RAjuvenate: A Study of LY3337641 in Rheumatoid Arthritis
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT02628028
Collaborator
(none)
286
71
8
23.8
4
0.2
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate the safety and effectiveness of LY3337641 in adults with rheumatoid arthritis (RA).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
286 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, 2-Part Phase 2 Study to Evaluate the Safety and Efficacy of LY3337641 in Adult Subjects With Rheumatoid Arthritis: The RAjuvenate Study
Actual Study Start Date
:
Aug 22, 2016
Actual Primary Completion Date
:
Apr 25, 2018
Actual Study Completion Date
:
Aug 15, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A 5 mg LY3337641 Given once a day for 4 weeks. |
Drug: LY3337641
Administered orally
|
| Experimental: Part A 10 mg LY3337641 Given once a day for 4 weeks. |
Drug: LY3337641
Administered orally
|
| Experimental: Part A 30 mg LY3337641 Given once a day for 4 weeks. |
Drug: LY3337641
Administered orally
|
| Placebo Comparator: Part A Placebo Given once a day for 4 weeks. |
Drug: Placebo
Administered orally
|
| Experimental: Part B 5 mg LY3337641 Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period. |
Drug: LY3337641
Administered orally
|
| Experimental: Part B 10 mg LY3337641 Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period. |
Drug: LY3337641
Administered orally
|
| Experimental: Part B 30 mg LY3337641 Given once a day for 12 weeks and an additional 52 weeks for Long-term extension (LTE) period. |
Drug: LY3337641
Administered orally
|
| Placebo Comparator: Part B Placebo Given once a day for 12 weeks. |
Drug: Placebo
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) or Adverse Events of Special Interest (AESIs) or Any Serious AEs (SAEs) in Part A [Up to 6 Weeks]
TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. Skin Rash was the only event that was considered an AESI. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious AEs, regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section.
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response in Part B [Week 12]
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and /or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
Secondary Outcome Measures
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response in Part B [Week 12]
ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using VAS, HAQ-DI and hsCRP. Participants with missing responses and/or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response in Part B [Week 12]
ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using VAS, HAQ-DI and hsCRP. Participants with missing responses and/or participants who discontinue study or drug before analysis timepoint are deemed non-responders.
- Change From Baseline in the Disease Activity Score (DAS) 28-high-sensitivity C-reactive Protein (hsCRP) in Part B [Baseline, Week 12]
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using VAS. DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
- Percentage of Participants Who Achieve Low Disease Activity Using DAS28-hsCRP in Part B [Week 12]
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using VAS. DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
- Percentage of Participants Who Achieve Clinical Remission Using DAS28-hsCRP in Part B [Week 12]
Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (participant global VAS). DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Clinical remission is defined as DAS28-hsCRP <2.6.
- Pharmacokinetics (PK): Clearance Parameter of LY3337641 [Part A: Weeks 1, 2, and 4, Day 1 (0.5 to 2 hours postdose); Part B: Weeks 2, 4, 8, and 12, Day 1 (0.5 to 2 hours postdose)]
Apparent total body clearance of drug after oral administration based on population PK analysis was evaluated. As prespecified per protocol, an overall population estimate of clearance is generated and data from Part A and B were combined for the analysis. The sparse data was then analyzed using population PK methods in Non linear Mixed Effects Model (NONMEM) to generate an overall population estimate of clearance.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Female subjects of childbearing potential test negative for pregnancy at screening and agree not to breastfeed
-
Female subjects: agree to use a reliable method of birth control from the start of screening until 28 days after the last dose of study drug or be of nonchildbearing potential
-
Male subjects: agree to use a reliable method of birth control from the start of screening until 2 weeks after the last dose of study drug or have undergone vasectomy
-
Have a diagnosis of RA based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism criteria
-
Have at least 1 of the following:
-
rheumatoid factor or anti-citrullinated peptide antibodies (ACPA) at screening OR
-
radiographs documenting bony erosions
-
Have active RA, defined as:
-
Part A: ≥3 swollen joints (based on 66-joint counts)
-
Part B:
-
≥6 swollen joints (based on 66-joint counts)
-
≥6 tender joints (based on 68-joint counts)
-
