Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
To demonstrate the bioequivalence of 12.5 milliliters (mL) of atomoxetine oral solution (4 milligrams per milliliter \[mg/mL\]) compared with 2 capsules of atomoxetine (25 mg per capsule) in healthy adult male Japanese subjects.
Interventions
DRUGAtomoxetine
Administered orally, once.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Are healthy Japanese males, as determined by medical history and physical examination * Have a body mass index (BMI) of greater than or equal to 17.6 and less than or equal to 26.4 kg/m2 at screening * Cytochrome P450 2D6 (CYP2D6) genotype is categorized as extensive metabolizers (EM) from the result of screening test. EM includes Intermediate Metabolizer (IM) and Ultrarapid Metabolizer (UM). * Have clinical laboratory test results within normal reference range for the population and investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * Have given written informed consent approved by Lilly and the ethical review board governing the site before any trial activities
Exclusion criteria
* Are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted. * Persons who are employed by the sponsor (that is, employees, temporary contract workers, or designees responsible for conducting the study). * Are currently enrolled in, or discontinued within the last 4 months from, a clinical trial involving an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * Have known allergies to atomoxetine (LY139603) or related compounds. * Are persons who have ever used atomoxetine, or previously participated in this study or any other study investigating atomoxetine and received the study drug. * An abnormality in the 12-lead ECG that in the opinion of the investigator increases the risk of participating in the study, such as a corrected QT (QTc) interval \>450 milliseconds (msec). * Subjects with a current or past history of clinically significant elevated blood pressure (Supine systolic blood pressure greater than or equal to 140 millimeters of mercury \[mmHg\] or Supine diastolic blood pressure greater than or equal to 90 mmHg) * Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or of interfering with the interpretation of data. * Regularly use known drugs of abuse, or show positive findings on urinary drug screening. * Have a positive result for Human Immunodeficiency Virus (HIV) test, or show evidence of possible infection. * Have a positive result for hepatitis B antigen test, or show evidence of possible infection. * Have a positive result for hepatitis C antibody test, or show evidence of possible infection. * Have a positive result for syphilis test, or show evidence of possible infection. * Use or intend to use over-the-counter or prescription medication 7 and 14 days, respectively prior to dosing. * Blood donation of more than 200 mL of blood and component blood donation within one month prior to dosing, or those who have donated more than 400 mL of blood within 3 month prior to dosing, or history of blood donation of more than 950 mL within the last 12 months. * Have an average weekly alcohol intake that exceeds 21 units per week or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 360 mL of beer; 150 mL of wine; 45 mL of distilled spirits). * Subjects with a history of seizure, excluding febrile convulsion in childhood. * Exposure to a monoamine oxidase inhibitor (MAOI) drug or herbal preparations with central nervous system effects such as St. John's Wort within the last 2 weeks prior to dosing. * Subjects who have a history or presence of narrow-angle glaucoma. * Have a history or presence of significant neuropsychiatric disease (for example, maniac-depressive illness, schizophrenia, or depression). * Currently smoke in excess of 10 cigarettes per day, or equivalent in tobacco or nicotine substitutes, or are unwilling to stop smoking for the duration specified in the protocol * Subjects determined by the investigator or the sponsor to be inadequate for inclusion in this study for any other reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 4, 6, 8, 12, 18, and 24 hours post dose | The Cmax values are based on the atomoxetine plasma concentration. The Least Squares (LS) Mean Value was based on treatment, period, group, and subject. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)] | Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 4, 6, 8, 12, 18, and 24 hours post dose | The AUC (0-tlast) is the area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (tlast) and is based on the atomoxetine plasma concentration. The Least Squares (LS) Mean Value was based on treatment, period, group, and subject. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine Oral Solution First, Then Capsule Formulation Participants received 50 mg of atomoxetine orally (po), once (12.5 mL at 4 mg/mL). Participants received 2 capsules of atomoxetine (25 mg/capsule po), once. | 21 |
| Atomoxetine Capsule Followed by Oral Solution Participants received 2 capsules of atomoxetine (25 mg/capsule po), once. Participants received 50 mg of atomoxetine po, once (12.5 mL at 4 mg/mL). | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Atomoxetine Oral Solution First, Then Capsule Formulation | Atomoxetine Capsule Followed by Oral Solution | Total |
|---|---|---|---|
| Age Continuous | 23.0 years STANDARD_DEVIATION 4.4 | 23.4 years STANDARD_DEVIATION 2.9 | 23.2 years STANDARD_DEVIATION 3.7 |
| Race/Ethnicity, Customized Japanese | 21 participants | 21 participants | 42 participants |
| Region of Enrollment Japan | 21 participants | 21 participants | 42 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 21 Participants | 21 Participants | 42 Participants |
| weight (kg) | 62.29 kilograms (kg) STANDARD_DEVIATION 7.29 | 61.28 kilograms (kg) STANDARD_DEVIATION 5.9 | 61.79 kilograms (kg) STANDARD_DEVIATION 6.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 42 | 6 / 40 |
| serious Total, serious adverse events | 0 / 42 | 0 / 40 |
Outcome results
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)]
The AUC (0-tlast) is the area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (tlast) and is based on the atomoxetine plasma concentration. The Least Squares (LS) Mean Value was based on treatment, period, group, and subject.
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 4, 6, 8, 12, 18, and 24 hours post dose
Population: All participants who had an AUC value were included in the AUC analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Atomoxetine Oral Solution | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)] | 2220 nanogram hour per milliliter (ng*h/mL) |
| Atomoxetine Capsule Formulation | Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)] | 2150 nanogram hour per milliliter (ng*h/mL) |
90% CI: [1, 1.07]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax)
The Cmax values are based on the atomoxetine plasma concentration. The Least Squares (LS) Mean Value was based on treatment, period, group, and subject.
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 4, 6, 8, 12, 18, and 24 hours post dose
Population: All participants who had a Cmax value were included in the Cmax analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Atomoxetine Oral Solution | Maximum Observed Plasma Concentration (Cmax) | 456 nanogram per millileter (ng/mL) |
| Atomoxetine Capsule Formulation | Maximum Observed Plasma Concentration (Cmax) | 483 nanogram per millileter (ng/mL) |
90% CI: [0.858, 1.04]ANOVA