A Study of LY2541546 in Women With Low Bone Mineral Density

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01144377
• Collaborator: (none)
• Enrollment: 154
• Locations: 8
• Arms: 5
• Duration (Months): 30.1
• Patients Per Site: 19.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary objectives of this study include evaluating the dose response of LY2541546 using bone mineral density (BMD) change from baseline as compared to placebo and evaluating the overall safety and tolerability of LY2541546 following multiple subcutaneous administrations in postmenopausal (PMP) women with low BMD. Following the last dose of study drug, participants will be able to participate in a 12 month extension to collect additional safety and efficacy data (no further treatment will be administered during this extension).

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: LY2541546; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Randomized Study of LY2541546 Versus Placebo in Postmenopausal Women With Low Bone Mineral Density: An Evaluation of the Dose Response Relationship Using Bone Mineral Density
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 180 mg LY2541546 Q4W + Placebo LY2541546: 180 milligrams (mg) administered subcutaneously every 4 weeks (Q4W) for 52 weeks. Placebo: administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	Drug: LY2541546; Administered subcutaneously; Other Names: Blosozumab ; Drug: Placebo; Administered subcutaneously
Experimental: 180 mg LY2541546 Q2W LY2541546: 180 milligrams (mg) administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	Drug: LY2541546; Administered subcutaneously; Other Names: Blosozumab
Experimental: 270 mg LY2541546 Q2W LY2541546: 270 milligrams (mg) LY2541546 administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	Drug: LY2541546; Administered subcutaneously; Other Names: Blosozumab
Experimental: 270 mg LY2541546 Q12W + Placebo LY2541546: 270 milligrams (mg) administered subcutaneously every 12 weeks (Q12W) for 52 weeks. Placebo: administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	Drug: LY2541546; Administered subcutaneously; Other Names: Blosozumab ; Drug: Placebo; Administered subcutaneously
Placebo Comparator: Placebo Comparator Q2W Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	Drug: Placebo; Administered subcutaneously

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD) [Baseline, 52 weeks]

   Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate.

Secondary Outcome Measures

1. Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD) [Baseline, 12 weeks and 24 weeks and 64 weeks]

   Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate

2. Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD) [Baseline, 24 weeks and 52 weeks and 64 weeks]

   Femoral neck and total hip bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline BMD as a covariate.

3. Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD) [Baseline, 52 weeks]

   Total radius of the wrist bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a 1-factor analysis of covariance model with treatment group as the main effect and baseline BMD as a covariate.

4. Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP) [Baseline, 52 weeks]

5. Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx) [Baseline, 52 weeks]

6. Change From Baseline to 52 Week Endpoint in Osteocalcin [Baseline, 52 weeks]

7. Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP) [Baseline, 52 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory, postmenopausal women, inclusive.

• Have low bone mineral density (BMD), defined as a T-score or equivalent BMD absolute value (grams/square centimeter [g/cm^2]) for the lumbar spine of between -3.5 and -2.0, inclusive.

• Without language barrier, reliable, and willing to make themselves available for the duration of the study and to follow study procedures.

• Willing to take study drug and daily supplements (calcium and Vitamin D).

• Normal laboratory tests or laboratory test results determined not clinically significant by the investigator. Serum phosphate and serum calcium must be within normal limits, and platelet level greater than 100,000 cubic millimeters (mm^3).

Exclusion Criteria:

• Have received treatment with any of the following medications more recently than 3 months prior to screening Androgen, Calcitonin, Estrogen (including over the counter preparations known to have estrogenic activity), Progestin (including over the counter preparations known to have progestogenic activity), selective estrogen receptor modulators (SERMs) (Raloxifene, Tamoxifen, Toremifene, Clomiphene), or Tibolone.

• Have previously used or currently use denosumab, parathyroid hormone (PTH) and/or PTH analogs, strontium ranelate, or parenteral formulations of bisphosphonates.

• Have received treatment with any oral bisphosphonate within the last year.

• Have received therapeutic doses of systemic corticosteroids for more than one month during the 6 months prior to screening.

• Have received therapeutic doses of fluorides (20 milligrams per day) for more than 3 months during the last 3 years, or for more than a total of 2 years, or any within the last 6 months.

• Have severe Vitamin D deficiency defined as 25-hydroxyvitamin D less than <9.2 nanograms per milliliter (ng/mL) [23 nanomoles per liter (nmol/L)] at screening. If the serum 25-hydroxy-vitamin D level at screening is less than or equal to 9.2 ng/mL and <20 ng/mL, participants will receive a loading dose of Vitamin D (at a dose of approximately 100,000 international units (IU) given orally) prior to enrollment.

• Have any known bone disorder other than low BMD or osteoporosis.

• Have a history of osteoporotic fractures, including known prevalent vertebral fracture or evidence of prevalent vertebral fracture on screening spine X-ray or dual-energy x-ray absorptiometry (DXA), or are considered to be at high risk for fracture.

• Presence of any abnormality (such as artifacts or osteophytes) that would confound DXA evaluation of lumbar vertebrae in the L-1 through L-4 region.