hsCRP levels greater than the upper limit of normal (ULN) OR positive for ACPA
-
Part B only: Have had inadequate response, loss of response, or intolerance to at least 1 synthetic OR biologic disease-modifying antirheumatic drug (DMARD)
Exclusion Criteria:
-
Have received any of the following:
-
Part B only: any prior treatment with a product directly targeting Bruton's tyrosine kinase (BTK) (marketed or investigational)
-
belimumab, natalizumab, or vedolizumab within 6 months prior to baseline
-
B-cell-depleting agents (such as rituximab) or other cell-depleting biologics (eg, anti-cluster of differentiation 3 (CD3) antibody) within 12 months prior to screening for Part A or at any time prior to screening for Part B
-
Have known hypogammaglobulinemia
-
Have hepatitis C virus, hepatitis B virus or human immunodeficiency virus
-
Have active tuberculosis (TB)
-
Are at high risk of infection or have recent evidence of clinically significant infection
-
Have had lymphoma, leukemia, or any malignancy within the previous 5 years except for treated basal cell or squamous epithelial carcinomas of the skin
-
Have received a live (attenuated) vaccine within 28 days prior to baseline or plan to receive one during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Desert Medical Advances | Palm Desert | California | United States | 92260 |
| 2 | Stanford University Hospital | Palo Alto | California | United States | 94304 |
| 3 | Denver Arthritis Center | Denver | Colorado | United States | 80230 |
| 4 | Innovative Research of West Florida | Clearwater | Florida | United States | 33756 |
| 5 | Jeffrey Alper MD Research | Naples | Florida | United States | 34102 |
| 6 | Sun Coast Clinical Research, Inc | New Port Richey | Florida | United States | 34652 |
| 7 | Lovelace Scientific Resources | Venice | Florida | United States | 34292 |
| 8 | Center for Arthritis & Osteoporosis | Elizabethtown | Kentucky | United States | 42701 |
| 9 | Clayton Medical Research | Saint Louis | Missouri | United States | 63117 |
| 10 | Rowan Regional Medical Center | Salisbury | North Carolina | United States | 28144 |
| 11 | PMG Research of Wilmington, LLC | Wilmington | North Carolina | United States | 28401 |
| 12 | Articularis Healthcare d/b/a/ Low Country Rheumatology, PA | North Charleston | South Carolina | United States | 29406 |
| 13 | Accurate Clinical Research | League City | Texas | United States | 77573 |
| 14 | Accurate Clinical Research | Nassau Bay | Texas | United States | 77058 |
| 15 | Rheumatology and Immunotherapy Center | Franklin | Wisconsin | United States | 53132 |
| 16 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Buenos Aires | Argentina | C1430EGF | |
| 17 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ciudad Autonoma de Buenos Aire | Argentina | C1015ABO | |
| 18 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ciudad Autonoma de Buenos Aire | Argentina | C1128AAF | |
| 19 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ciudad Autonoma de Buenos Aire | Argentina | C1204AAD | |
| 20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ciudad Autonoma de Buenos Aire | Argentina | C1426AAL | |
| 21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ciudad Autonoma de Buenos Aire | Argentina | c1440AAD | |
| 22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Cordoba | Argentina | X5000EDC | |
| 23 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Rosario | Argentina | S2000CFJ | |
| 24 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Rosario | Argentina | S2000PBJ | |
| 25 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Fernando | Argentina | B1646DBM | |
| 26 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Juan | Argentina | J5402DIL | |
| 27 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Miguel de Tucuman | Argentina | T4000AXL | |
| 28 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tucuman | Argentina | 4000 | |
| 29 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Maroochydore | Australia | 4558 | |
| 30 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Woodville South | Australia | 5011 | |
| 31 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Innsbruck | Austria | 6020 | |
| 32 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Wien | Austria | 1090 | |
| 33 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Firenze | Italy | 50139 | |
| 34 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Milano | Italy | 20157 | |
| 35 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Torino | Italy | 10154 | |
| 36 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Asahikawa | Japan | 070-8644 | |
| 37 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chiba | Japan | 275-8580 | |
| 38 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Fukuoka | Japan | 810-8539 | |
| 39 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Fukuoka | Japan | 810-8563 | |
| 40 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hokkaido | Japan | 060-0001 | |
| 41 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kitakyushu | Japan | 807-8556 | |
| 42 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nagano | Japan | 380-8582 | |
| 43 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Omura | Japan | 856-8562 | |
| 44 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sapporo | Japan | 060-0004 | |
| 45 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sapporo | Japan | 060-8648 | |
| 46 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sasebo | Japan | 857-1195 | |
| 47 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Sendai | Japan | 980-8574 | |
| 48 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Jung-gu | Korea, Republic of | 22332 | |
| 49 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seoul | Korea, Republic of | 04763 | |
| 50 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seoul | Korea, Republic of | 05030 | |
| 51 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seoul | Korea, Republic of | 06591 | |
| 52 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seoul | Korea, Republic of | 07345 | |
| 53 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Col. Roma | Mexico | 6700 | |
| 54 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Distrito Federal | Mexico | 3100 | |
| 55 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mexicali | Mexico | 21100 | |
| 56 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mexico City | Mexico | 06700 | |
| 57 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Elblag | Poland | 82-300 | |
| 58 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Gdansk | Poland | 80-546 | |
| 59 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nadarzyn | Poland | 05-830 | |
| 60 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Warsaw | Poland | 03-291 | |
| 61 | Office: Perez-De Jesus, Amarilis | Caguas | Puerto Rico | 00725 | |
| 62 | Mindful Medical Research | San Juan | Puerto Rico | 00918 | |
| 63 | Latin Clinical Trial Center | Santurce | Puerto Rico | 00909 | |
| 64 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bratislava | Slovakia | 85101 | |
| 65 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Zvolen | Slovakia | 96001 | |
| 66 | For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. | Pinelands | South Africa | 7405 | |
| 67 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Stellenbosch | South Africa | 7600 | |
| 68 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Umhlanga | South Africa | 4319 | |
| 69 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Alicante | Spain | 03570 | |
| 70 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bilbao | Spain | 48013 | |
| 71 | For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician. | Sevilla | Spain | 41010 |
Sponsors and Collaborators
- Eli Lilly and Company
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
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02628028
Other Study ID Numbers:
- 16173
- I8K-MC-JPDA
- 2015-003289-97
First Posted:
Dec 11, 2015
Last Update Posted:
Oct 9, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The study consist of 2-parts. Part A included participants with at least mildly active rheumatoid arthritis (RA) and Part B included participants with moderately to severely active RA. Long-term extension (LTE) period allowed eligible participants who completed Part B of study to receive LY3337641 up to an additional 52 weeks. |
| Arm/Group Title | Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo once daily (QD) for 4 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 4 weeks. | Participants received oral dose of placebo QD for 12 weeks. | Part B Dosing period: Participants received oral dose of 5 mg LY3337641 tablet QD for 12 weeks. Long-term extension (LTE) period: Participants who completed Part B of study received oral dose of 5 mg LY3337641 QD for an additional 52 weeks. | Participants received oral dose of 10 mg LY3337641 tablet QD for 12 weeks. Long-term extension (LTE) period: Participants who completed Part B of study received oral dose of 10 mg LY3337641 QD for an additional 52 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. Long-term extension (LTE) period: Participants who completed Part B of study received oral dose of 30 mg LY3337641 QD for an additional 52 weeks. |
| Period Title: Dosing Period | ||||||||
| STARTED | 9 | 9 | 10 | 8 | 62 | 63 | 62 | 63 |
| Received at Least 1dose of Study Drug | 9 | 9 | 10 | 8 | 62 | 63 | 62 | 63 |
| COMPLETED | 9 | 9 | 9 | 8 | 46 | 49 | 46 | 48 |
| NOT COMPLETED | 0 | 0 | 1 | 0 | 16 | 14 | 16 | 15 |
| Period Title: Dosing Period | ||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 61 | 58 | 61 |
| Placebo Re-randomized in LTE | 0 | 0 | 0 | 0 | 0 | 14 | 14 | 14 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 60 | 58 | 61 |
Baseline Characteristics
| Arm/Group Title | Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo once daily (QD) for 4 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 4 weeks. | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. | Total of all reporting groups |
| Overall Participants | 9 | 9 | 10 | 8 | 62 | 63 | 62 | 63 | 286 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
54.3
