US 2010.0196286A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0196286 A1 ARMER et al. (43) Pub. Date: Aug. 5, 2010 (54) INHALATION DELIVERY METHODS AND A6II 3/54 (2006.01) DEVICES A63L/433 (2006.01) A6IR 9/12 (2006.01) (76) Inventors: Thomas A. ARMER, Cupertino, A 6LX 3/557 (2006.01) CA (US); Robert O. Cook, A 6LX 3/553 (2006.01) Hillsborough, NJ (US); Terry A 6LX 3/59 (2006.01) Alfredson, San Mateo, CA (US); A 6LX 3L/21995 (2006.01) Anthony Sun, New York, NY (US) A6II 3/343 (2006.01) A63L/404 (2006.01) Correspondence Address: A6II 3/472 (2006.01) MORRISON & FOERSTER LLP A 6LX 3/553 (2006.01) 7SS PAGE MILL RD A63L/506 (2006.01) PALO ALTO, CA 94304-1018 (US) A6IP 25/22 (2006.01) A6IP 25/24 (2006.01) (22) Filed: Dec. 1, 2009 (52) U.S. Cl. ........... 424/45: 514/396; 514/401; 514/617; 514/632: 514/183: 514/227.2: 514/362; 514/220; Related U.S. Application Data 514/221; 514/259.31; 514/249; 514/468; (60) Provisional application No. 61/119,015, filed on Dec. 514/419:514/307: 514/211.13: 514/252.15 1, 2008. (57) ABSTRACT Publication Classification Methods, devices and kits for treating sleep disorders, anxiety (51) Int. Cl. disorders, and developmental disorders, and/or for inducing A 6LX 3L/395 (2006.01) an arousable state of sedation in a Subject, are described. For A6 IK 3/4164 (2006.01) example, inhalation methods, devices and kits for treating A6 IK 3/468 (2006.01) insomnia, anxiety and/or ADHD using one or more C2-adr A6 IK3I/I65 (2006.01) energic agonists such as dexmedetomidine or clonidine are A6 IK3I/55 (2006.01) described. US 2010/0196286 A1 Aug. 5, 2010 NHALATION DELVERY METHODS AND the counter and does not seem to induce dependence, but its DEVICES effectiveness may decrease over time. Additionally, it may result in next-day sedation. CROSS-REFERENCE TO RELATED 0006. One specific form of insomnia is middle-of-the APPLICATIONS night insomnia (or “MOTN insomnia'). People suffering 0001. This application claims the benefit of U.S. Provi from MOTN insomnia experience difficulty returning to sional Application No. 61/119,015, filed Dec. 1, 2008, the sleep after awakening in the middle of their normal sleep disclosure of which is herein incorporated by reference in its period (which, it should be noted, may not necessarily be at entirety. night (e.g., as in the case of a shift worker)). While they may not have problems initially falling asleep, they wake up prior FIELD to their intended wake time. Because it disrupts normal sleep patterns, MOTN insomnia can result in fatigue following the 0002 Methods and devices for treating sleep disorders, normal sleep period. One or more of the above treatments anxiety disorders, and/or developmental disorders, and/or for may be unsuitable for treating MOTN insomnia. For inducing an arousable state of sedation in a subject (e.g., for example, the treatment or treatments may be slow to induce a perioperative, diagnostic, or non-Surgical procedure), are sleep and/or may require administration prior to about seven described herein. More specifically, inhalation methods and to nine hours in bed to avoid residual sleepiness after the devices for inducing an arousable state of sedation in a Sub normal wake-up time. Also, Some of the above-described ject, and/or for treating insomnia (e.g., MOTN insomnia), hypnotics may be administered prophylactically, which may anxiety, and/or attention deficit disorders (e.g., Attention result in unnecessary medication and/or overmedication. Deficit Hyperactivity Disorder, or ADHD) using one or more Moreover, it may be undesirable to have to self-administer a C2-adrenergic agonists (e.g., dexmedetomidine, medetomi pill or injection in the middle of the night to treat insomnia. dine, clonidine, guanfacine, etc.) are described herein. 0007 Another common form of insomnia is sleep onset insomnia, which is estimated to afflict approximately 10% of BACKGROUND the population in the United States. A person suffering from 0003 Sleep disorders (e.g., insomnia), anxiety disorders sleep onset insomnia is not able to fall asleep upon retiring. (e.g., panic disorder), and developmental disorders (e.g., The sleepless person may be restless (often for hours) and/or Attention-Deficit Hyperactivity Disorder, or ADHD) affect anxious, and may experience mental processing of daily millions of people. For example, it is estimated that insomnia activities which exacerbates the insomnia. Sleep onset may affects about 60-70 million Americans. Sleep, anxiety, and be induced by taking one or more medications in advance of developmental disorders can have a significant negative retiring (e.g., one hour prior to retiring). However, this may impact on quality of life, compromising the health, general interfere with the person's evening schedule or routine. More well-being, and/or safety of the person suffering from the over, taking Such medications in advance of retiring has led to disorder. Attention deficit disorders, e.g., ADHD, affect both