Major Depressive DisorderPhase 1NCT01275144
A Study of the Effect of LY2216684 on Lorazepam
A Phase 1 study testing LY2216684 and Lorazepam in people with Major Depressive Disorder, run by Eli Lilly and Company at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- LY2216684 and Lorazepam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2010to Feb 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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).
- 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 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 acute narrow angle glaucoma.
- Have Gilbert's Syndrome
- Participants determined to be unsuitable by the investigator for any reason.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
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
About this study
Official title: Effect of LY2216684 on the Pharmacokinetics and Pharmacodynamics of Lorazepam in Healthy Subjects
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
- Being tested
- LY2216684, Placebo, Lorazepam
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY2216684Drug
Administered orally
PlaceboDrug
Administered orally
LorazepamDrug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: LY2216684; Drug: Placebo; Drug: Lorazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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.
Measured: 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
Participants were instructed to press the 'Yes' response button as quickly as possible every time the word 'Yes' was presented on the computer screen. Fifty stimuli were presented with a varying inter-stimulus interval of between 1 and 3.5 seconds. Participant's reaction time to the stimulus was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit Vigilance Targets Detected
A target digit was pseudo-randomly selected and constantly displayed to the right of the computer screen. A series of 450 digits was then presented in the center of the computer screen at the rate of 150 per minute. The participant was required to press the 'Yes' button as quickly as possible every time a digit in the series matched the target digit. There were 45 targets. Percentage of target digits correctly detected was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit Vigilance Speed
A target digit was pseudo-randomly selected and constantly displayed to the right of the computer screen. A series of 450 digits was then presented in the center of the computer screen at the rate of 150 per minute. The participant was required to press the 'Yes' button as quickly as possible every time a digit in the series matched the target digit. There were 45 targets. Speed at which a participant detected target digits was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit False Alarms
A target digit was pseudo-randomly selected and constantly displayed to the right of the computer screen. A series of digits were then presented in the center of the computer screen at the rate of 150 per minute. The participant was required to press the 'Yes' button as quickly as possible every time a digit in the series matched the target digit. There were 45 targets. The number of false alarms (incorrect 'Yes' responses) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Choice Reaction Time
Participants were required to respond to the words 'Yes' and 'No' as they appeared on the computer screen by pressing the corresponding button as quickly as possible. There were 50 trials during which each stimulus word was chosen randomly with equal probability; there was a varying inter-stimulus interval of between 1 and 3.5 seconds. The time required to respond was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Choice Reaction Time Accuracy
Participants were required to respond to the words 'Yes' and 'No' as they appeared on the computer screen by pressing the corresponding button as quickly as possible. There were 50 trials during which each stimulus word was chosen randomly with equal probability; there was a varying inter-stimulus interval of between 1 and 3.5 seconds. The percentage of correct responses was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Numeric Working Memory Sensitivity Index (SI)
Working memory is a sum of accuracy measures from the numeric and spatial working memory tasks (sensitivity index [SI]). Working Memory SI is based on how fast the participant responds correctly and how many are correct responses. A high score reflects someone able to hold in memory for a prolonged period. A negative change from baseline reflects impairment compared to baseline.
A series of 5 digits were presented on a computer screen, one every 1.15 seconds, for the participant to hold in memory. This was followed by a series of 30 probe digits for each of which the participant had to decide whether it had appeared in the original series of digits and press the corresponding 'Yes' or 'No' response button as quickly as possible. This procedure was repeated 2 times using 2 different series and probes. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Numeric Working Memory Speed
A series of 5 digits were presented on a computer screen, one every 1.15 seconds, for the participant to hold in memory. This was followed by a series of 30 probe digits for each of which the participant had to decide whether it had appeared in the original series of digits and press the corresponding 'Yes' or 'No' response button as quickly as possible. This procedure was repeated a further 2 times using 2 different series and probes. The time required to press the corresponding 'Yes' or 'No' response button in response to the probe digit is presented. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Immediate Word Recall Accuracy
The participant was given a series of words to commit to memory. Immediately after the last word was presented, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The percentage of words correctly recalled (present on the original list of words) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Immediate Word Recall Errors
The participant was given a series of words to commit to memory. Immediately after the last word was presented, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The number of words incorrectly recalled (not on the original list of words) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Delayed Word Recall Accuracy
The participant was given a series of words to commit to memory. After a delay of approximately 15-20 minutes, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The percentage of words correctly recalled (present on the original list of words) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Delayed Word Recall Errors
The participant was given a series of words to commit to memory. After a delay, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The number of incorrect words was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Word Recognition Sensitivity Index (SI)
Word Recognition SI is based on how fast the participant responds correctly and how many are correct responses. SI ranging from zero (chance performance) to one (perfect accuracy). Higher SI indicates better cognitive function. A negative change from baseline reflects impairment compared to baseline.
The original words from Word Presentation plus 15 distractor words were presented one at a time in a randomized order. For each word, the participant was required to indicate whether they recognized it from the original list of words by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following each response, there was a delay of 1 second before the next word was presented. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Word Recognition Speed
The original words from Word Presentation plus 15 distractor words were presented one at a time in a randomized order. For each word, the participant was required to indicate whether they recognized it from the original list of words by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following each response, there was a delay of 1 second before the next word was presented. The time required to press the corresponding 'Yes' or 'No' response button in response to the word was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Picture Recognition Sensitivity Index (SI)
Picture Recognition SI is based on how fast the participant responds correctly and how many are correct responses. SI ranging from zero (chance performance) to one (perfect accuracy). Higher SI indicates better cognitive function. A negative change from baseline reflects impairment compared to baseline.
