Table 1.

Key Inclusion and Exclusion Criteria

Key Inclusion Criteria	Key Exclusion Criteria
Healthy male and female (trial B) adults ≤55 years old with normal blood pressure, pulse, and respiration	History of seizures, epilepsy, or recognized increase risk of seizure
Tolerance to cold-induced pain of ≥20 and ≤120 seconds	History of cirrhosis or laboratory evidence of liver disease
Negative urine for substances of abuse	Known or suspected alcohol or drug abuse within the past 6 months
Normal or intermediate CYP2D6 metabolizer (trial B)	Inhibitors of monoamine oxidase, serotonin and/or norepinephrine reuptake, and other medications or supplements known to induce or inhibit drug metabolism or that may affect the serotonergic neurotransmitter system
Adequate hematologic and liver function per predefined limits	Ethanol, grapefruit, grapefruit-related citrus fruits (eg, Seville oranges, pomelos), grapefruit-related juices or other new medication
Cockcroft-Gault glomerular filtration rate of ≥60 mL/min and urinalysis with ≤+1 glucose, +1 ketones, and +1 protein	Pregnant or breast feeding (trial B)
Body mass index of 18.0–32 kg/m2
If female of childbearing potential, must use adequate contraception
Electrocardiogram without clinically significant changes
Negative serology for HIV, hepatitis B surface antigen, and hepatitis C virus antibody