Clinical trial NCT04014361: A Study of LY3154885 in Healthy Participants
Official title: Single- and Multiple-Ascending Dose, Safety, Tolerability, and Pharmacokinetic Study With LY3154885 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 36
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to learn more about the safety and side effects of LY3154885 when given by mouth to healthy participants. The study will have up to four parts. Each participant will enroll in only one part. The study will last up to 70 days for each participant, including screening and follow-up.


Eligibility criteria: Inclusion Criteria:

* Are overtly healthy males or females, as determined by medical history and physical examination
* Male participants:

  * Men, regardless of their fertility status, with partners who are nonpregnant women of childbearing potential, must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use condoms with spermicide as well as 1 additional highly effective (\<1% failure rate) method of contraception or effective method of contraception (such as diaphragms with spermicide) for 3 months following dosing
  * Men with pregnant partners should use condoms with spermicide during intercourse for the duration of the study or for 3 months following dosing, whichever is longer
  * Men who are in exclusively same-sex relationships (as their preferred and usual lifestyle) or with female partners of non-childbearing potential are not required to use contraception
  * Men should refrain from sperm donation for the duration of the study or for 3 months following the last dose of study drug, whichever is longer
* Female participants of non-childbearing potential, including those who are:

  * Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, confirmed tubal ligation, or tubal occlusion) or congenital anomaly such as Müllerian agenesis; or
  * Postmenopausal, defined as 1 of the following:

    * A woman at least 50 years of age with an intact uterus, not on hormone replacement therapy, who has had either:

      * Cessation of menses for at least 1 year; or
      * At least 6 months of spontaneous amenorrhea with a follicle-stimulating hormone level ≥40 milli-international units per milliliter (mIU/mL) at screening
    * A woman at least 55 years of age, not on hormone replacement therapy, who has had at least 6 months of spontaneous amenorrhea; or
    * A woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy
* Have a body mass index (BMI) of 18.0 to 35.0 kilograms per square meter (kg/m²), inclusive

Exclusion Criteria:

* Have a marked baseline prolongation of/corrected QT (QTc) interval (for example, repeated demonstration of a QTcB interval \>450 milliseconds \[msec\] for males or \>470 msec for females);

  * A history of additional risk factors for Torsades de Pointes (for example, heart failure, hypokalemia, family history of Long QT Syndrome);
  * The use of concomitant medications that prolong the QT/QTc interval
* Have an abnormal blood pressure (BP) (taken after the participant has been in a supine position for at least 5 minutes) for the population, as determined by a systolic BP \>140 millimeters of mercury (mmHg) or a diastolic BP \>90 mmHg at screening or a preexisting history of hypertension. Up to 2 additional measurements may be taken after an appropriate resting interval at screening to confirm eligibility
* Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (such as Cushing syndrome, hyperthyroidism, hyperaldosteronism), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational medicinal product (IMP); or of interfering with the interpretation of data
* Have a history of or current significant psychiatric disorders

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through Study Completion (Up to 5 Months)
Secondary outcomes:
measure: Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3154885
timeFrame: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post dose
measure: Part B: PK: Maximum Concentration (Cmax) of LY3154885
timeFrame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post dose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72 and 96 hours post dose.
measure: Part A, PK: Time to Maximum Plasma Concentration (Tmax) LY3154885
timeFrame: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post dose
measure: Part B, PK: Time to Maximum Plasma Concentration (Tmax) LY3154885
timeFrame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post dose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72 and 96 hours post dose.
measure: Part A, PK: Area Under the Concentration Versus Time Curve to Infinity [AUC(0-∞)] of LY3154885
timeFrame: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post dose
measure: Part B, PK: Area Under the Concentration Versus Time Curve to Infinity [AUC(0-∞)] of LY3154885
timeFrame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post dose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72 and 96 hours post dose.
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: