A Study of LY3009104 in Healthy Participants

• ClinicalTrials.gov Identifier: NCT01536951
• Recruitment Status: Completed
• First Posted: February 22, 2012
• Results First Posted: April 21, 2017
• Last Update Posted: June 6, 2017
• Sponsor: Eli Lilly and Company
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: February 16, 2012
• First Posted Date: February 22, 2012
• Results First Submitted Date: March 10, 2017
• Results First Posted Date: April 21, 2017
• Last Update Posted Date: June 6, 2017
• Study Start Date: February 2012
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2017)

• Change From Baseline Through 24 Hours Postdose in Population-Corrected QT (QTcP) Interval [ 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 ]
  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 [ 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 ]
• 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 ]
• Number of Participants With 1 or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 16, 2012)

• Number of participants with one or more drug related adverse events (AEs) or any serious AEs [ Time Frame: Up to 48 hours after administration of study drug ]
• Part A. Pharmacokinetics: maximum concentration (Cmax) of LY3009104 [ Time Frame: Up to 48 hours after administration of study drug ]
• Part A. Pharmacokinetics: area under the concentration curve (AUC) of LY3009104 [ Time Frame: Up to 48 hours after administration of study drug ]
• Part B. Change from baseline through 24 hours post-dose in QTcF interval between LY3009104 and placebo [ Time Frame: Baseline, 24 hours post-dose ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LY3009104 in Healthy Participants
• Official Title: A Placebo-Controlled, Single Dose, Dose Escalation (Part A) and a Placebo- and Positive-Controlled Study of the Effect on the Electrocardiographic QT Interval of a Single Dose (Part B) of LY3009104 in Healthy Subjects

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Healthy Participants

Intervention

• Drug: LY3009104
  administered orally
  Other Name: Baricitinib
• Drug: Placebo
  Administered orally
• Drug: moxifloxacin
  Administered orally

Study Arms

• Placebo Comparator: Placebo
  Placebo matching LY3009104 tablets in size and appearance will be administered orally in 1 out of 3 study periods in Part A and Part B.
  Intervention: Drug: Placebo
• Experimental: LY3009104

  Part A. Single escalating dose of up to 40 milligrams (mg) of LY3009104 administered orally in 2 out of 3 study periods separated by at least a 3 day wash-out period between each dose.

  Part B. Single dose of LY3009104 determined in Part A administered orally in 1 out of 3 study periods separated by at least a 3 day wash-out period between each period.

  Intervention: Drug: LY3009104
• Active Comparator: 400 mg moxifloxacin
  Part B. 400 mg moxifloxacin will be administered orally in 1 out of 3 study periods separated by at least a 3 day wash-out period between each period.
  Intervention: Drug: moxifloxacin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 10, 2017): 62
• Original Estimated Enrollment (submitted: February 16, 2012): 69
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01536951
• Other Study ID Numbers: 14448; I4V-MC-JADO ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Incyte Corporation

Investigators

• Study Director: 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

• PRS Account: Eli Lilly and Company
• Verification Date: May 2017