(11.43)
|
54.0
(11.75)
|
56.9
(6.44)
|
51.9
(5.72)
|
50.5
(8.75)
|
50.1
(9.20)
|
51.7
(9.36)
|
51.9
(8.91)
|
51.5
(9.09)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
8
88.9%
|
8
88.9%
|
9
90%
|
5
62.5%
|
54
87.1%
|
53
84.1%
|
56
90.3%
|
53
84.1%
|
246
86%
|
| Male |
1
11.1%
|
1
11.1%
|
1
10%
|
3
37.5%
|
8
12.9%
|
10
15.9%
|
6
9.7%
|
10
15.9%
|
40
14%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
4
44.4%
|
3
33.3%
|
3
30%
|
2
25%
|
34
54.8%
|
26
41.3%
|
23
37.1%
|
21
33.3%
|
116
40.6%
|
| Not Hispanic or Latino |
5
55.6%
|
6
66.7%
|
7
70%
|
6
75%
|
24
38.7%
|
29
46%
|
26
41.9%
|
23
36.5%
|
126
44.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
6.5%
|
8
12.7%
|
13
21%
|
19
30.2%
|
44
15.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||
| American Indian or Alaska Native |
2
22.2%
|
1
11.1%
|
1
10%
|
0
0%
|
1
1.6%
|
1
1.6%
|
0
0%
|
0
0%
|
6
2.1%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
7
11.3%
|
14
22.2%
|
9
14.5%
|
10
15.9%
|
40
14%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
11.1%
|
1
11.1%
|
0
0%
|
1
12.5%
|
1
1.6%
|
2
3.2%
|
2
3.2%
|
2
3.2%
|
10
3.5%
|
| White |
6
66.7%
|
7
77.8%
|
9
90%
|
7
87.5%
|
53
85.5%
|
46
73%
|
50
80.6%
|
51
81%
|
229
80.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
0
0%
|
1
0.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||||||||
| Puerto Rico |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
6.5%
|
2
3.2%
|
3
4.8%
|
5
7.9%
|
14
4.9%
|
| Argentina |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
15
24.2%
|
13
20.6%
|
15
24.2%
|
14
22.2%
|
57
19.9%
|
| United States |
6
66.7%
|
6
66.7%
|
6
60%
|
7
87.5%
|
12
19.4%
|
13
20.6%
|
15
24.2%
|
6
9.5%
|
71
24.8%
|
| Japan |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
6
9.7%
|
6
9.5%
|
6
9.7%
|
7
11.1%
|
25
8.7%
|
| Spain |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
3
4.8%
|
3
4.8%
|
6
9.5%
|
13
4.5%
|
| South Korea |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
5
7.9%
|
0
0%
|
3
4.8%
|
8
2.8%
|
| Austria |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
| Poland |
0
0%
|
0
0%
|
2
20%
|
1
12.5%
|
9
14.5%
|
9
14.3%
|
4
6.5%
|
7
11.1%
|
32
11.2%
|
| Italy |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
2
3.2%
|
2
3.2%
|
5
7.9%
|
10
3.5%
|
| Mexico |
3
33.3%
|
3
33.3%
|
2
20%
|
0
0%
|
10
16.1%
|
6
9.5%
|
7
11.3%
|
4
6.3%
|
35
12.2%
|
| South Africa |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3.2%
|
3
4.8%
|
5
8.1%
|
3
4.8%
|
13
4.5%
|
| Slovakia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3.2%
|
2
3.2%
|
4
1.4%
|
| Australia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
1
1.6%
|
0
0%
|
1
1.6%
|
3
1%
|
Outcome Measures
| Title | Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) or Adverse Events of Special Interest (AESIs) or Any Serious AEs (SAEs) in Part A |
|---|---|
| Description | TEAEs are any untoward medical occurrence that either occurs or worsens at any time after treatment baseline, and in the opinion of the investigators is possibly related to study drug. Skin Rash was the only event that was considered an AESI. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious AEs, regardless of whether or not they were possibly related to study drug, is located in the Reported Adverse Event section. |
| Time Frame | Up to 6 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug in Part A. |
| Arm/Group Title | Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo once daily (QD) for 4 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 4 weeks. |
| Measure Participants | 9 | 9 | 10 | 8 |
| TEAEs |
3
33.3%
|
1
11.1%
|
6
60%
|
2
25%
|
| AESIs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response in Part B |
|---|---|
| Description | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using visual analog scale (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and /or participants who discontinue study or drug before analysis timepoint are deemed non-responders. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug, for participants who completed or early discontinued dosing treatment period before the study was terminated in Part B. Missing values due to discontinuation of study or drug, or missing data were imputed using non-responder imputation (NRI). |
| Arm/Group Title | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. |
| Measure Participants | 54 | 56 | 52 | 55 |
| Number (95% Confidence Interval) [Percentage of Participants] |
48.1
534.4%
|
55.4
615.6%
|
44.2
442%
|
50.9
636.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 5 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.473 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 10 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.670 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 30 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.823 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Title | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response in Part B |
|---|---|
