A Bioequivalence (BE) Study in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT01177943
• Recruitment Status: Completed
• First Posted: August 9, 2010
• Results First Posted: October 27, 2011
• Last Update Posted: October 27, 2011
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: Atomoxetine	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LY139603 Bioequivalence Study Comparing Atomoxetine Oral Solution and Capsule Formulation in Healthy Adult Male Japanese Subjects
• Study Start Date: August 2010
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atomoxetine Oral Solution	Drug: Atomoxetine; Administered orally, once.; Other Names: LY139603; Strattera
Active Comparator: Atomoxetine Capsule Formulation	Drug: Atomoxetine; Administered orally, once.; Other Names: LY139603; Strattera

Outcome Measures

Primary Outcome Measures :

1. Maximum Observed Plasma Concentration (Cmax) [ 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 ]
   The Cmax values are based on the atomoxetine plasma concentration. The Least Squares (LS) Mean Value was based on treatment, period, group, and subject.
2. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)] [ 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Japan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Fukuoka, Japan, 810-0064

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01177943
• Other Study ID Numbers: 13554; B4Z-JE-LYEO ( Other Identifier: Eli Lilly and Company )
• First Posted: August 9, 2010
• Results First Posted: October 27, 2011
• Last Update Posted: October 27, 2011
• Last Verified: September 2011

Additional relevant MeSH terms:

Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Atomoxetine Hydrochloride; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs