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A Study of LY3154885 in Healthy Participants

Phase 1
Terminated
Conditions
Healthy
Interventions
Drug: Placebo - Capsule
Drug: LY3154885 - Capsule
Drug: LY3154885 - Tablet
Registration Number
NCT04014361
Lead Sponsor
Eli Lilly and Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
36
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
LY3154885 - Part DLY3154885 - TabletPart D was not initiated.
Placebo - Part APlacebo - CapsulePlacebo administered orally in one of three study periods.
Placebo + Itraconazole - Part BPlacebo - CapsulePlacebo administered orally during period 1 followed by 200 mg Itraconazole administered orally on 10 consecutive days and then placebo co-administered with 200 mg itraconazole orally during period 2.
45 mg LY3154885 + Itraconazole - Part BLY3154885 - Capsule45 mg LY3154885 administered orally in period 1 followed by 200 mg Itraconazole administered orally on 10 consecutive days and then 45 mg LY3154885 co-administered with 200 mg itraconazole orally during period 2.
LY3154885 - Part CLY3154885 - CapsulePart C was not initiated.
LY3154885 - Part ALY3154885 - Capsule15, 45, 100, 200, 300 or 375 milligrams (mg) LY3154885 administered orally in two of three study periods.
LY3154885 - Part DLY3154885 - CapsulePart D was not initiated.
Placebo - Part CPlacebo - CapsulePart C was not initiated.
45 mg LY3154885 + Itraconazole - Part BItraconazole45 mg LY3154885 administered orally in period 1 followed by 200 mg Itraconazole administered orally on 10 consecutive days and then 45 mg LY3154885 co-administered with 200 mg itraconazole orally during period 2.
Placebo + Itraconazole - Part BItraconazolePlacebo administered orally during period 1 followed by 200 mg Itraconazole administered orally on 10 consecutive days and then placebo co-administered with 200 mg itraconazole orally during period 2.
Primary Outcome Measures
NameTimeMethod
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug AdministrationBaseline through Study Completion (Up to 5 Months)

An SAE is any AE from this study that results in one of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

Secondary Outcome Measures
NameTimeMethod
Part A, PK: Area Under the Concentration Versus Time Curve to Infinity [AUC(0-∞)] of LY3154885Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post dose

Part A, PK: Area Under the Concentration Versus Time Curve to Infinity \[AUC(0-∞)\] of LY3154885

Part B, PK: Time to Maximum Plasma Concentration (Tmax) LY3154885Day 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.
Part B: PK: Maximum Concentration (Cmax) of LY3154885Day 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.

Part B: PK: Maximum Concentration (Cmax) of LY3154885

Part A, PK: Time to Maximum Plasma Concentration (Tmax) LY3154885Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post dose

Part A, PK: Time to Maximum Plasma Concentration (Tmax) LY3154885

Part B, PK: Area Under the Concentration Versus Time Curve to Infinity [AUC(0-∞)] of LY3154885Day 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.

Part B, PK: Area Under the Concentration Versus Time Curve to Infinity \[AUC(0-∞)\] of LY3154885

Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3154885Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post dose

Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3154885

Trial Locations

Locations (1)

Covance

🇺🇸

Dallas, Texas, United States

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