A Study for Patients With Active Rheumatoid Arthritis Despite Ongoing Methotrexate Therapy
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00785928
Collaborator
(none)
158
48
7
26
3.3
0.1
Study Details
Study Description
Brief Summary
To assess the efficacy of LY2127399 versus placebo using American College of Rheumatology (ACR)50 response scale at 24 weeks
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
158 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Phase 2, Dose-Ranging Study of Multiple Subcutaneous Doses of LY2127399 in Patients With Active Rheumatoid Arthritis Despite Ongoing Methotrexate Therapy
Study Start Date
:
Oct 1, 2008
Actual Primary Completion Date
:
Jan 1, 2010
Actual Study Completion Date
:
Dec 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Placebo
|
Drug: Placebo
Administered subcutaneously (SC) every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
| Experimental: 1 mg LY2127399
|
Biological: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
| Experimental: 3 mg LY2127399
|
Biological: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
| Experimental: 10 mg LY2127399
|
Biological: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
| Experimental: 30 mg LY2127399
|
Biological: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
| Experimental: 60 mg LY2127399
|
Biological: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
| Experimental: 120 mg LY2127399
|
Biological: LY2127399
Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20).
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 Response up to 24 Weeks [Up to week 24]
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR50 Responder is defined as a participant with >50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
Secondary Outcome Measures
- Percentage of Participants Achieving The American College of Rheumatology (ACR)20 Response up to 24 Weeks [Up to 24 weeks]
ACR20 Responder Index is composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR20 Responder is defined as participant with at least 20% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
- Change From Baseline in the Tender Joint Count up to 24 Weeks [Baseline, up to 24 weeks]
Number of tender and painful joints was determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were assessed by pressure and joint manipulation on physical examination. Participant was asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy.
- Change From Baseline in Swollen Joint Count up to 24 Weeks [Baseline, up to 24 weeks]
The number of swollen joints was determined by examination of 28 joints which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.
- Change From Baseline in the Disease Activity Score (DAS) up to 24 Weeks [Baseline, up to 24 weeks]
DAS (modified to include the 28 joint count [DAS28]) consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of his or her disease activity (participant global visual analog scale [pt global VAS]). The DAS28 is calculated by using the following formula: DAS28-CRP = 0.56*sqrt(28TJC) + 0.28*sqrt(28SJC) + 0.36*ln(CRP+1) + 0.014*pt global VAS + 0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
- Percentage of Participants With A European League Against Rheumatism Responder Index Based on the 28 Joint Count (EULAR28) up to 24 Weeks [Up to 24 weeks]
The EULAR28 categorizes clinical response based upon improvement since baseline in the Disease Activity Score (DAS) modified to include the 28 joint count (DAS28) and post-baseline DAS28 level. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (participant global visual analog scale [VAS]). EULAR28 categories include: No Response (improvement in DAS28 of less than or equal to 0.6 units or post-baseline DAS28 score greater than 5.1 with improvement by less than or equal to 1.2 units), Moderate Response (post-baseline DAS28 score less than or equal to 5.1 with improvement by more than 0.6 units but no greater than 1.2 units or post-baseline DAS28 score greater than 3.2 with improvement by more than 1.2 units), and Good Response (post-baseline DAS28 score less than or equal to 3.2 with improvement by more than 1.2 units).
- Change From Baseline in the Participant's Assessment of Joint Pain up to 24 Weeks [Baseline, up to 24 weeks]
Participant's assessment of joint pain using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
- Change From Baseline in the Participant's Assessment of Disease Activity up to 24 Weeks [Baseline, up to 24 weeks]
Participant's assessment of disease activity using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.
- Change From Baseline in the Physician's Assessment of Disease Activity up to 24 Weeks [Baseline, up to 24 weeks]
Physician's assessment of disease activity using a visual analog scale (VAS) that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.
- Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) up to 24 Weeks [Baseline, up to 24 weeks]
Participant's assessment of physical function. Disability section of questionnaire scores participant's self-perception on degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do) when dressing and grooming, arising, eating, walking, hygiene, reach, grip, and performing other daily activities. Scores for each of the functional areas were averaged to calculate the functional disability index. The HAQ-DI total score, which is the average of the nonmissing functional scores, ranges from 0 (no disability) to 3 (severe disability).
- Percent Change From Baseline in C-Reactive Protein (CRP) up to 24 Weeks [Baseline, up to 24 weeks]
Percent change = [(postbaseline CRP - baseline CRP)/baseline CRP]*100.
- Change From Baseline in the Functional Assessment of Chronic Illness (FACIT) Fatigue Scale up to 24 Weeks [Baseline, up to 24 weeks]
The FACIT Fatigue Scale is a brief participant-reported measure of fatigue and consists of 13 items. Scores range from 0 to 52, with higher scores indicating less fatigue.
- Change From Baseline in the Short Form Health Survey (SF-36) up to 24 Weeks [Baseline, up to 24 weeks]
A self-reported questionnaire that consists of 36 questions covering 8 health domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, and general health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The mental component summary (MCS) and the physical component summary (PCS) have been constructed based on the 8 SF-36 domains. MCS and PCS scores = 0 to 100 (higher scores indicate better health status).
- Pharmacokinetics of LY2127399: C-Trough Steady State Concentration at 24 Weeks [24 weeks]
C-trough is defined as the concentration of LY2127399 at the end of the dosing interval after the subcutaneous (sc) injection dosing once every 4 weeks. Mean C-trough value was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles.
- Pharmacokinetics of LY2127399: T-Half Life (t1/2, Tau) at 24 Weeks [24 weeks]
T1/2,tau is defined as the apparent steady state elimination within the dosing interval. T1/2,tau was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles.
- Change From Baseline in the Absolute Total B Cell (CD20+CD3- Cells) Count up to 24 Weeks [Baseline, up to 24 weeks]
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. Total B cell counts (CD20+CD3-) are represented by the number of cells per microliter (cells/µL). The reference range is 43 - 602 cells/µL.
- Change From Baseline in Serum Immunoglobulin up to 24 Weeks [Baseline, up to 24 weeks]
Serum immunoglobulin measured by Immunoglobulin G (IgG), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) levels.
- Number of Participants Experiencing An Adverse Event [Baseline up to 24 weeks]
Serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have given written informed consent
-
Women must not be at risk to become pregnant during study participation
-
Diagnosis of Rheumatoid Arthritis (RA)
-
Current, regular use of Methotrexate, at a stable dose
-
Other criteria to be reviewed by study doctor
Exclusion Criteria:
-
Use of excluded medications(reviewed by study doctor)
-
Have not failed biologic tumor necrosis factor-alpha (TNF-α) inhibitor therapy
-
Have had recent or ongoing infection which, in the opinion of the study doctor put patient at an unacceptable risk for participation in the study
-
Evidence of tuberculosis
-
Have systemic inflammatory condition other than RA, such as juvenile RA, Crohn's disease, ulcerative colitis, psoriatic arthritis or seronegative spondyloarthropathy
-
Other criteria to be reviewed by study doctor
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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. | Huntsville | Alabama | United States | 35801 |
| 2 | 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. | Calabasas | California | United States | 91302 |
| 3 | 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. | Upland | California | United States | 91786 |
| 4 | 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. | Vero Beach | Florida | United States | 32960 |
| 5 | 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. | Philadelphia | Pennsylvania | United States | 19152 |
| 6 | 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. | Dallas | Texas | United States | 75235 |
| 7 | 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 | C1417EYG | |
| 8 | 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. | Quilmes | Argentina | 1878 | |
| 9 | 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. | Brisbane | Queensland | Australia | 4066 |
| 10 | 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 | Queensland | Australia | 4558 |
| 11 | 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. | Elizabeth Vale | South Australia | Australia | 5112 |
| 12 | 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. | Santiago | Chile | ||
| 13 | 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. | Valdivia | Chile | ||
| 14 | 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. | Vina Del Mar | Chile | ||
| 15 | 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. | Leipzig | Germany | 04103 | |
| 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. | Budapest | Hungary | 1023 | |
| 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. | Esztergom | Hungary | 2500 | |
| 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. | Kistarcsa | Hungary | 2143 | |
| 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. | Szolnok | Hungary | 5000 | |
| 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. | Hyderabaad | India | 400082 | |
| 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. | Lucknow | India | 226018 | |
| 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. | Pune | India | 411001 | |
| 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. | Secunderabad | India | 800003 | |
| 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. | Chihuahua | Mexico | 31000 | |
| 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. | Cuernavaca | Mexico | 62270 | |
| 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. | Guadalajara | Mexico | 44100 | |
| 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. | Mexico City | Mexico | 06700 | |
| 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. | Monterrey | Mexico | 64020 | |
| 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. | San Luis Potosi | Mexico | 78210 | |
| 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. | Tampico | Mexico | 89000 | |
| 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. | Bialystok | Poland | 15-337 | |
| 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. | Chelm Slaski | Poland | 41-403 | |
| 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. | Elblag | Poland | 82-300 | |
| 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. | Krakow | Poland | 30-510 | |
| 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. | Lubin | Poland | 20-022 | |
| 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. | Lublin | Poland | 20-954 | |
| 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. | Poznan | Poland | 60-356 | |
| 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. | Torun | Poland | 87-100 | |
| 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. | Warsaw | Poland | 02-777 | |
| 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. | Wroclaw | Poland | 50-088 | |
| 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. | Brasov | Romania | 500365 | |
| 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. | Targu-Mures | Romania | 540136 | |
| 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. | Bratislava | Slovakia | 83103 | |
| 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. | Rimavska | Slovakia | 97101 | |
| 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. | Ivano-Frankivsk | Ukraine | 76018 | |
| 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. | Kiev | Ukraine | 1601 | |
| 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. | Odessa | Ukraine | 65027 | |
| 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. | Simferopol | Ukraine | 95017 |
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 - 5PM Eastern Time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00785928
Other Study ID Numbers:
- 12409
- H9B-MC-BCDH
First Posted:
Nov 5, 2008
Last Update Posted:
Jul 10, 2018
Last Verified:
Jun 1, 2018
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Participants received a total of 6 subcutaneous (SC) injections (Weeks 0, 4, 8, 12, 16, and 20) of either placebo or 1 of 6 LY2127399 doses (1, 3, 10, 30, 60, or 120 milligrams [mg]) during the Treatment Phase. The Follow-up Phase took place Weeks 24-44 and the B-cell Follow-up Phase took place Weeks 44-72. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Administered subcutaneously (SC) every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). |