| Description | ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using VAS, HAQ-DI and hsCRP. Participants with missing responses and/or participants who discontinue study or drug before analysis timepoint are deemed non-responders. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug, for participants who completed or early discontinued dosing treatment period before the study was terminated in Part B. Missing values due to discontinuation of study or drug, or missing data were imputed using non-responder imputation (NRI). |
| Arm/Group Title | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. |
| Measure Participants | 54 | 56 | 52 | 55 |
| Number (95% Confidence Interval) [Percentage of Participants] |
27.8
308.9%
|
25.0
277.8%
|
15.4
154%
|
29.1
363.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 5 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.743 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 10 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.124 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 30 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.858 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Title | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response in Part B |
|---|---|
| Description | ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient's Global Assessment of Arthritis Pain using VAS, HAQ-DI and hsCRP. Participants with missing responses and/or participants who discontinue study or drug before analysis timepoint are deemed non-responders. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug, for participants who completed or early discontinued dosing treatment period before the study was terminated in Part B. Missing values due to discontinuation of study or drug, or missing data were imputed using non-responder imputation (NRI). |
| Arm/Group Title | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. |
| Measure Participants | 54 | 56 | 52 | 55 |
| Number (95% Confidence Interval) [Percentage of Participants] |
16.7
185.6%
|
8.9
98.9%
|
1.9
19%
|
16.4
205%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 5 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.199 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 10 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 30 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.863 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Title | Change From Baseline in the Disease Activity Score (DAS) 28-high-sensitivity C-reactive Protein (hsCRP) in Part B |
|---|---|
| Description | Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using VAS. DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug, for participants who completed or early discontinued dosing treatment period before the study was terminated in Part B. Missing values due to discontinuation of study or drug, or missing data were imputed using non-responder imputation (NRI). |
| Arm/Group Title | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. |
| Measure Participants | 62 | 63 | 62 | 63 |
| Mean (Standard Deviation) [units on a scale] |
-1.62
(1.447)
|
-1.55
(1.182)
|
-1.24
(1.146)
|
-1.80
(1.453)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 5 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.863 |
| Comments | ||
| Method | Mixed-effects Model for Repeated Measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.53 to 0.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.25 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 10 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.503 |
| Comments | ||
| Method | Mixed-effects Model for Repeated Measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 0.65 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.25 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 30 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.289 |
| Comments | ||
| Method | Mixed-effects Model for Repeated Measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -0.77 to 0.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.25 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieve Low Disease Activity Using DAS28-hsCRP in Part B |
|---|---|
| Description | Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using VAS. DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug, for participants who completed or early discontinued dosing treatment period before the study was terminated in Part B. Missing values due to discontinuation of study or drug, or missing data were imputed using non-responder imputation (NRI). |
| Arm/Group Title | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. |
| Measure Participants | 54 | 56 | 52 | 55 |
| Number (95% Confidence Interval) [Percentage of Participants] |
27.8
308.9%
|
32.1
356.7%
|
21.2
212%
|
29.1
363.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 5 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.626 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 10 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.418 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 30 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.951 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Title | Percentage of Participants Who Achieve Clinical Remission Using DAS28-hsCRP in Part B |
