiratory Depression (OIRD) and Overdose

Opioid emergencies, such as an accidental overdose, are a growing public health epidemic. On average, 79 people die from opioids, including prescription opioid analgesics and heroin, every day in the United States.[1], Approximately 136,000 opioid emergency department visits occur each year.[2] Many communities throughout the United States are facing a devastating heroin epidemic. Additionally, there are nearly two times the number of prescription opioid-related deaths as compared to heroin-related deaths.1 On average, 3,300 children five years old and younger suffer from unintentional opioid exposures and poisonings each year.[3]

Life-threatening opioid emergencies result in respiratory and/or central nervous system depression. Opioid-Induced Respiratory Depression (OIRD) is the most important serious adverse effect of opioids as it can be immediately life-threatening.[4] In addition to the risk of an opioid overdose associated with an opioid use disorder, there may be an increased risk of life-threatening OIRD even when patients take a prescribed dose of an opioid as directed. For example, taking high doses of opioids, taking an opioid in combination with other drugs (e.g., benzodiazepines) or alcohol, or if there is a history of certain medical conditions (e.g., COPD, severe asthma) places individuals at higher risk for life-threatening OIRD.[5],[6],[7] Seconds count when a life-threatening OIRD event occurs. Without rapid intervention, brain injury or death can occur in as little as 4 minutes.[8] Most life-threatening OIRD emergencies occur in the home and are witnessed by family and friends who may be in the best position to intervene quickly.[9]

Naloxone is an opioid antagonist that displaces opioids from the receptors in the brain, temporarily reversing the life-threatening breathing problems that can occur during an opioid emergency.[10]

About EVZIO (EVV-zee-oh)

EVZIO (naloxone HCl injection) Auto-injector is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. EVZIO is intended for immediate administration as emergency therapy in settings where opioids may be present. EVZIO is not a substitute for emergency medical care. EVZIO is an intelligent auto-injection system that provides simple, on-the-spot voice and visual guidance. EVZIO is small, easy-to-carry and easy-to-use to help patients and caregivers keep it on hand so they can take fast, confident action administering EVZIO during an opioid emergency.[11] Each EVZIO pre-filled, single-use, hand-held Auto-injector delivers a single 0.4 mg dose of naloxone. Each EVZIO prescription comes with two Auto-injectors and a Trainer. For more information on EVZIO, including full Prescribing Information, visit www.EVZIO.com.

EVZIO IMPORTANT SAFETY INFORMATION

EVZIO is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the ingredients in EVZIO.

The following warnings and precautions should be taken when administering EVZIO:

  • Due to the duration of action, keep the patient under continued surveillance and repeated doses of naloxone should be administered, as necessary, while awaiting emergency medical assistance.
  • Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance.
  • Reversal of respiratory depression by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete.
  • Use in patients who are opioid dependent may precipitate acute abstinence syndrome.
  • Patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects should be monitored in an appropriate healthcare setting.
  • In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated.

The following adverse reactions have been identified during use of naloxone hydrochloride in the postoperative setting: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in postoperative patients have resulted in significant reversal of analgesia and have caused agitation.

Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated signs and symptoms of opioid withdrawal including: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, and tachycardia. In the neonate, opioid withdrawal signs and symptoms also included: convulsions, excessive crying, and hyperactive reflexes.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. For full Prescribing Information visit http://evzio.com/pdfs/Evzio PI.PDF.

About kaléo (kuh-LAY-oh)

Kaléo is a pharmaceutical company dedicated to building innovative solutions for serious and life-threatening medical conditions. Our mission is to provide innovative solutions that empower patients to confidently take control of their medical conditions. We believe patients and caregivers are the experts on how their medical condition impacts their lives, and are an integral part of our product development process. Each kaléo product combines an established drug with an innovative delivery platform with the goal of achieving superiority and cost effectiveness. Kaléo is a privately-held company headquartered in Richmond, Virginia. For more information, visit kaleopharma.com.

About PAINWeek

PAINWeek is the largest US pain conference for frontline practitioners with an interest in pain management. Convening at The Cosmopolitan of Las Vegas for its 10th year on September 6-10, 2016, PAINWeek expects to welcome over 2,100 physicians, nurses, pharmacists and other healthcare professionals for a comprehensive program of course offerings, satellite events and exhibits. Over 120 hours of continuing medical education activities will be presented. To learn more and register for PAINWeek 2016, visit www.painweek.org.

Media Contact:
Mark Herzog
kaléo
mark.herzog@kaleopharma.com
804-545-6360 ext. 318 (office)

[1] Rudd RA, Aleshire N, Zibbell JE, Gladden M. Increase in Drug and Opioid Overdose Deaths – United States, 2000-2014. MMWR 2015;64(50-51):1378-82
[2] Yokell et al. Presentation of Prescription and Nonprescription Opioid Overdoses to US Emergency Departments. JAMA Int. Med. 2014; 174(12):2034-7.
[4] Food and Drug Administration. FDA Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics, 2014.
[5] Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients. Pain Med. 2014; 15:1911-1929.
[6] Bohnert A, Valenstein M, Bair MJ, et al. Association between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths. 2011; 305(13):1315-1321.
[7] Gudin JA, Mogali S, Jones JD, Comer SD. Risks, Management, and Monitoring of Combination Opioid, Benzodiazepines, and/or Alcohol Use. Postgrad Med J. 2013; 125(4):115-130.
[8] Caplan LR, Hurst JW, Chimowitz MI. Cardiac arrest and other hypoxic-ischemic insults. In: Clinical Neurocardiology. New York, NY: CRC Press; 1999.
[9] World Health Organization. Community Management of Opioid Overdose. Geneva, Switzerland: WHO, 2014.
[10] Straus M, Ghitza U, Tai B. Preventing deaths from rising opioid overdose in the US – the promise of naloxone antidote in community-based naloxone take-home programs. Subst Abuse Rehabil. 2013:65-72.
[11] Evans, E et al. Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. Pain Ther. 2015 Jun; 4(1): 89–105.