| Period Title: Treatment Phase | |||||||
| STARTED | 36 | 30 | 20 | 15 | 18 | 13 | 26 |
| COMPLETED | 33 | 25 | 17 | 15 | 16 | 13 | 23 |
| NOT COMPLETED | 3 | 5 | 3 | 0 | 2 | 0 | 3 |
| Period Title: Treatment Phase | |||||||
| STARTED | 8 | 8 | 6 | 4 | 6 | 0 | 14 |
| COMPLETED | 7 | 5 | 4 | 4 | 4 | 0 | 9 |
| NOT COMPLETED | 1 | 3 | 2 | 0 | 2 | 0 | 5 |
Baseline Characteristics
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Administered subcutaneously (SC) every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Total of all reporting groups |
| Overall Participants | 36 | 30 | 20 | 15 | 18 | 13 | 26 | 158 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
50.6
(11.74)
|
54.6
(11.67)
|
53.4
(10.78)
|
51.2
(13.78)
|
54.5
(11.75)
|
44.4
(13.83)
|
50.7
(12.02)
|
51.7
(12.13)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
30
83.3%
|
26
86.7%
|
14
70%
|
12
80%
|
15
83.3%
|
12
92.3%
|
18
69.2%
|
127
80.4%
|
| Male |
6
16.7%
|
4
13.3%
|
6
30%
|
3
20%
|
3
16.7%
|
1
7.7%
|
8
30.8%
|
31
19.6%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||
| Caucasian |
25
69.4%
|
22
73.3%
|
13
65%
|
8
53.3%
|
11
61.1%
|
5
38.5%
|
17
65.4%
|
101
63.9%
|
| African |
1
2.8%
|
1
3.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
1.3%
|
| Hispanic |
8
22.2%
|
5
16.7%
|
6
30%
|
6
40%
|
6
33.3%
|
5
38.5%
|
8
30.8%
|
44
27.8%
|
| East Asian |
2
5.6%
|
2
6.7%
|
1
5%
|
0
0%
|
1
5.6%
|
3
23.1%
|
1
3.8%
|
10
6.3%
|
| West Asian |
0
0%
|
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
1
0.6%
|
| Region of Enrollment (Count of Participants) | ||||||||
| Argentina |
1
2.8%
|
0
0%
|
0
0%
|
2
13.3%
|
1
5.6%
|
0
0%
|
1
3.8%
|
5
3.2%
|
| Australia |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
1
5.6%
|
0
0%
|
1
3.8%
|
3
1.9%
|
| Chile |
4
11.1%
|
2
6.7%
|
2
10%
|
2
13.3%
|
3
16.7%
|
2
15.4%
|
2
7.7%
|
17
10.8%
|
| Germany |
1
2.8%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.6%
|
| Hungary |
4
11.1%
|
2
6.7%
|
3
15%
|
2
13.3%
|
2
11.1%
|
0
0%
|
1
3.8%
|
14
8.9%
|
| India |
2
5.6%
|
2
6.7%
|
1
5%
|
0
0%
|
1
5.6%
|
3
23.1%
|
1
3.8%
|
10
6.3%
|
| Mexico |
5
13.9%
|
4
13.3%
|
4
20%
|
2
13.3%
|
3
16.7%
|
3
23.1%
|
4
15.4%
|
25
15.8%
|
| Poland |
12
33.3%
|
8
26.7%
|
5
25%
|
4
26.7%
|
4
22.2%
|
2
15.4%
|
5
19.2%
|
40
25.3%
|
| Romania |
1
2.8%
|
1
3.3%
|
1
5%
|
0
0%
|
1
5.6%
|
1
7.7%
|
1
3.8%
|
6
3.8%
|
| Slovakia |
0
0%
|
1
3.3%
|
1
5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
1.3%
|
| Ukraine |
5
13.9%
|
3
10%
|
3
15%
|
2
13.3%
|
2
11.1%
|
0
0%
|
8
30.8%
|
23
14.6%
|
| United States |
1
2.8%
|
6
20%
|
0
0%
|
1
6.7%
|
0
0%
|
2
15.4%
|
2
7.7%
|
12
7.6%
|
Outcome Measures
| Title | Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 Response up to 24 Weeks |
|---|---|
| Description | ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR50 Responder is defined as a participant with >50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. |
| Time Frame | Up to week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). Two participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Administered subcutaneously (SC) every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). | Administered SC every 4 weeks over a 24-week period (Weeks 0, 4, 8, 12, 16, and 20). |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Number [percentage of participants] |
18.1
50.3%
|
17.7
59%
|
17.0
85%
|
15.0
100%
|
11.8
65.6%
|
11.8
90.8%
|
37.0
142.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399, 3 mg LY2127399, 10 mg LY2127399, 30 mg LY2127399, 60 mg LY2127399, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.059 |
| Comments | This is p-value for the fitted ACR50 response rate and is based on the dose-response regression model and comes from the joint test of linear and quadratic dose response (response=dose+dose^2) from the likelihood ratio test. | |
| Method | Linear-quadratic regression model | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399, 3 mg LY2127399, 10 mg LY2127399, 30 mg LY2127399, 60 mg LY2127399, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.042 |
| Comments | This is the p-value for the estimated dose level of the smallest dose, in milligrams (mg), that achieves at least 95% of the maximal efficacy (ED95) and is based on the comparisons that the ED95 yields a higher fitted response rate than placebo. | |
| Method | Linear-quadratic regression model | |
| Comments | This is ED95 in mg. | |
| Method of Estimation | Estimation Parameter | ED95 |
| Estimated Value | 119.0 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving The American College of Rheumatology (ACR)20 Response up to 24 Weeks |
|---|---|
| Description | ACR20 Responder Index is composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR20 Responder is defined as participant with at least 20% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF)/non-responder imputation (NRI). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Number [percentage of participants] |
43.2
120%
|
43.6
145.3%
|
44.3
221.5%
|
46.9
312.7%
|
53.5
297.2%
|
61.5
473.1%
|
70.1
269.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399, 3 mg LY2127399, 10 mg LY2127399, 30 mg LY2127399, 60 mg LY2127399, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.044 |
| Comments | This is the p-value for the fitted ACR20 response rate and is based on the dose-response regression model and comes from the joint test of linear and quadratic dose response (response=dose+dose^2) from the likelihood ratio test. | |
| Method | Linear-quadratic regression model | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399, 3 mg LY2127399, 10 mg LY2127399, 30 mg LY2127399, 60 mg LY2127399, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | This p-value is for estimated dose level of the smallest dose, in milligrams (mg), that achieves at least 95% of the maximal efficacy (ED95) of the ACR20 and is based on the comparisons that the ED95 yields a higher fitted response rate than placebo. | |
| Method | Linear-quadratic regression model | |
| Comments | This is the ED95 in mg. | |
| Method of Estimation | Estimation Parameter | ED95 |
| Estimated Value | 118.5 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in the Tender Joint Count up to 24 Weeks |
|---|---|
| Description | Number of tender and painful joints was determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were assessed by pressure and joint manipulation on physical examination. Participant was asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [tender joints] |
-7.1
(8.21)
|
-7.3
(10.24)
|
-4.5
(7.74)
|
-8.7
(5.94)
|
-7.8
(7.68)
|
-7.4
(10.22)
|
-8.2