morbidity, particularly in the form of hip fractures from adults and children, lowering their quality of life and produc drowsiness-induced falls. tivity. In some instances, a person may suffer from more than 0008 Sleep maintenance insomnia is another form of one of these disorders. For example, a person may suffer from sleeplessness. In the case of sleep maintenance insomnia, the both a sleep disorder and an anxiety disorder (e.g., with one Subject has difficulty falling asleep and remaining asleep for disorder causing the other). a prolonged period of normal sleep cycles. This type of 0004 Insomnia involves a persistentinability to fall asleep insomnia leaves the Subject chronically fatigued and unable or persistent difficulty in falling asleep and/or remaining to restore normal sleep patterns. Many of the therapeutic asleep during normal sleep times. A persistentinability to fall agents used to treat sleep maintenance insomnia have long asleep is more specifically referred to as sleep onset insomnia, half-lives, and therefore have long duration of effect (e.g., while the inability to remain asleep is more specifically usually 5-6 or more hours of non-arousable sedation). Such referred to as sleep maintenance insomnia. Insomnia may be long duration of effect can result in a morning "hangover. transient (e.g., lasting for days to weeks), acute (e.g., lasting with associated reduction in cognitive ability during waking for several weeks to several months), or chronic (e.g., lasting hours. Moreover, the use of long-acting agents may result in for years). Insomnia may be caused by, for example, certain disrupted sleep quality (sleep cycle disruption), and may also drugs and/or stimulants (e.g., caffeine), hormonal fluctua cause sleep-walking, sleep-eating and/or sleep-driving. tions, stress, anxiety, depression, and/or neurological disor While some benzodiazepineagents with short half-lives may ders, among other factors. be used, they can precipitate withdrawal symptoms, in addi 0005 Insomnia may be treated using drugs in the form of tion to causing amnesia and/or habitualization. In view of the pills, capsules, fast-melt tablets or injections. For example, above, it would be desirable to provide a rapidly-acting agent sedative hypnotic drugs such as benzodiazepines have been that does not have a prolonged duration of effect, and that has used to treatinsomnia for many years. Examples of benzodi minimal adverse side effects. It would be particularly desir azepines include temazepam (e.g., Restoril(R), flunitrazepam able to provide a rapidly-acting sleep maintenance agent that (e.g., Rohypnol (R), triazolam (e.g., Halcion.R.), flurazepam has minimal or no adverse effect on sleep cycle, and that does (e.g., Dalmane(R), nitrazepam (e.g., Mogadon(R), and mida not provide a waking hour sedative hangover. Zolam (e.g., Versed R). Non-benzodiazepine agents also have 0009 Anxiety disorders are psychological and/or physi been used to treat insomnia and include, for example, Zolpi ological disorders that may result in a person experiencing dem (e.g., Ambien R and Ambien CRR), Zaleplon (e.g., anger, fear, apprehension, and/or worry. Anxiety may result in Sonata(R), and eSZopiclone (e.g., Lunesta(R). In some cases, physical effects, such as heart palpitations, nausea, chest pain, the antihistamine diphenhydramine (e.g., Benadryl R) has shortness of breath, stomachaches, headaches, Sweating, been used as a sleep aid. Diphenhydramine is available over trembling, diarrhea, chills, pupillary dilation, hot flashes, US 2010/0196286 A1 Aug. 5, 2010 Sudden tiredness, hypertension, and/or digestion problems. acting medication that could induce sleep or sedation within There are many different types of anxiety disorders, including about 30 minutes or less of administration may avoid the generalized anxiety disorder, panic disorder, phobias Such as schedule limitations of current remedies, while minimizing agoraphobia, Social anxiety disorder, obsessive-compulsive the potential for drowsiness-induced injury. Such medication disorder, post-traumatic stress disorder, and separation anxi could be taken immediately before or after the person has ety disorder. An additional form of anxiety is hospital proce retired for the night, thus assuring that the person is already in dural anxiety, such as that experienced by a patient prior to a bed when the sedation takes effect. procedure (e.g., needle use, magnetic resonance imaging 0014. It would also be desirable to be able to induce an (MRI) scanning, etc.). Some anxiety sufferers experience arousable state of sedation in a Subject (e.g., for a periopera panic attacks, which usually come with little or no warning. A tive, diagnostic and/or non-Surgical procedure). A method of person experiencing a panic attack may suffer from head inhaled sedation can be especially useful prior to Surgical aches, heart palpitations, dizziness, insomnia and/or chest procedures for pediatric patients.