The original pictures from Picture Presentation plus 20 distractor pictures were presented one at a time. For each picture, the participant was required to indicate whether they recognized it from the original series of pictures by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following the response, there was a delay of 1 second before the next pictures was presented. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Picture Recognition Speed
The original pictures from Picture Presentation plus 20 distractor pictures were presented one at a time. For each picture, the participant was required to indicate whether they recognized it from the original series of pictures by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following the response, there was a delay of 1 second before the next pictures was presented. The time required to press the corresponding 'Yes' or 'No' response button in response to the picture was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Tracking Average Distance From Target
The participant used a joystick to track a randomly moving target on the computer screen. The distance from the target was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Postural Stability
The ability to stand upright without moving was assessed using equipment modeled on the Wright Ataxia-meter. To measure movements, a cord was attached to the participant who was required to stand for one minute, as still as possible, with feet apart and eyes closed. The amount of sway is expressed as the total angular movement calibrated in units of one-third degree of angle of sway.
The amount of sway is expressed as the total angular movement in the antero-posterior plane and calibrated in units of one-third degree of angle of sway. Higher result indicates better postural stability. A negative change from baseline reflects impairment compared to baseline. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Alertness
The participant was required to rate how they felt "at this moment" on sixteen 10 centimeter visual analogue scales. The scale endpoints were anchored using polar word pairs such as 'drowsy-alert', 'clumsy-well coordinated', 'mentally slow-quick witted' and 'incompetent-proficient'. Responses from the 16 scales were scored to yield 3 main factors: Self-rated Alertness, Self-rated Contentment, and Self-rated Calmness. The possible range of scores are 0 to 100 for each factor and are represented in millimeters on the 10 centimeter line with higher numbers indicating greater alertness. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Contentment
The participant was required to rate how they felt "at this moment" on sixteen 10 centimeter visual analogue scales. The scale endpoints were anchored using polar word pairs such as 'drowsy-alert', 'clumsy-well coordinated', 'mentally slow-quick witted' and 'incompetent-proficient'. Responses from the 16 scales were scored to yield 3 main factors: Self-rated Alertness, Self-rated Contentment, and Self-rated Calmness. The possible range of scores are 0 to 100 for each factor and are represented in millimeters on the 10 centimeter line with higher numbers indicating greater contentment. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Calmness
The participant was required to rate how they felt "at this moment" on sixteen 10 centimeter visual analogue scales. The scale endpoints were anchored using polar word pairs such as 'drowsy-alert', 'clumsy-well coordinated', 'mentally slow-quick witted' and 'incompetent-proficient'. Responses from the 16 scales were scored to yield 3 main factors: Self-rated Alertness, Self-rated Contentment, and Self-rated Calmness. The possible range of scores are 0 to 100 for each factor and are represented in millimeters on the 10 centimeter line with higher numbers indicating greater calmness. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment*time.
Measured: Baseline, 2, 4, 8 hours on Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2011 (estimated)
- Study startDec 2010
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275144
- Sponsor's protocol ID
- 12596
- Other IDs
- H9P-EW-LNCG
- Status last verified
- Nov 2018
- First submitted
- 10 Jan 2011
- Last updated
- 11 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of LY2216684 on the Pharmacokinetics and Pharmacodynamics of Lorazepam in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01275144
- Acronym / sponsor ID
- 12596
- Conditions
- Major Depressive Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 12 Jan 2011 (estimated)
- Results
- Posted 11 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LY2216684+lorazepam, placebo+lorazepam | Experimental | Drug: LY2216684, Drug: Placebo, Drug: LorazepamOral 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. |
| Placebo+Lorazepam, LY2216684+Lorazepam | Experimental | Drug: LY2216684, Drug: Placebo, Drug: LorazepamOral 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY2216684Administered orally | Drug | LY2216684+lorazepam, placebo+lorazepam, Placebo+Lorazepam, LY2216684+Lorazepam |
| PlaceboAdministered orally | Drug | LY2216684+lorazepam, placebo+lorazepam, Placebo+Lorazepam, LY2216684+Lorazepam |
| LorazepamAdministered orally | Drug | LY2216684+lorazepam, placebo+lorazepam, Placebo+Lorazepam, LY2216684+Lorazepam |
Primary outcome
Pharmacokinetics of Lorazepam, Maximum Plasma Concentration (Cmax)
Time frame: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose
The geometric least squares mean and 90% Confidence Interval are presented. Geometric least squares mean corrected for participant, treatment and random error.
Pharmacokinetics of Lorazepam, Time to Maximum Plasma Concentration (Tmax)
Time frame: 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 (∞)
Time frame: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose
The geometric least squares mean and 90% Confidence Interval are presented. Geometric least squares mean corrected for participant, treatment and random error.
21 secondary outcomes
Change From Baseline in Cognitive Function-Simple Reaction Time
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit Vigilance Targets Detected
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit Vigilance Speed
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit False Alarms
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Choice Reaction Time
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Choice Reaction Time Accuracy
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Numeric Working Memory Sensitivity Index (SI)
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Numeric Working Memory Speed
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Immediate Word Recall Accuracy
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Immediate Word Recall Errors
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Delayed Word Recall Accuracy
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Delayed Word Recall Errors
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Word Recognition Sensitivity Index (SI)
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Word Recognition Speed
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Picture Recognition Sensitivity Index (SI)
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Picture Recognition Speed
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Tracking Average Distance From Target
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Postural Stability
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Alertness
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Contentment
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Calmness
Time frame: Baseline, 2, 4, 8 hours on Day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY2216684 and Lorazepam in people with Major Depressive Disorder, run by Eli Lilly and Company at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of Lorazepam, Maximum Plasma Concentration (Cmax) (time frame: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2019.