(6.41)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.623 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2127399 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.160 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2127399 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.568 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2127399 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.633 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2127399 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.754 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2127399 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.289 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2127399 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Swollen Joint Count up to 24 Weeks |
|---|---|
| Description | The number of swollen joints was determined by examination of 28 joints which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [swollen joints] |
-5.6
(5.66)
|
-6.9
(6.10)
|
-5.7
(5.57)
|
-8.9
(6.03)
|
-5.4
(4.34)
|
-6.2
(6.19)
|
-7.3
(5.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.671 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.696 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.367 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.645 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.944 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.133 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in the Disease Activity Score (DAS) up to 24 Weeks |
|---|---|
| Description | DAS (modified to include the 28 joint count [DAS28]) consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of his or her disease activity (participant global visual analog scale [pt global VAS]). The DAS28 is calculated by using the following formula: DAS28-CRP = 0.56*sqrt(28TJC) + 0.28*sqrt(28SJC) + 0.36*ln(CRP+1) + 0.014*pt global VAS + 0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 35 | 28 | 19 | 14 | 17 | 12 | 23 |
| Mean (Standard Deviation) [units on a scale] |
-1.448
(1.310)
|
-1.539
(1.346)
|
-1.026
(1.118)
|
-1.678
(0.987)
|
-1.536
(1.257)
|
-1.642
(1.222)
|
-1.915
(1.183)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.457 |
| Comments | Pairwise comparison (1-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.874 |
| Comments | Pairwise comparison (1-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.278 |
| Comments | Pairwise comparison (1-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.357 |
| Comments | Pairwise comparison (1-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.271 |
| Comments | Pairwise comparison (1-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.048 |
| Comments | Pairwise comparison (1-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Percentage of Participants With A European League Against Rheumatism Responder Index Based on the 28 Joint Count (EULAR28) up to 24 Weeks |
|---|---|
| Description | The EULAR28 categorizes clinical response based upon improvement since baseline in the Disease Activity Score (DAS) modified to include the 28 joint count (DAS28) and post-baseline DAS28 level. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (participant global visual analog scale [VAS]). EULAR28 categories include: No Response (improvement in DAS28 of less than or equal to 0.6 units or post-baseline DAS28 score greater than 5.1 with improvement by less than or equal to 1.2 units), Moderate Response (post-baseline DAS28 score less than or equal to 5.1 with improvement by more than 0.6 units but no greater than 1.2 units or post-baseline DAS28 score greater than 3.2 with improvement by more than 1.2 units), and Good Response (post-baseline DAS28 score less than or equal to 3.2 with improvement by more than 1.2 units). |
| Time Frame | Up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Good response |
11.4
31.7%
|
10.7
35.7%
|
10.5
52.5%
|
7.1
47.3%
|
23.5
130.6%
|
25.0
192.3%
|
26.1
100.4%
|
| Moderate response |
45.7
126.9%
|
53.6
178.7%
|
42.1
210.5%
|
50.0
333.3%
|
52.9
293.9%
|
33.3
256.2%
|
56.5
217.3%
|
| No response |
42.9
119.2%
|
35.7
119%
|
47.4
237%
|
42.9
286%
|
23.5
130.6%
|
41.7
320.8%
|
17.4
66.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.875 |
| Comments | This p-value is from 2-sided comparison of 1 mg LY2127399 versus placebo using Fisher's exact test for the 3 levels of EULAR response (good, moderate, no). | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | This p-value is from 2-sided comparison of 3 mg LY2127399 versus placebo using Fisher's exact test for the 3 levels of EULAR response (good, moderate, no). | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | This p-value is from 2-sided comparison of 10 mg LY2127399 versus placebo using Fisher's exact test for the 3 levels of EULAR response (good, moderate, no). | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.304 |
| Comments | This p-value is from a 2-sided comparison of 30 mg LY2127399 versus placebo using a Chi-square test for the 3 levels of EULAR response (good, moderate, no). | |
| Method | Chi-squared | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.489 |
| Comments | This p-value is from a 2-sided comparison of 60 mg LY2127399 versus placebo using a Chi-square test for the 3 levels of EULAR response (good, moderate, no). | |
| Method | Chi-squared | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.091 |
| Comments | This p-value is from a 2-sided comparison of 120 mg LY2127399 versus placebo using a Chi-square test for the 3 levels of EULAR response (good, moderate, no). | |
| Method | Chi-squared | |
| Comments | ||
| Title | Change From Baseline in the Participant's Assessment of Joint Pain up to 24 Weeks |
|---|---|
| Description | Participant's assessment of joint pain using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no pain and 100 indicated worst possible pain. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [millimeters (mm)] |
-19.5
(27.50)
|
-17.8
(23.40)
|
-12.8
(19.76)
|
-21.2
(25.42)
|
-13.1
(21.95)
|
-17.6
(14.20)
|
-30.3
(25.93)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.746 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.393 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.549 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.619 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.893 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.066 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in the Participant's Assessment of Disease Activity up to 24 Weeks |
|---|---|
| Description | Participant's assessment of disease activity using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 35 | 28 | 19 | 15 | 17 | 13 | 24 |
| Mean (Standard Deviation) [millimeters (mm)] |
-23.7
(24.76)
|
-21.2
(24.63)
|
-16.1
(18.58)
|
-22.5
(28.56)
|
-19.3
(17.58)
|
-15.5
(19.65)
|
-33.9
(22.68)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.583 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.311 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.752 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.737 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.522 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.073 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in the Physician's Assessment of Disease Activity up to 24 Weeks |
|---|---|
