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LY3009104

Phase 2

Arthritis, Rheumatoid | Small molecule | Immunology |Eli Lilly and Company|Last Updated: Apr 13, 2018

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment301

FDA Designations

No designations recorded

Clinical trial landscape

LY3009104 · 5 trials · 5 indications

Phase 2 1Phase 1 4
NCT01185353A Study in Participants With Rheumatoid Arthritis on Background Methotrexate TherapyArthritis, Rheumatoid
COMPLETED301 Analytics
PHASE2COMPLETED
A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy
Arthritis, RheumatoidUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12
Baseline through Week 12

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100.

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.

Pharmacokinetics: Plasma Concentration-Time Curve (AUC)
Predose up to 48 hours postdose for each of the 4 treatment periods

The area under the concentration-time curve from time 0 to infinity \[AUC(0-inf)\] is reported for participants who received either LY3009104 tablets or capsules in a fasted or fed state.

Percentage of the Total Radioactive Dose Administered Excreted From Urine and Feces
Baseline up to 120 hours
Number of Participants With Clinically Significant Effects
Days 1-10 for Cohorts 1 & 2, Days 1-7 for single dose of Cohorts 3 & 4, Days 8-31 for multiple doses

Adverse events were considered clinically significant effects. A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.

Secondary Endpoints

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response
Baseline through Week 12
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24
Baseline through Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128
Baseline through Weeks 76 and 128
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
1 mg LY3009104 once dailyEXPERIMENTALAdministered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
2 mg LY3009104 once dailyEXPERIMENTALAdministered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
4 mg LY3009104 once dailyEXPERIMENTALAdministered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
8 mg LY3009104 once dailyEXPERIMENTALAdministered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Placebo once dailyPLACEBO_COMPARATORPlacebo administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
2 mg LY3009104 twice dailyEXPERIMENTAL(Not utilized in Part A) After 12 weeks treatment with 1 mg LY3009104 once daily or Placebo once daily in Part A, administered orally twice daily for 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
PlaceboPLACEBO_COMPARATORPlacebo matching LY3009104 tablets in size and appearance will be administered orally in 1 out of 3 study periods in Part A and Part B.
LY3009104EXPERIMENTALPart 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.
400 mg moxifloxacinACTIVE_COMPARATORPart 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.
LY3009104 Reference FormulationEXPERIMENTAL8 milligrams (mg) LY3009104 (two 4-mg phosphate salt capsules), administered orally in the fasted state, once only. There will be a washout period of 5 to 7 days between doses of study drug.
LY3009104 Test Formulation 1EXPERIMENTAL8 mg LY3009104 (one 8-mg smaller particle free base tablet), administered orally in the fasted state, once only. There will be a washout period of 5 to 7 days between doses of study drug.
LY3009104 Test Formulation 2EXPERIMENTAL8 mg LY3009104 (one 8-mg larger particle free base tablet), administered orally in the fasted state, once only. There will be a washout period of 5 to 7 days between doses of study drug.
LY3009104 Test Formulation 2 + MealEXPERIMENTAL8 mg LY3009104 (one 8-mg larger particle free base tablet), administered orally with high-fat/high calorie meal, once only. There will be a washout period of 5 to 7 days between doses of study drug.
2 mg LY3009104 (Cohort 1)EXPERIMENTAL2mg administered once on day 1 (single dose)
5 mg LY3009104 (Cohort 2)EXPERIMENTAL5mg administered once on day 1 (single dose)
10 mg LY3009104 (Cohort 3)EXPERIMENTAL10 mg administered on day 1 (single dose) and following a 7 day washout period, administered once daily for 10 days (multiple dose)
14 mg LY3009104 (Cohort 4 )EXPERIMENTAL14 mg administered on day 1 (single dose) and following a 7 day washout period, administered once daily for 10 days (multiple dose)

Interventions

NameTypeDescription
LY3009104DRUGAdministered orally
PlaceboDRUGAdministered orally
MethotrexateDRUGAdministered orally as background therapy
moxifloxacinDRUGAdministered orally
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Eligibility Criteria

Age Range18 Years to 75 Years
SexALL
Healthy VolunteersNo
Study Sites68

Inclusion Criteria: * Must have active RA * Must regularly use methotrexate (MTX) for at least 12 weeks before your participation in this study * Must have American College of Rheumatology (ACR) functional class I, II, or III * Must have C-reactive protein (CRP) measurement \> 1.2 times upper limit...

Countries:United StatesCroatiaCzechiaHungaryIndiaMexicoPolandRomaniaUkraineSingapore
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Frequently asked questions about LY3009104

What is LY3009104 used for?

LY3009104 is an investigational small molecule being studied for the treatment of rheumatoid arthritis and chronic inflammatory disorders. It has been evaluated in clinical trials for use in patients with rheumatoid arthritis on background methotrexate therapy, as well as in healthy volunteers for safety and pharmacokinetic studies.

What does LY3009104 target?

LY3009104 is a small molecule developed by Eli Lilly and Company for immunology indications. While its specific molecular target is not disclosed in the available clinical trial information, it is being investigated for its potential to modulate inflammatory pathways in conditions like rheumatoid arthritis.

Who makes LY3009104?

LY3009104 is being developed by Eli Lilly and Company, a pharmaceutical company listed on the stock exchange under the ticker symbol LLY. The company has sponsored clinical trials evaluating this investigational drug in patients with rheumatoid arthritis and in healthy volunteers.

What phase is LY3009104 in?

LY3009104 has completed Phase 2 clinical development for rheumatoid arthritis. A Phase 2 trial (NCT01185353) involving 301 participants has been completed. Additionally, several Phase 1 studies in healthy volunteers have also been completed, but the drug is not approved and remains investigational.

What clinical trials is LY3009104 in?

LY3009104 has been studied in four completed clinical trials. The Phase 2 trial NCT01185353 evaluated the drug in 301 participants with rheumatoid arthritis on background methotrexate therapy. Phase 1 trials include NCT01247350, NCT01398475, and NCT01536951, which assessed safety, bioavailability, and food effects in healthy volunteers.

Is LY3009104 the same as baricitinib?

LY3009104 is also known as baricitinib, as indicated in the title of clinical trial NCT01247350, which refers to 'LY3009104(Baricitinib)'. This investigational drug is being developed by Eli Lilly and Company for rheumatoid arthritis and other inflammatory conditions.