|---|---|
| Description | Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (participant global VAS). DAS28 was calculated using following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Clinical remission is defined as DAS28-hsCRP <2.6. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug, for participants who completed or early discontinued dosing treatment period before the study was terminated in Part B. Missing values due to discontinuation of study or drug, or missing data were imputed using non-responder imputation (NRI). |
| Arm/Group Title | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 |
|---|---|---|---|---|
| Arm/Group Description | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. |
| Measure Participants | 54 | 56 | 52 | 55 |
| Number (95% Confidence Interval) [Percentage of Participants] |
20.4
226.7%
|
19.6
217.8%
|
7.7
77%
|
25.5
318.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 5 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.905 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 10 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.069 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Part A: Placebo, Part A: 30 mg LY3337641 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.547 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Title | Pharmacokinetics (PK): Clearance Parameter of LY3337641 |
|---|---|
| Description | Apparent total body clearance of drug after oral administration based on population PK analysis was evaluated. As prespecified per protocol, an overall population estimate of clearance is generated and data from Part A and B were combined for the analysis. The sparse data was then analyzed using population PK methods in Non linear Mixed Effects Model (NONMEM) to generate an overall population estimate of clearance. |
| Time Frame | Part A: Weeks 1, 2, and 4, Day 1 (0.5 to 2 hours postdose); Part B: Weeks 2, 4, 8, and 12, Day 1 (0.5 to 2 hours postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of the study drug and have evaluable PK data in in Part A and Part B. |
| Arm/Group Title | LY3337641 |
|---|---|
| Arm/Group Description | Participants received oral doses of 5 mg, 10 mg and 30 mg LY3337641 QD for 4 weeks in Part A and 12 weeks in Part B. |
| Measure Participants | 209 |
| Mean (Standard Error) [Liter per hour (L/hr)] |
29.1
(5.9)
|
Adverse Events
| Time Frame | Up to 88 Weeks | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All randomized participants who received at least 1 dose of the study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly. | |||||||||||||||||||||
| Arm/Group Title | Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 | Long-Term Extension: 5 mg LY3337641 | Long-Term Extension: 10 mg LY3337641 | Long-Term Extension: 30 mg LY3337641 | |||||||||||
| Arm/Group Description | Participants received oral dose of placebo once daily (QD) for 4 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 4 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 4 weeks. | Participants received oral dose of placebo QD for 12 weeks. | Participants received oral dose of 5 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 10 mg LY3337641 QD for 12 weeks. | Participants received oral dose of 30 mg LY3337641 QD for 12 weeks. | Participants who completed Part B of study received oral dose of 5 mg LY3337641 QD for an additional 52 weeks. | Participants who completed Part B of study received oral dose of 10 mg LY3337641 QD for an additional 52 weeks. | Participants who completed Part B of study received oral dose of 30 mg LY3337641 QD for an additional 52 weeks. | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 | Long-Term Extension: 5 mg LY3337641 | Long-Term Extension: 10 mg LY3337641 | Long-Term Extension: 30 mg LY3337641 | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/8 (0%) | 0/62 (0%) | 0/63 (0%) | 0/62 (0%) | 1/63 (1.6%) | 0/61 (0%) | 0/58 (0%) | 0/61 (0%) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 | Long-Term Extension: 5 mg LY3337641 | Long-Term Extension: 10 mg LY3337641 | Long-Term Extension: 30 mg LY3337641 | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | 0/10 (0%) | 0/8 (0%) | 2/62 (3.2%) | 0/63 (0%) | 0/62 (0%) | 3/63 (4.8%) | 1/61 (1.6%) | 3/58 (5.2%) | 1/61 (1.6%) | |||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||
| Cholecystitis acute | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/62 (1.6%) | 1 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||
| Pneumonia | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 1/61 (1.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Ankle fracture | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| Foot fracture | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Hand fracture | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| Joint dislocation | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/62 (1.6%) | 1 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Multiple injuries | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Patella fracture | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| Pubis fracture | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| Wrist fracture | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| Investigations | ||||||||||||||||||||||