| Description | Physician's assessment of disease activity using a visual analog scale (VAS) that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [millimeters (mm)] |
-22.8
(22.02)
|
-22.8
(20.26)
|
-26.3
(26.09)
|
-30.2
(22.15)
|
-28.3
(20.62)
|
-21.4
(15.96)
|
-36.1
(17.06)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.969 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.352 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.406 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.266 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.708 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) up to 24 Weeks |
|---|---|
| Description | Participant's assessment of physical function. Disability section of questionnaire scores participant's self-perception on degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do) when dressing and grooming, arising, eating, walking, hygiene, reach, grip, and performing other daily activities. Scores for each of the functional areas were averaged to calculate the functional disability index. The HAQ-DI total score, which is the average of the nonmissing functional scores, ranges from 0 (no disability) to 3 (severe disability). |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [units on a scale] |
-0.281
(0.481)
|
-0.288
(0.609)
|
-0.206
(0.406)
|
-0.258
(0.373)
|
-0.292
(0.554)
|
-0.587
(0.546)
|
-0.370
(0.426)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.880 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.575 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.992 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.646 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.054 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.472 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Percent Change From Baseline in C-Reactive Protein (CRP) up to 24 Weeks |
|---|---|
| Description | Percent change = [(postbaseline CRP - baseline CRP)/baseline CRP]*100. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [percent change] |
9.13
(136.683)
|
18.28
(92.909)
|
93.75
(265.331)
|
5.60
(73.212)
|
24.17
(188.146)
|
-34.42
(46.632)
|
7.50
(132.313)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.952 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable, treatment as the fixed factor, and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.085 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable, treatment as the fixed factor, and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.143 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable, treatment as the fixed factor, and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.242 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable, treatment as the fixed factor, and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.317 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable, treatment as the fixed factor, and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.456 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable, treatment as the fixed factor, and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in the Functional Assessment of Chronic Illness (FACIT) Fatigue Scale up to 24 Weeks |
|---|---|
| Description | The FACIT Fatigue Scale is a brief participant-reported measure of fatigue and consists of 13 items. Scores range from 0 to 52, with higher scores indicating less fatigue. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| Mean (Standard Deviation) [units on a scale] |
4.4
(12.22)
|
3.9
(10.95)
|
3.8
(8.04)
|
8.1
(8.77)
|
6.9
(8.08)
|
8.0
(8.19)
|
9.6
(7.83)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.833 |
| Comments | Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.826 |
| Comments | Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.091 |
| Comments | Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.127 |
| Comments | Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.243 |
| Comments | Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and the baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in the Short Form Health Survey (SF-36) up to 24 Weeks |
|---|---|
| Description | A self-reported questionnaire that consists of 36 questions covering 8 health domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, and general health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The mental component summary (MCS) and the physical component summary (PCS) have been constructed based on the 8 SF-36 domains. MCS and PCS scores = 0 to 100 (higher scores indicate better health status). |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 17 | 13 | 24 |
| Physical Health Component |
4.284
(7.889)
|
3.422
(7.592)
|
2.534
(4.779)
|
5.584
(7.905)
|
3.680
(5.289)
|
9.487
(8.366)
|
4.053
(6.353)
|
| Mental Health Component |
3.623
(10.414)
|
2.899
(13.094)
|
4.263
(11.304)
|
5.223
(11.289)
|
4.166
(7.733)
|
6.266
(7.139)
|
9.198
(9.822)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.562 |
| Comments | P-value for physical health component. Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.539 |
| Comments | P-value for physical health component. Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.304 |
| Comments | P-value for physical health component. Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.832 |
| Comments | P-value for physical health component. Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.010 |
| Comments | P-value for physical health component. Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.980 |
| Comments | P-value for physical health component. Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.569 |
| Comments | P-value for mental health component. Pairwise comparison (2-sided) of 1 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.953 |
| Comments | P-value for mental health component. Pairwise comparison (2-sided) of 3 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.647 |
| Comments | P-value for mental health component. Pairwise comparison (2-sided) of 10 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.507 |
| Comments | P-value for mental health component. Pairwise comparison (2-sided) of 30 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.821 |
| Comments | P-value for mental health component. Pairwise comparison (2-sided) of 60 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.045 |
| Comments | P-value for mental health component. Pairwise comparison (2-sided) of 120 mg LY2123799 versus placebo using contrast statements within an analysis of covariance (ANCOVA) model with treatment as the fixed factor and baseline value as the covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Pharmacokinetics of LY2127399: C-Trough Steady State Concentration at 24 Weeks |
|---|---|
| Description | C-trough is defined as the concentration of LY2127399 at the end of the dosing interval after the subcutaneous (sc) injection dosing once every 4 weeks. Mean C-trough value was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis population included all intent-to-treat (ITT) participants who received LY2127399 and who had evaluable PK data except 2 participants who were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg of LY2127399 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 1 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 30 | 20 | 15 | 18 | 13 | 24 |
