A Pharmacokinetic Study of the Coadministration of LY2216684 With Sertraline
This study has been completed.
Information provided by:
Eli Lilly and Company
First received: November 29, 2010
Last updated: January 27, 2011
Last verified: January 2011
LY2216684 is being studied as adjunctive treatment for MDD in patients who are partial responders to SSRIs. Sertraline is a medication that is widely used to treat MDD and it is a known substrate of CYP450s, including CYP2D6, CYP2C19 and CYP3A4, and a modest inhibitor of CYP2D6. Based on the diversity of hepatic metabolic clearance pathways for LY2216684 and its elimination by the kidney, it is expected that CYP2D6 inhibition by sertraline will not result in a substantial change in the PK profile of LY2216684. LY2216684 is only known to be a moderate inhibitor of CYP2C19 so it is unlikely that coadministration of sertraline with LY2216684 will result in a clinically meaningful change in the PK of sertraline. This study is being conducted to test these hypotheses.
Major Depressive Disorder
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||LY2216684 and Sertraline Pharmacokinetic Interaction Study in Healthy Subjects
Primary Outcome Measures:
- Pharmacokinetics, concentration maximum (Cmax) of LY2216684 [ Time Frame: Day 3, day 13 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics, time to concentration maximum (tmax) of LY2216684 [ Time Frame: Day 3, day 13 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics, area under the concentration curve (AUC) of LY2216684 [ Time Frame: Day 3, day 13 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics, concentration maximum (Cmax) of sertraline [ Time Frame: Day 10, day 13 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics, time to concentration maximum (tmax) of sertraline [ Time Frame: Day 10, day 13 ] [ Designated as safety issue: Yes ]
- Pharmacokinetics, area under the concentration curve (AUC) of sertraline [ Time Frame: Day 10, day 13 ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||December 2010 (Final data collection date for primary outcome measure)
Period 1: 18 mg oral dose of LY2216684 on days 1-3
Period 2: 50 mg oral dose of sertraline on day 4, followed by 100 mg oral dose of sertraline on days 5 to 10
Period 3: 18 mg oral dose of LY2216684 and 100 mg oral dose of sertraline on days 11-13
|Ages Eligible for Study:
||18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Are overtly healthy as determined by medical history and physical examination.
- Male subjects - Agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug.
- Female subjects - Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control for 6 weeks prior to administration of study drug, and agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or Women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone [FSH] level greater than or equal to 40 mIU/mL).
- Are between the body mass index of up to 32.0 kg/m2, inclusive.
- Have screening clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.
- Have venous access sufficient to allow blood sampling as per the protocol.
- Have normal blood pressure and pulse rate (supine position and standing) as determined 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 institutional review board (IRB) governing the site.
- Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device other than the study drug used in this study, 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/intolerance to LY2216684, sertraline, or related compounds.
- Are persons who have previously completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to screening.
- Have a clinically significant abnormality in the 12-lead ECG as determined by the investigator.
- Have significant history of or current cardiovascular (including dysrhythmias), respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
- Have a history of seizure disorders.
- Have a history or presence of the signs and/or symptoms of hyponatremia.
- Have a history or presence of the signs and/or symptoms of hyperthyroidism as determined by an abnormal thyroid stimulating hormone (TSH) at screening.
- Have a history or presence of the signs and/or symptoms of urinary retention or benign prostatic hypertrophy.
- Show evidence of significant active neuropsychiatric disease or a history of suicidal thoughts or suicide attempt.
- Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
- Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
- Show evidence of hepatitis C and/or positive hepatitis C antibody.
- Show evidence of hepatitis B and/or positive hepatitis B surface antigen.
- Are women with a positive pregnancy test or women who are lactating.
- Intend to use over-the-counter or prescription medication within 14 days prior to dosing unless deemed acceptable by the investigator and sponsor's medical monitor
- Have donated blood of more than 500 mL within 4 weeks prior to screening.
- Have an average weekly alcohol intake that exceeds 14 units per week or are unwilling to stop alcohol consumption 48 hours prior to Check-in until the completion of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
- Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any subjects unwilling to adhere to study caffeine restrictions.
- Have used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment.
- Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study.
- Have a documented or suspected history of glaucoma.
- Subjects determined to be unsuitable by the investigator for any reason.
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01250873
|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.
|Daytona Beach, Florida, United States |
Eli Lilly and Company
||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
||Chief Medical Officer, Eli Lilly
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 29, 2010
||January 27, 2011
||United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 27, 2016
Depressive Disorder, Major
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Serotonin Uptake Inhibitors