Healthy Participants
Conditions
Brief summary
This will be a 2-part, randomized, participant- and investigator-blind study in healthy males and females. Part A of this study is to determine a safe and tolerable single oral dose of LY3009104 that yields drug exposures slightly exceeding typical exposures anticipated from repeated administration of an efficacious dose to participants. The concentration of the drug in the blood stream will be measured and information about any side effects that may occur will also be collected. Part B of this study is to evaluate the effect of LY3009104 on the electrical activity of the heart as measured by electrocardiogram (ECG) in relation to placebo following a single oral dose.
Interventions
Sponsors
Incyte Corporation
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females as determined by medical history and physical examination. Are drug free, disease free, and no cardiac abnormalities. * 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 a clinically normal screening ECG with a measurable QT interval as judged by the investigator, and which in Part B allows accurate measurements of QT interval.
Exclusion criteria
* Have a history or presence of 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 an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study or affects or confounds the corrected QT (QTc) analysis or have QTc greater than 450 milliseconds (msec). * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | Part B, Periods 1 through 3: Baseline, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 12 h, and 24 h postdose | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using the population-corrected formula: QTcP = QT/RR\^beta, where beta is the population correction factor computed from a log-linear model (ln) QT = alpha+beta\*ln RR fitted to all Day -1 and Day 1 predose QT and RR measurements in all periods for all participants. Baseline is the average of data collected for 2 hours before dosing on Day 1 of each period \[-2 hours (h), -1.5 h, -1 h, -0.5 h, and 0 h\]. The QTcP interval was not assessed during Part A of the study, as specified in the protocol. The QTcP interval at 1 h, 2 h, and 4 h postdose for moxifloxacin was compared to placebo to establish assay sensitivity. |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | Parts A and B, Periods 1 through 3: Predose and 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 12 h, 24 h, 36 h, 48 h after administration of study drug | — |
| Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity [AUC(0-inf)] of LY3009104 | Parts A and B, Periods 1 through 3: Predose and 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 12 h, 24 h, 36 h, 48 h after administration of study drug | — |
| Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Baseline through study completion and 30-day follow-up | The number of participants with treatment-emergent adverse events (TEAEs) or treatment-emergent SAEs considered by the investigator to be related to study drug is reported. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
Countries
United States
Participant flow
Pre-assignment details
The study had 2 parts. Part A: single-dose, dose-escalating study of LY3009104 \[up to 40 milligrams (mg)\] or placebo administered in each period. Part B: assessed the electrophysiological effects of a single supratherapeutic LY3009104 dose compared to a positive control (moxifloxacin) and placebo. Participants enrolled in either Part A or Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A (LY3009104 or Placebo) Participants were randomized to 1 of 3 treatment sequences during Part A of the study and received a single dose (LY3009104 or placebo) in each period separated by a washout of at least 3 days. LY3009104 was administered as either 20-milligrams (mg), 30-mg or 40-mg dose. | 9 |
| Part B (LY3009104, Moxifloxacin, or Placebo) Participants were randomized to 1 of 6 treatment sequences during Part B of the study and received a single dose (LY3009104, moxifloxacin, or placebo) in each period separated by a washout of at least 3 days. LY3009104 was administered as a 40-mg dose. Moxifloxacin was administered as a 400-mg tablet. | 53 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention and Washout Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Second Intervention and Washout Period 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A (LY3009104 or Placebo) | Part B (LY3009104, Moxifloxacin, or Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 15.4 | 39.9 years STANDARD_DEVIATION 11.3 | 40.8 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 21 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 32 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 12 Participants | 13 Participants |
| Race/Ethnicity, Customized More than 1 race | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 39 Participants | 47 Participants |
| Region of Enrollment United States | 9 Participants | 53 Participants | 62 Participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 43 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 8 | 1 / 6 | 2 / 6 | 0 / 5 | 8 / 52 | 6 / 53 | 7 / 53 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 52 | 0 / 53 | 0 / 53 |
Outcome results
Primary
Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and is calculated from electrocardiogram (ECG) data. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between 2 R waves. Using the population-corrected formula: QTcP = QT/RR\^beta, where beta is the population correction factor computed from a log-linear model (ln) QT = alpha+beta\*ln RR fitted to all Day -1 and Day 1 predose QT and RR measurements in all periods for all participants. Baseline is the average of data collected for 2 hours before dosing on Day 1 of each period \[-2 hours (h), -1.5 h, -1 h, -0.5 h, and 0 h\]. The QTcP interval was not assessed during Part A of the study, as specified in the protocol. The QTcP interval at 1 h, 2 h, and 4 h postdose for moxifloxacin was compared to placebo to establish assay sensitivity.