| Number [micrograms per milliliter (µg/mL)] |
0.0100
|
0.0400
|
0.270
|
1.94
|
5.16
|
11.9
|
| Title | Pharmacokinetics of LY2127399: T-Half Life (t1/2, Tau) at 24 Weeks |
|---|---|
| Description | T1/2,tau is defined as the apparent steady state elimination within the dosing interval. T1/2,tau was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis population included all intent-to-treat (ITT) participants who received LY2127399 and who had evaluable PK data except 2 participants who were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 1 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 30 | 20 | 15 | 18 | 13 | 24 |
| Number [days] |
7.07
|
7.94
|
9.76
|
15.9
|
19.5
|
21.6
|
| Title | Change From Baseline in the Absolute Total B Cell (CD20+CD3- Cells) Count up to 24 Weeks |
|---|---|
| Description | B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. Total B cell counts (CD20+CD3-) are represented by the number of cells per microliter (cells/µL). The reference range is 43 - 602 cells/µL. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 35 | 30 | 20 | 15 | 17 | 13 | 24 |
| Mean (Standard Deviation) [cells per microliter (cells/µL)] |
17.63
(75.880)
|
-18.77
(96.410)
|
-50.85
(130.405)
|
-36.87
(71.287)
|
-68.59
(115.971)
|
-11.15
(111.577)
|
-27.88
(97.729)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.236 |
| Comments | Pairwise (2-sided) comparisons of 1 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable treatment as the fixed factor and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | Pairwise (2-sided) comparisons of 3 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable treatment as the fixed factor and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | Pairwise (2-sided) comparisons of 10 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable treatment as the fixed factor and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | Pairwise (2-sided) comparisons of 30 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable treatment as the fixed factor and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.734 |
| Comments | Pairwise (2-sided) comparisons of 60 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable treatment as the fixed factor and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | Pairwise (2-sided) comparisons of 120 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with the standardized rank outcome variable treatment as the fixed factor and the standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Serum Immunoglobulin up to 24 Weeks |
|---|---|
| Description | Serum immunoglobulin measured by Immunoglobulin G (IgG), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) levels. |
| Time Frame | Baseline, up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 24 |
| IgG |
-0.12
(2.964)
|
-0.14
(1.986)
|
-0.45
(3.179)
|
-0.45
(2.303)
|
-1.06
(2.650)
|
-0.93
(1.381)
|
-0.37
(2.147)
|
| IgM |
0.02
(0.323)
|
0.07
(0.336)
|
-0.02
(0.269)
|
-0.11
(0.283)
|
-0.08
(0.531)
|
-0.30
(0.299)
|
-0.09
(0.384)
|
| IgA |
-0.12
(0.482)
|
-0.09
(0.583)
|
-0.24
(0.712)
|
-0.53
(0.679)
|
-0.58
(0.977)
|
-0.42
(0.453)
|
-0.25
(0.631)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.901 |
| Comments | P-value for IgG. Pairwise comparison (2-sided) of 1 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.840 |
| Comments | P-value for IgG. Pairwise comparison (2-sided) of 3 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.882 |
| Comments | P-value for IgG. Pairwise comparison (2-sided) of 10 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.225 |
| Comments | P-value for IgG. Pairwise comparison (2-sided) of 30 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.340 |
| Comments | P-value for IgG. Pairwise comparison (2-sided) of 60 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.850 |
| Comments | P-value for IgG. Pairwise comparison (2-sided) of 120 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.447 |
| Comments | P-value for IgM. Pairwise comparison (2-sided) of 1 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.909 |
| Comments | P-value for IgM. Pairwise comparison (2-sided) of 3 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.152 |
| Comments | P-value for IgM. Pairwise comparison (2-sided) of 10 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.023 |
| Comments | P-value for IgM. Pairwise comparison (2-sided) of 30 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | P-value for IgM. Pairwise comparison (2-sided) of 60 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | P-value for IgM. Pairwise comparison (2-sided) of 120 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 1 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.944 |
| Comments | P-value for IgA. Pairwise comparison (2-sided) of 1 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 3 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.677 |
| Comments | P-value for IgA. Pairwise comparison (2-sided) of 3 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 10 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.053 |
| Comments | P-value for IgA. Pairwise comparison (2-sided) of 10 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.061 |
| Comments | P-value for IgA. Pairwise comparison (2-sided) of 30 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 60 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | P-value for IgA. Pairwise comparison (2-sided) of 60 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as the fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 120 mg LY2127399 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.030 |
| Comments | P-value for IgA. Pairwise comparison (2-sided) of 120 mg LY2127399 versus placebo using ranked analysis of covariance (ANCOVA) with standardized rank outcome variable, treatment as fixed factor, and standardized rank baseline value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Title | Number of Participants Experiencing An Adverse Event |
|---|---|
| Description | Serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section. |
| Time Frame | Baseline up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received any amount of blinded study drug. |
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. |
| Measure Participants | 36 | 30 | 20 | 15 | 18 | 13 | 26 |
| Serious Adverse Events |
5
13.9%
|
4
13.3%
|
0
0%
|
0
0%
|
3
16.7%
|
2
15.4%
|
1
3.8%
|
| Other Nonserious Adverse Events |
21
58.3%
|
19
63.3%
|
12
60%
|
9
60%
|
11
61.1%
|
8
61.5%
|
13
50%
|
Adverse Events
| Time Frame | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||
| Arm/Group Title | Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 | Placebo - Follow-up Period | 1 mg LY2127399 - Follow-up Period | 3 mg LY2127399 - Follow-up Period | 10 mg LY2127399 - Follow-up Period | 30 mg LY2127399 - Follow-up Period | 60 mg LY2127399 - Follow-up Period | 120 mg LY2127399 - Follow-up Period | ||||||||||||||
| Arm/Group Description | Placebo was administered subcutaneously (SC) every 4 weeks over a 24-week period. | 1 milligram (mg) of LY2127399 was administered SC every 4 weeks over a 24-week period. | 3 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 10 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 30 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 60 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | 120 mg of LY2127399 was administered SC every 4 weeks over a 24-week period. | Participants were assessed but did not receive any study medication during the follow-up period. | Participants were assessed but did not receive any study medication during the follow-up period. | Participants were assessed but did not receive any study medication during the follow-up period. | Participants were assessed but did not receive any study medication during the follow-up period. | Participants were assessed but did not receive any study medication during the follow-up period. | Participants were assessed but did not receive any study medication during the follow-up period. | Participants were assessed but did not receive any study medication during the follow-up period. | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 | Placebo - Follow-up Period | 1 mg LY2127399 - Follow-up Period | 3 mg LY2127399 - Follow-up Period | 10 mg LY2127399 - Follow-up Period | 30 mg LY2127399 - Follow-up Period | 60 mg LY2127399 - Follow-up Period | 120 mg LY2127399 - Follow-up Period | |||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||
| Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 | Placebo - Follow-up Period | 1 mg LY2127399 - Follow-up Period | 3 mg LY2127399 - Follow-up Period | 10 mg LY2127399 - Follow-up Period | 30 mg LY2127399 - Follow-up Period | 60 mg LY2127399 - Follow-up Period | 120 mg LY2127399 - Follow-up Period | |||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/36 (13.9%) | 4/30 (13.3%) | 0/20 (0%) | 0/15 (0%) | 3/18 (16.7%) | 2/13 (15.4%) | 1/26 (3.8%) | 0/8 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/4 (0%) | 1/6 (16.7%) | 0/0 (NaN) | 0/14 (0%) | ||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||
| Atrial flutter | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Colitis | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Intestinal obstruction | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Chest pain | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Bile duct stone | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Cholecystitis acute | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||
| Diverticulitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Lung infection | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Pneumonia influenzal | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Pyelonephritis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Sepsis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Rheumatoid arthritis | 2/36 (5.6%) | 2 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||
| Dizziness | 0/36 (0%) | 0 | 1/30 (3.3%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hemiplegia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Nephrolithiasis | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Renal failure | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Ovarian cyst | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Postmenopausal haemorrhage | 1/36 (2.8%) | 2 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Respiratory failure | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
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| Placebo | 1 mg LY2127399 | 3 mg LY2127399 | 10 mg LY2127399 | 30 mg LY2127399 | 60 mg LY2127399 | 120 mg LY2127399 | Placebo - Follow-up Period | 1 mg LY2127399 - Follow-up Period | 3 mg LY2127399 - Follow-up Period | 10 mg LY2127399 - Follow-up Period | 30 mg LY2127399 - Follow-up Period | 60 mg LY2127399 - Follow-up Period | 120 mg LY2127399 - Follow-up Period | |||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/36 (58.3%) | 19/30 (63.3%) | 12/20 (60%) | 9/15 (60%) | 11/18 (61.1%) | 8/13 (61.5%) | 13/26 (50%) | 1/8 (12.5%) | 2/8 (25%) | 1/6 (16.7%) | 3/4 (75%) | 3/6 (50%) | 0/0 (NaN) | 1/14 (7.1%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Eosinophilia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Leukocytosis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Leukopenia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Microcytic anaemia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Thrombocytosis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||
| Bradycardia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Myocardial ischaemia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Sinus bradycardia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Deafness | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Vertigo | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||||||
| Foreign body sensation in eyes | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Lacrimation increased | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal distension | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Abdominal pain lower | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Abdominal pain upper | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Constipation | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Diarrhoea | 2/36 (5.6%) | 2 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Flatulence | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Food poisoning | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gastritis | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Nausea | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 1/14 (7.1%) | 2 |
| Periodontitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Toothache | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||||
| Chills | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Fatigue | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Injection site erythema | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Injection site pain | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 4/15 (26.7%) | 4 | 1/18 (5.6%) | 1 | 1/13 (7.7%) | 1 | 2/26 (7.7%) | 2 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Injection site pruritus | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Non-cardiac chest pain | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Oedema | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Pyrexia | 1/36 (2.8%) | 1 | 2/30 (6.7%) | 2 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Hepatotoxicity | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||||||
| Allergy to arthropod bite | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||
