An Ascending Dose Study of the Dexmedetomidine Transdermal System in Healthy Subjects

Exclusion Criteria22

• A history or presence of drug or alcohol dependence (excluding caffeine and nicotine), including subjects who have ever been in a drug rehabilitation program based on medical history of the past 10 years.
• Clinically significant abnormalities as judged by the investigator or designee and determined by physical examination , medical history, 12-lead electrocardiogram, vital signs, laboratory values, including serum kidney and liver function tests.
• Supine heart rate less than 60 or greater than 100 bpm, systolic blood pressure (BP) less than 90 or greater than 140 mmHg, or diastolic BP less than 60 or greater than 90 mmHg, when measured after being supine for at least 5 minutes
• Presence and or significant history of postural hypotension (determined through examination by the investigator or designee), or history of severe dizziness or fainting on standing.
• Subjects with a history of seizures, asthma (except for childhood asthma which has been
• asymptomatic for greater than or equal to 10 years), or obstructive pulmonary disease.
• Presence or history of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including ulcers or gastrointestinal bleeding), endocrine, immunologic, dermatologic, neurologic, oncologic, psychiatric disease/disorder (including suicidal ideation and behavior, organic brain disorder, or seizure disorder), or any other condition, which, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
• Abnormality (for example, scar, tattoo) or unhealthy skin (for example, burns, wounds) at the application site, according to examination by the investigator at screening, admission to the clinic, or prior treatment period of the study.
• An existing chronic skin disease or history of skin disease at the application site within the 30 days prior to screening.
• Use of any prescription drug (except acceptable forms of birth control) within 14 days prior to study drug administration and throughout the study.
• Use of any prescription or non-prescription product containing any sympathomimetic amine (for example, pseudoephedrine, phenylephrine, and others commonly found in cold preparations) within 14 days prior to study drug administration and throughout the study.
• Use of any natural health products (except vitamin or mineral supplements) within 14 days prior to study drug administration and throughout the study, unless in the opinion of the investigator or designee, the product will not interfere with the study procedures or data integrity, or compromise the safety of the subject.
• Use of a non-prescription drug within 7 days prior to study drug administration; subjects who have taken over-the-counter medications, other than those described above, may still be entered into the study, if in the opinion of the investigator or designee, the medication received will not interfere with the study procedures or data integrity, or compromise the safety of the subject.
• Positive test result for drugs of abuse at screening or prior to study drug dosing (testing can be repeated at the discretion of the investigator).
• Positive alcohol test at screening or prior to study drug dosing.
• Female subjects who are currently pregnant or lactating or who are planning to become pregnant within 30 days of last study drug administration.
• History of allergy or hypersensitivity to dexmedetomidine or dexmedetomidine hydrochloride.
• Positive for hepatitis B, hepatitis C, or the human immunodeficiency virus (HIV).
• Donation of blood or loss of blood (greater than 100 mL) within 30 days prior to study drug administration.
• Subject has a personal responsibility or already confirmed appointment(s) or court date(s) that would in any way prevent him/her from meeting the time commitments and visits required by the study.
• Treatment with any investigational drug, device, or biologic within 30 days prior to study drug administration.
• A subject who, in the opinion of the investigator or designee, is considered unsuitable for study entry and/or is unlikely to comply with the study protocol for any reason.