A Study of LY2216684 and Theophylline in Healthy Subjects

NCT01263106 | Completed Phase 1 Results

• 2 other identifiers: 12594H9P-EW-LNCE
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to confirm that LY2216684 is not an inhibitor of cytochrome P450 1A2 (CYP1A2) in healthy participants using theophylline as a probe substrate for the enzyme. Because LY2216684 has been observed to increase heart rate in some healthy participants, this study will also assess heart rate when coadministered with theophylline.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (3)

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

  The Least Squares (LS) geometric mean was based on AUC0-∞. The AUC for theophylline was calculated on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.

  Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Theophylline

  The Least Squares (LS) geometric mean was based on Cmax for theophylline on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.

  Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3

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

  This outcome was measured based on Tmax for theophylline on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.

  Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3

Secondary Outcomes (2)

• Mean Change From Baseline in Heart Rate: 200 mg Theophylline

  Baseline, Day 1

• Mean Change From Baseline in Heart Rate: 18 mg LY221684 + 200 mg Theophylline

  Baseline, Day 1, Day 3

Study Arms (2)

Theophylline, LY2216684 + Theophylline

EXPERIMENTAL

Period 1: single 200-milligram (mg) theophylline oral dose on Day 1; Washout period of at least 7 days; Period 2: 18 mg LY2216684 orally, once daily on Days 1-5 with single 200-mg theophylline oral dose coadministered on Day 3

Drug: LY2216684; Drug: Theophylline

LY2216684 + Theophylline, Theophylline

EXPERIMENTAL

Period 1: 18 mg LY2216684 orally, once daily on Days 1-5 with single 200-mg theophylline oral dose coadministered on Day 3; Washout period of at least 7 days; Period 2: single 200-mg theophylline oral dose on Day 1

Drug: LY2216684; Drug: Theophylline

Interventions

LY2216684 DRUG

18-mg LY2216684 oral dose

LY2216684 + Theophylline, Theophylline; Theophylline, LY2216684 + Theophylline

Theophylline DRUG

200-mg theophylline oral dose

LY2216684 + Theophylline, Theophylline; Theophylline, LY2216684 + Theophylline

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 for 6 weeks prior to administration of study drug and agree to use a reliable method of birth control both during the study and for 1 month following the last dose of study drug; or are women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone \[FSH\] \>40 mass International Units per milliliter \[mIU/mL\]).
• Have 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 blood sampling as per the protocol.
• Have normal sitting blood pressure and pulse rate as determined by the investigator.
• Are reliable and willing to be 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 (ERB) governing the site.

You may not qualify if:

• 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.
• 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, 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 LY2216684, theophylline, 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 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.
• 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.
• Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of cytochrome P450 1A2 (CYP1A2) within 30 days prior to dosing.
• 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.

Dallas, Texas, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

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

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: December 20, 2010
• Study Start: December 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: July 8, 2019
• Results First Posted: July 8, 2019

Record last verified: 2019-04

Locations

US (1)