A Study to Evaluate the Effect of Genotype on LY2216684

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01460381
First received: October 24, 2011
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

The study will evaluate how genetic profiles respond to LY2216684 and the effect of Quinidine on the pharmacokinetics (PK) of LY2216684 in a specific genetic profile. Side effects will be documented.


Condition Intervention Phase
Depressive Disorder, Major
Drug: LY2216684
Drug: Quinidine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Investigate the Effect of CYP2C19 Phenotype on the Pharmacokinetics of LY2216684 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics: Area under the plasma concentration-time curve from time 0 to infinity [AUC(0-∞)] of LY2216684 in cytochrome P450 (CYP)2C19 extensive metabolizers (EM) versus poor metabolizers (PM) [ Time Frame: Predose up to 120 hours post administration of study drug ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum observed plasma concentration (Cmax) of LY2216684 in cytochrome P450 (CYP)2C19 extensive metabolizers (EM) versus poor metabolizers (PM) [ Time Frame: Predose up to 120 hours post administration of study drug ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time to maximum observed plasma concentration (tmax) in cytochrome P450 (CYP)2C19 extensive metabolizers (EM) versus poor metabolizers (PM) [ Time Frame: Predose up to 120 hours post administration of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area under the plasma concentration-time curve from time 0 to infinity [(AUC(0-∞)] of LY2216684 + Quinidine in cytochrome P450 (CYP)2C19 poor metabolizers (PM) [ Time Frame: Predose up to 120 hours post administration of Quinidine ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum observed plasma concentration (Cmax) of LY2216684 + Quinidine in CYP2C19 poor metabolizers [ Time Frame: Predose up to 120 hours post administration of Quinidine ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time to maximum observed plasma concentration (tmax)in CYP2C19 poor metabolizers [ Time Frame: Predose up to 120 hours post administration of Quinidine ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: October 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2216684 + Quinidine
In Period 1 (Day -1 up to Day 6), a single 18 mg oral dose of LY2216684 will be administered on Day 1 for CYP2C19 poor metabolizers (PM). In Period 2 (Day 7 up to Day 16), a 300 mg oral dose of quinidine sulfate controlled release (CR) will be administered once daily (QD) on Days 8 through 15 and a single 18 mg oral dose of LY2216684 will be administered on Day 11.
Drug: LY2216684
Administered orally
Drug: Quinidine
Administered orally
Experimental: LY2216684
In Period 1, a single 18 mg oral dose of LY2216684 will be administered on Day 1 for CYP2C19 extensive metabolizers (EM) participants. EM participants do not participate in Period 2.
Drug: LY2216684
Administered orally

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Are overtly healthy males or females, as determined by medical history and physical examination
  • Male participants: Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug
  • Female participants: Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control (not including hormonal contraceptives) for 4 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 the study drug or; Are women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone [FSH] level >40 mIU/mL)
  • Have a body weight >50 kg
  • Have 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 for blood sampling as per the protocol
  • 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
  • Have normal blood pressure (BP) and pulse rate (PR) (sitting position) as determined by the investigator
  • Are predicted to have cytochrome P450 (CYP)2C19 extensive metabolizer (EM) or poor metabolizer (PM) phenotypes as determined by genotyping assessment
  • Are predicted to have CYP2D6 EM phenotype as determined by genotyping assessment.

Exclusion Criteria:

  • Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product; 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 or quinidine, related compounds, or any components of the formulation
  • Are persons who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to Screening.
  • Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
  • Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation
  • Have a history of or current cardiovascular, 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
  • Regularly use known drugs of abuse and/or show positive findings on urinary drug screening
  • Show evidence of human immunodeficiency virus (HIV) infection 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 or during the study unless deemed acceptable by the investigator and Sponsor's medical monitor. Exceptions include influenza vaccinations, the use of topical medication (provided there is no evidence of chronic dosing with the risk of systemic exposure), occasional use of acetaminophen/paracetamol/ibuprofen, and hormone replacement therapy including thyroid replacement (stable dose for at least 1 month).
  • Have donated blood of more than 500 mL within the last month
  • Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to stop alcohol consumption 48 hours prior to dosing in Period 1 until Discharge (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)
  • In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study
  • Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any participants unwilling to stop caffeine consumption from 48 hours prior to dosing in Period 1 until Discharge
  • Have consumed grapefruit or grapefruit-containing products 30 days prior to enrollment or unwilling to abstain during the study
  • Have a documented or suspected history of glaucoma
  • Participants unwilling to adhere to the smoking restrictions of the Clinical Research Unit (CRU) while a resident of the CRU
  • Use of known inhibitors and/or inducers of CYP2C19 and CYP2D6 (with the exception of quinidine per protocol) 30 days prior to enrollment or are unwilling to avoid them during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01460381

Locations
United States, Texas
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.
Dallas, Texas, United States
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

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01460381     History of Changes
Other Study ID Numbers: 14397, H9P-EW-LNDZ
Study First Received: October 24, 2011
Last Updated: November 1, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Quinidine
Quinidine gluconate
Adrenergic Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Anti-Arrhythmia Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Cardiovascular Agents
Cholinergic Agents
Cholinergic Antagonists
Enzyme Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 30, 2014