| Abscess neck | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Acute sinusitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Bronchitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 2/13 (15.4%) | 2 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Cellulitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Diverticulitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Furuncle | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gastroenteritis | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gastroenteritis viral | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gingival abscess | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| H1n1 influenza | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Herpes zoster | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Impetigo | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Influenza | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Laryngitis viral | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Nasopharyngitis | 2/36 (5.6%) | 2 | 2/30 (6.7%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 2/18 (11.1%) | 2 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Oral fungal infection | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Oral herpes | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Pharyngitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Respiratory tract infection | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 2/20 (10%) | 2 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Tinea versicolour | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Trichophytic granuloma | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Upper respiratory tract infection | 1/36 (2.8%) | 1 | 3/30 (10%) | 3 | 0/20 (0%) | 0 | 3/15 (20%) | 3 | 0/18 (0%) | 0 | 2/13 (15.4%) | 2 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Urinary tract infection | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Viral upper respiratory tract infection | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Contusion | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Fall | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Joint injury | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Joint sprain | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Traumatic haematoma | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Aspartate aminotransferase increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Body temperature increased | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Electrocardiogram qt interval abnormal | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Electrocardiogram qt prolonged | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Electrocardiogram t wave abnormal | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Gamma-glutamyltransferase increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hepatic enzyme increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Neutrophil count increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Platelet count increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Red blood cell sedimentation rate increased | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Transaminases increased | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Weight decreased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Weight increased | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| White blood cell count increased | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Diabetes mellitus | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hypokalaemia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Back pain | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Bone pain | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Muscle spasms | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Musculoskeletal pain | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Myalgia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Osteoarthritis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Rheumatoid arthritis | 5/36 (13.9%) | 5 | 3/30 (10%) | 5 | 2/20 (10%) | 2 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 2 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||
| Diabetic neuropathy | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Headache | 2/36 (5.6%) | 2 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hypoaesthesia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Intercostal neuralgia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Neuralgia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Paraesthesia | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 2 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Somnolence | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 2 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Trigeminal neuralgia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 1/8 (12.5%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Depression | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Insomnia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Erectile dysfunction | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Menorrhagia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Postmenopausal haemorrhage | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 1/13 (7.7%) | 1 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Cough | 1/36 (2.8%) | 1 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 1/15 (6.7%) | 2 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Oropharyngeal pain | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Pneumonitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Productive cough | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Upper respiratory tract congestion | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Alopecia | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Cutaneous vasculitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Dermatitis | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Dyshidrosis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Erythema | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Hyperhidrosis | 1/36 (2.8%) | 1 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Rash | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 1/18 (5.6%) | 2 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Skin plaque | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Stasis dermatitis | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 1/26 (3.8%) | 1 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Surgical and medical procedures | ||||||||||||||||||||||||||||
| Cervical diathermy | 0/36 (0%) | 0 | 0/30 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 0/18 (0%) | 0 | 0/13 (0%) | 0 | 0/26 (0%) | 0 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||
| Hypertension | 0/36 (0%) | 0 | 1/30 (3.3%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 | 1/18 (5.6%) | 1 | 0/13 (0%) | 0 | 2/26 (7.7%) | 2 | 0/8 (0%) | 0 | 0/8 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/0 (NaN) | 0 | 0/14 (0%) | 0 |
Limitations/Caveats
[Not Specified]
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 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00785928
Other Study ID Numbers:
- 12409
- H9B-MC-BCDH
First Posted:
Nov 5, 2008
Last Update Posted:
Jul 10, 2018
Last Verified:
Jun 1, 2018