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Phase 1 Completed N=28 Randomized Double-blind Treatment

A Study of the Effect of LY2216684 on Lorazepam

Source: ClinicalTrials.gov NCT01275144 ↗
Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Mar 2019
Primary outcomePrimary: Pharmacokinetics of Lorazepam, Maximum Plasma Concentration (Cmax) — 9.620; 10.720 nanograms per milliliter (ng/mL)

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Pharmacokinetics of Lorazepam, Maximum Plasma Concentration (Cmax)
9.620; 10.720
PRIMARY
Pharmacokinetics of Lorazepam, Time to Maximum Plasma Concentration (Tmax)
3.00; 2.00 0.0021 sig
PRIMARY
Pharmacokinetics of Lorazepam, Area Under the Plasma Concentration Curve (AUC) From Time 0 to Infinity (∞)
207; 199
SECONDARY
Change From Baseline in Cognitive Function-Simple Reaction Time
5.0102; 23.9962; 27.9731; 40.0858; 13.1424; 10.0183
SECONDARY
Change From Baseline in Cognitive Function-Digit Vigilance Targets Detected
-3.5852; -3.5577; -2.4745; -4.1927; -2.5534; -1.9702
SECONDARY
Change From Baseline in Cognitive Function-Digit Vigilance Speed
20.1712; 12.0238; 14.7702; 12.1391; 9.8277; 2.5073
SECONDARY
Change From Baseline in Cognitive Function-Digit False Alarms
1.0204; 0.7296; 0.1990; 1.0510; 0.4490; 0.7653
SECONDARY
Change From Baseline in Cognitive Function-Choice Reaction Time
28.2448; 8.4745; 8.9837; 10.6866; 9.7930; -13.1780
SECONDARY
Change From Baseline in Cognitive Function-Choice Reaction Time Accuracy
-1.2292; -0.4851; -1.3720; -1.2708; -0.5863; -1.1994
SECONDARY
Change From Baseline in Cognitive Function-Numeric Working Memory Sensitivity Index (SI)
-0.00764; 0.003388; -0.02121; -0.00511; 0.007112; -0.01865
SECONDARY
Change From Baseline in Cognitive Function-Numeric Working Memory Speed
58.2923; 72.0037; 8.1891; 25.5894; -33.6927; -14.5106
SECONDARY
Change From Baseline in Cognitive Function-Immediate Word Recall Accuracy
-2.2751; -3.6767; -7.2744; -5.8195; -4.4166; -4.1524
SECONDARY
Change From Baseline in Cognitive Function-Immediate Word Recall Errors
-0.1582; 0.1225; 0.05605; 0.2297; 0.05605; 0.3011
SECONDARY
Change From Baseline in Cognitive Function-Delayed Word Recall Accuracy
-2.0338; -6.2980; -10.8423; -8.2034; -11.5566; -6.0595
SECONDARY
Change From Baseline in Cognitive Function-Delayed Word Recall Errors
0.1535; 0.6323; 0.6535; 0.8108; 0.6177; 0.4180
SECONDARY
Change From Baseline in Cognitive Function-Word Recognition Sensitivity Index (SI)
-0.08834; -0.07719; -0.06242; -0.1983; -0.1523; -0.1524
SECONDARY
Change From Baseline in Cognitive Function-Word Recognition Speed
-13.7645; -6.3483; -39.5052; -25.9919; -40.9574; -133.24
SECONDARY
Change From Baseline in Cognitive Function-Picture Recognition Sensitivity Index (SI)
0.02080; -0.03440; -0.04431; -0.06015; -0.1054; -0.09855
SECONDARY
Change From Baseline in Cognitive Function-Picture Recognition Speed
57.2341; 144.67; 51.7809; 62.2059; -59.9669; -23.2941
SECONDARY
Change From Baseline in Cognitive Function-Tracking Average Distance From Target
0.3850; -0.3614; 6.1672; -0.1104; 0.3743; -0.6036
SECONDARY
Change From Baseline in Cognitive Function-Postural Stability
-1.5464; 9.1392; 0.1965; 2.1857; -0.9571; -1.6429
SECONDARY
Change From Baseline in Cognitive Function-Self-rated Alertness
5.1411; 3.2597; 3.6887; 4.0018; 3.7205; 3.1287
SECONDARY
Change From Baseline in Cognitive Function-Self-rated Contentment
3.1100; 1.3686; 3.0171; 3.3829; 3.3743; 0.01857
SECONDARY
Change From Baseline in Cognitive Function-Self-rated Calmness
-0.9651; 0.3401; 1.4099; -1.3564; 3.4635; 0.3936

Eligibility Criteria

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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 millim
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01275144). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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