Time frame: Part B, Periods 1 through 3: Baseline, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 12 h, and 24 h postdose
Population: Participants enrolled in Part B of the study who had at least 1 dose of study drug (LY3009104, moxifloxacin, or placebo).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 1 h postdose (n=52, 53, 53) | -2.5 milliseconds (msec) | Standard Deviation 4.9 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 1.5 h postdose (n=52, 53, 53) | -1.7 milliseconds (msec) | Standard Deviation 3.9 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 2 h postdose (n=52, 53, 53) | -1.4 milliseconds (msec) | Standard Deviation 6.5 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 3 h postdose (n=52, 53, 53) | -2.8 milliseconds (msec) | Standard Deviation 5.7 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 4 h postdose (n=52, 53, 53) | -1.3 milliseconds (msec) | Standard Deviation 5.2 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 6 h postdose (n=51, 53, 53) | -1.3 milliseconds (msec) | Standard Deviation 8.3 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 12 h postdose (n=52, 52, 52) | -1.0 milliseconds (msec) | Standard Deviation 8.3 |
| Part B: Placebo | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 24 h postdose (n=52, 53, 53) | -1.6 milliseconds (msec) | Standard Deviation 6.1 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 2 h postdose (n=52, 53, 53) | -0.1 milliseconds (msec) | Standard Deviation 5.3 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 12 h postdose (n=52, 52, 52) | 0.8 milliseconds (msec) | Standard Deviation 6.6 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 3 h postdose (n=52, 53, 53) | -2.5 milliseconds (msec) | Standard Deviation 4.9 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 4 h postdose (n=52, 53, 53) | -0.8 milliseconds (msec) | Standard Deviation 6.2 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 6 h postdose (n=51, 53, 53) | -2.2 milliseconds (msec) | Standard Deviation 8.1 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 1 h postdose (n=52, 53, 53) | -2.4 milliseconds (msec) | Standard Deviation 5 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 1.5 h postdose (n=52, 53, 53) | 0.1 milliseconds (msec) | Standard Deviation 5.5 |
| Part B: 40 mg LY3009104 | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 24 h postdose (n=52, 53, 53) | -0.8 milliseconds (msec) | Standard Deviation 6.7 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 2 h postdose (n=52, 53, 53) | 9.5 milliseconds (msec) | Standard Deviation 6.9 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 1.5 h postdose (n=52, 53, 53) | 9.3 milliseconds (msec) | Standard Deviation 5.8 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 1 h postdose (n=52, 53, 53) | 9.7 milliseconds (msec) | Standard Deviation 5.8 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 3 h postdose (n=52, 53, 53) | 9.2 milliseconds (msec) | Standard Deviation 6.2 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 12 h postdose (n=52, 52, 52) | 5.9 milliseconds (msec) | Standard Deviation 7.6 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 6 h postdose (n=51, 53, 53) | 5.5 milliseconds (msec) | Standard Deviation 7.3 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 4 h postdose (n=52, 53, 53) | 9.9 milliseconds (msec) | Standard Deviation 5.5 |
| Part B: Moxifloxacin | Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval | 24 h postdose (n=52, 53, 53) | 3.4 milliseconds (msec) | Standard Deviation 5.5 |
90% CI: [-1.65, 2.12]
90% CI: [-0.079, 3.69]
90% CI: [-0.446, 3.32]
90% CI: [-1.42, 2.35]
90% CI: [-1.18, 2.59]
90% CI: [-2.68, 1.1]
90% CI: [-0.182, 3.6]
90% CI: [-0.921, 2.85]
90% CI: [10, 14.5]
90% CI: [8.74, 13.3]
90% CI: [8.87, 13.4]
Primary
Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs)
The number of participants with treatment-emergent adverse events (TEAEs) or treatment-emergent SAEs considered by the investigator to be related to study drug is reported. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through study completion and 30-day follow-up
Population: Enrolled participants who had at least 1 dose of study drug (LY3009104, moxifloxacin, or placebo) during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Placebo | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 0 Participants |
| Part B: Placebo | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: 40 mg LY3009104 | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 0 Participants |
| Part B: 40 mg LY3009104 | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: Moxifloxacin | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: Moxifloxacin | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 1 Participants |
| Part B: 40 mg LY3009104 | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: 40 mg LY3009104 | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 0 Participants |
| Part B: Placebo | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 5 Participants |
| Part B: Placebo | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: 40 mg LY3009104 | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 5 Participants |
| Part B: 40 mg LY3009104 | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: Moxifloxacin | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related SAE | 0 Participants |
| Part B: Moxifloxacin | Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Drug-Related TEAE | 5 Participants |
Primary
Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity [AUC(0-inf)] of LY3009104
Time frame: Parts A and B, Periods 1 through 3: Predose and 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 12 h, 24 h, 36 h, 48 h after administration of study drug
Population: Randomized participants who received at least 1 dose of LY3009104 and had a predose and at least 1 postdose blood draw for AUC assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part B: Placebo | Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity [AUC(0-inf)] of LY3009104 | 3960 hours*nanomoles per liter (h*nmol/L) | Geometric Coefficient of Variation 27 |
| Part B: 40 mg LY3009104 | Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity [AUC(0-inf)] of LY3009104 | 5480 hours*nanomoles per liter (h*nmol/L) | Geometric Coefficient of Variation 19 |
| Part B: Moxifloxacin | Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity [AUC(0-inf)] of LY3009104 | 8490 hours*nanomoles per liter (h*nmol/L) | Geometric Coefficient of Variation 14 |
| Part B: 40 mg LY3009104 | Pharmacokinetics: Area Under the Concentration Curve From Time 0 to Infinity [AUC(0-inf)] of LY3009104 | 6440 hours*nanomoles per liter (h*nmol/L) | Geometric Coefficient of Variation 26 |
Primary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104
Time frame: Parts A and B, Periods 1 through 3: Predose and 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 12 h, 24 h, 36 h, 48 h after administration of study drug
Population: Randomized participants who received at least 1 dose of LY3009104.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part B: Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 578 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 28 |
| Part B: 40 mg LY3009104 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 734 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 14 |
| Part B: Moxifloxacin | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 1270 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 13 |
| Part B: 40 mg LY3009104 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 741 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 33 |