| Alanine aminotransferase increased | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 1/61 (1.6%) | 1 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||
| Nephrolithiasis | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||
| Venous thrombosis | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| Part A: Placebo | Part A: 5 mg LY3337641 | Part A: 10 mg LY3337641 | Part A: 30 mg LY3337641 | Part B: Placebo | Part B: 5 mg LY3337641 | Part B: 10 mg LY3337641 | Part B: 30 mg LY3337641 | Long-Term Extension: 5 mg LY3337641 | Long-Term Extension: 10 mg LY3337641 | Long-Term Extension: 30 mg LY3337641 | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/9 (33.3%) | 1/9 (11.1%) | 6/10 (60%) | 2/8 (25%) | 7/62 (11.3%) | 10/63 (15.9%) | 12/62 (19.4%) | 19/63 (30.2%) | 11/61 (18%) | 12/58 (20.7%) | 10/61 (16.4%) | |||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||
| Constipation | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 1/62 (1.6%) | 1 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Diarrhoea | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 0/62 (0%) | 0 | 2/63 (3.2%) | 3 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Dry mouth | 0/9 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Nausea | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 1/62 (1.6%) | 2 | 1/63 (1.6%) | 1 | 1/61 (1.6%) | 1 | 1/58 (1.7%) | 1 | 0/61 (0%) | 0 |
| General disorders | ||||||||||||||||||||||
| Fatigue | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 4/63 (6.3%) | 4 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Non-cardiac chest pain | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||
| Bronchitis | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 2/63 (3.2%) | 2 | 1/61 (1.6%) | 1 | 3/58 (5.2%) | 4 | 1/61 (1.6%) | 1 |
| Laryngitis | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 1/61 (1.6%) | 1 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Nasopharyngitis | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 2/62 (3.2%) | 2 | 3/63 (4.8%) | 3 | 1/62 (1.6%) | 2 | 5/63 (7.9%) | 5 | 1/61 (1.6%) | 1 | 0/58 (0%) | 0 | 2/61 (3.3%) | 2 |
| Pharyngitis | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 2/62 (3.2%) | 3 | 0/63 (0%) | 0 | 1/62 (1.6%) | 1 | 3/63 (4.8%) | 4 | 0/61 (0%) | 0 | 2/58 (3.4%) | 2 | 1/61 (1.6%) | 1 |
| Sinusitis | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 1/62 (1.6%) | 1 | 1/63 (1.6%) | 1 | 0/61 (0%) | 0 | 2/58 (3.4%) | 2 | 2/61 (3.3%) | 2 |
| Urinary tract infection | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 1/62 (1.6%) | 1 | 1/63 (1.6%) | 1 | 2/61 (3.3%) | 2 | 3/58 (5.2%) | 4 | 4/61 (6.6%) | 4 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Hypertriglyceridaemia | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 1/62 (1.6%) | 1 | 0/63 (0%) | 0 | 1/61 (1.6%) | 1 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Hypokalaemia | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 2/63 (3.2%) | 2 | 0/61 (0%) | 0 | 1/58 (1.7%) | 2 | 0/61 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||
| Osteopenia | 0/9 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Rheumatoid arthritis | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 1/62 (1.6%) | 1 | 3/63 (4.8%) | 4 | 4/62 (6.5%) | 4 | 2/63 (3.2%) | 2 | 1/61 (1.6%) | 1 | 1/58 (1.7%) | 2 | 2/61 (3.3%) | 2 |
| Nervous system disorders | ||||||||||||||||||||||
| Carotid artery aneurysm | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Dizziness | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 0/8 (0%) | 0 | 0/62 (0%) | 0 | 0/63 (0%) | 0 | 1/62 (1.6%) | 1 | 0/63 (0%) | 0 | 1/61 (1.6%) | 1 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Headache | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 2/10 (20%) | 2 | 1/8 (12.5%) | 1 | 0/62 (0%) | 0 | 1/63 (1.6%) | 1 | 1/62 (1.6%) | 1 | 1/63 (1.6%) | 1 | 0/61 (0%) | 0 | 0/58 (0%) | 0 | 0/61 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||
| Benign prostatic hyperplasia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/10 (0%) | 0 | 0/6 (0%) | 0 | 0/10 (0%) | 0 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/10 (0%) | 0 |
| Erectile dysfunction | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/10 (0%) | 0 | 0/6 (0%) | 0 | 1/10 (10%) | 1 | 0/9 (0%) | 0 | 0/4 (0%) | 0 | 0/10 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||
| Cough | 0/9 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 | 1/62 (1.6%) | 1 | 0/63 (0%) | 0 | 1/62 (1.6%) | 1 | 1/63 (1.6%) | 1 | 2/61 (3.3%) | 2 | 1/58 (1.7%) | 1 | 2/61 (3.3%) | 2 |
Limitations/Caveats
The trial was terminated after an interim analysis of efficacy and safety data did not warrant continuation of the trial.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02628028
Other Study ID Numbers:
- 16173
- I8K-MC-JPDA
- 2015-003289-97
First Posted:
Dec 11, 2015
Last Update Posted:
Oct 9, 2019
Last Verified:
Sep 1, 2019