A Study to Evaluate the Effect of Clarithromycin on LY2216684

NCT01460407 | Completed Phase 1 Results

• 2 other identifiers: 14401H9P-EW-LNEB
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate the effect of Clarithromycin on the pharmacokinetics (PK) of LY2216684 in healthy participants. Side effects will be documented. There will be 2 study periods (5 and 9 days) and follow up will occur at least 7 days after the last dose. Screening is required within 45 days prior to the start of the study.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-∞) of LY2216684

  AUC0-∞ of LY2216684 was calculated during Period 1, when 18-mg LY2216684 was administered alone and Period 2, when Clarithromycin was coadministered with LY2216684. The outcome was presented as geometric Least Squares (LS) mean and the 90% Confidence Interval (CI). Geometric LS mean was controlled by participant and treatment.

  Predose up to 96 hours post administration of LY2216684 (Day 1) and LY2216684 + Clarithromycin (Day 10)

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2216684

  Cmax of LY2216684 was calculated during Period 1, when 18-mg LY2216684 was administered alone, and Period 2, when Clarithromycin was coadministered with LY2216684. The outcome was presented as geometric LS mean and the 90% CI. Geometric LS mean was controlled by participant and treatment.

  Predose up to 96 hours post administration of LY2216684 (Day 1) and LY2216684 + Clarithromycin (Day 10)

• Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of LY2216684

  Tmax of LY2216684 was calculated during Period 1, when 18-mg LY2216684 was administered alone, and Period 2, when Clarithromycin was coadministered with LY2216684. The outcome was presented as geometric LS mean and the 90% CI. Geometric LS mean was controlled by participant and treatment.

  Predose up to 96 hours post administration of LY2216684 (Day 1) and LY2216684 + Clarithromycin (Day 10)

Study Arms (1)

LY2216684 + Clarithromycin

EXPERIMENTAL

Participants will receive a single 18-mg oral dose of LY2216684 on Days 1 and 10. Clarithromycin (500 mg) will be administered twice a day (BID) on Days 6 through 13.

Drug: LY2216684; Drug: Clarithromycin

Interventions

LY2216684 DRUG

Administered orally

LY2216684 + Clarithromycin

Clarithromycin DRUG

Administered orally

LY2216684 + Clarithromycin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are overtly healthy as determined by medical history and physical examination
• Male participants:
• o 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:
• o 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 study drug; or women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion) or menopause \[at least 1 year without menses or 6 months without menses and a follicle stimulating hormone (FSH) \>40 milli-international units per milliliter (mIU/mL)\]
• Have a body weight \>50 kilograms (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 both cytochrome P450 (CYP)2D6 and CYP2C19 extensive metabolizer (EM) phenotypes as determined by genotyping assessment

You may not qualify if:

• 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 clarithromycin, 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 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
• Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation
• Have a documented or suspected history of glaucoma
• 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 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, hormone replacement therapy including thyroid replacement (stable dose for at least 1 month)
• Use of known inhibitors and/or inducers of CY2D6, CYP2C19, and/or CYP3A 30 days prior to enrollment or are unwilling to avoid them during the study (except for use of clarithromycin)
• Have donated blood of more than 500 mL within the last month

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

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, 32117, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol; Clarithromycin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2011
• First Posted: October 26, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 19, 2018
• Results First Posted: October 19, 2018

Record last verified: 2018-03

Locations

US (1)