A Study of the Effect of LY2216684 on Lorazepam

NCT01275144 | Completed Phase 1 Results

• 2 other identifiers: 12596H9P-EW-LNCG
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how much lorazepam gets into the blood and how long it takes the body to get rid of it when given together with LY2216684. Information about any side effects that may occur will also be collected.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics of Lorazepam, Maximum Plasma Concentration (Cmax)

  The geometric least squares mean and 90% Confidence Interval are presented. Geometric least squares mean corrected for participant, treatment and random error.

  Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose

• Pharmacokinetics of Lorazepam, Time to Maximum Plasma Concentration (Tmax)

  Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose

• Pharmacokinetics of Lorazepam, Area Under the Plasma Concentration Curve (AUC) From Time 0 to Infinity (∞)

  The geometric least squares mean and 90% Confidence Interval are presented. Geometric least squares mean corrected for participant, treatment and random error.

  Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose

Secondary Outcomes (21)

• Change From Baseline in Cognitive Function-Simple Reaction Time

  Baseline, 2, 4, 8 hours on Day 3

• Change From Baseline in Cognitive Function-Digit Vigilance Targets Detected

  Baseline, 2, 4, 8 hours on Day 3

• Change From Baseline in Cognitive Function-Digit Vigilance Speed

  Baseline, 2, 4, 8 hours on Day 3

• Change From Baseline in Cognitive Function-Digit False Alarms

  Baseline, 2, 4, 8 hours on Day 3

• Change From Baseline in Cognitive Function-Choice Reaction Time

  Baseline, 2, 4, 8 hours on Day 3

Study Arms (2)

LY2216684+lorazepam, placebo+lorazepam

EXPERIMENTAL

Oral 18 mg doses of LY2216684 on days 1-6 with a single oral 1 mg dose of lorazepam on day 3 in treatment period 1. Oral doses of placebo on days 1-6 with a single oral 1 mg dose of lorazepam on day 3 in treatment period 2. There is a washout period of at least 7 days between dosing periods.

Drug: LY2216684; Drug: Placebo; Drug: Lorazepam

Placebo+Lorazepam, LY2216684+Lorazepam

EXPERIMENTAL

Oral doses of placebo on days 1-6 with a single oral 1 mg dose of lorazepam on day 3 in treatment period 1. Oral 18 mg doses of LY2216684 on days 1-6 with a single oral 1 mg dose of lorazepam on day 3 in treatment period 2. There is a washout period of at least 7 days between dosing periods.

Drug: LY2216684; Drug: Placebo; Drug: Lorazepam

Interventions

LY2216684 DRUG

Administered orally

LY2216684+lorazepam, placebo+lorazepam; Placebo+Lorazepam, LY2216684+Lorazepam

Placebo DRUG

Administered orally

LY2216684+lorazepam, placebo+lorazepam; Placebo+Lorazepam, LY2216684+Lorazepam

Lorazepam DRUG

Administered orally

LY2216684+lorazepam, placebo+lorazepam; Placebo+Lorazepam, LY2216684+Lorazepam

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 - 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 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 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 milli-international Units per milliliter \[mIU/mL\]).
• Have a body weight \>50 kilogram (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 (potassium, magnesium, and calcium values must be within the normal range).
• Have venous access sufficient to allow blood sampling as per the protocol.
• Have normal blood pressure and pulse rate (sitting position) 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 ethical review board (ERB) governing the site.

You may not qualify if:

• 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, lorazepam, benzodiazepines, 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 (including hormonal contraceptives) within 14 days prior to dosing unless deemed acceptable by the investigator and Sponsor's medical monitor, except for influenza vaccinations.
• Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of Uridine 5'-diphospho -glucuronosyltransferase (UGT) within 30 days prior to dosing.
• Have donated blood of more than 500 mL within the last month.
• Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption 48 hours prior to each study period and while resident at the clinical research unit (CRU) (1 unit = 12 ounces (oz) or 360 millimeters (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

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

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2011
• First Posted: January 12, 2011
• Study Start: December 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: March 11, 2019
• Results First Posted: March 11, 2019

Record last verified: 2018-11

Locations

GB (1)