• Have a history of Bell's palsy, other cranial nerve disorders, or have a history of Temporomandibular Joint and Muscle Disorders (TMJDs).

• Have any history of cancer within the previous 5 years, except for excised superficial lesions such as basal cell carcinoma and squamous cell carcinoma of the skin.

• Have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of constituting a risk when taking the study medication or of interfering with the interpretation of data.

• Have acute or chronic liver disease ([bilirubin >34 micromoles per liter (µmol/L) or

2.0 milligrams per deciliter (mg/dL), alanine transaminase [ALT/SGPT] >100 units per liter (U/L), or alkaline phosphatase >300 U/L)].

• Have impaired kidney function serum creatinine >135 µmol/L or >2.0 mg/dL.

• Have known allergy to LY2541546, any of diluents or excipients of LY2541546, or significant allergy to any other monoclonal antibody.

• History of excessive consumption of alcohol or abuse of drugs within the last year.

• Have poor medical condition or psychiatric risks for treatment with an investigational drug.

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.	Gainesville	Georgia	United States	30501
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.	Bethesda	Maryland	United States	20817
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.	Hvidovre		Denmark	2650
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.	Vejle		Denmark	7100
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.	Tallinn		Estonia	10128
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.	Nagano		Japan	386-0493
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.	Tokyo		Japan	166-0003
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.	Vilnius		Lithuania	10323

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01144377
• Other Study ID Numbers: 11953; I2M-MC-GSDB
• First Posted: Jun 15, 2010
• Last Update Posted: Sep 17, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: osteoporosis
• Additional relevant MeSH terms: Osteoporosis; Bone Diseases, Metabolic

Study Results

Participant Flow

Pre-assignment Detail	After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period for an additional 40 weeks (for a total of 52 weeks follow-up for the main study participants only).

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks. After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period for an additional 40 weeks (for a total of 52 weeks follow-up for the main study participants only).	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks. After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period for an additional 40 weeks (for a total of 52 weeks follow-up for the main study participants only).	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks. After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period for an additional 40 weeks (for a total of 52 weeks follow-up for the main study participants only).	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks. After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period for an additional 40 weeks (for a total of 52 weeks follow-up for the main study participants only).	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks. After exposure to study medication for the 52 week treatment phase, participants entered a 12 week non-treatment safety follow-up period with the option of staying in the non-treatment safety follow-up period (for an additional 40 weeks for a total of 52 weeks follow-up for the main study participants only).
Period Title: 52 Week Treatment Period
STARTED	31	30	30	26	37
Received at Least One Dose of Study Drug	31	30	30	25	37
COMPLETED	26	29	25	22	34
NOT COMPLETED	5	1	5	4	3
Period Title: 52 Week Treatment Period
STARTED	26	29	25	22	34
COMPLETED	26	29	25	22	34
NOT COMPLETED	0	0	0	0	0
Period Title: 52 Week Treatment Period
STARTED	22	25	23	3	23
COMPLETED	21	24	23	3	21
NOT COMPLETED	1	1	0	0	2

Baseline Characteristics

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W	Total
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	Total of all reporting groups
Overall Participants	31	30	30	25	37	153
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.78 (8.98)	64.17 (8.20)	66.12 (7.68)	63.56 (8.02)	65.17 (8.91)	65.22 (8.38)
Sex: Female, Male (Count of Participants)
Female	31 100%	30 100%	30 100%	25 100%	37 100%	153 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 12.9%	4 13.3%	2 6.7%	9 36%	8 21.6%	27 17.6%
Not Hispanic or Latino	23 74.2%	24 80%	26 86.7%	16 64%	26 70.3%	115 75.2%
Unknown or Not Reported	4 12.9%	2 6.7%	2 6.7%	0 0%	3 8.1%	11 7.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	14 45.2%	13 43.3%	13 43.3%	11 44%	14 37.8%	65 42.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	1 2.7%	1 0.7%
White	17 54.8%	17 56.7%	17 56.7%	14 56%	22 59.5%	87 56.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	4 12.9%	6 20%	5 16.7%	11 44%	10 27%	36 23.5%
Estonia	4 12.9%	3 10%	5 16.7%	3 12%	4 10.8%	19 12.4%
Lithuania	3 9.7%	4 13.3%	4 13.3%	0 0%	4 10.8%	15 9.8%
Denmark	6 19.4%	4 13.3%	3 10%	0 0%	5 13.5%	18 11.8%
Japan	14 45.2%	13 43.3%	13 43.3%	11 44%	14 37.8%	65 42.5%
Lumbar Spine Bone Mineral Density (Baseline) (grams/square centimeter (g/cm^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams/square centimeter (g/cm^2)]	0.78 (0.09)	0.78 (0.07)	0.80 (0.09)	0.77 (0.09)	0.78 (0.09)	0.78 (0.09)
Femoral Neck Bone Mineral Density (Baseline) (g/cm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/cm^2]	0.66 (0.15)	0.66 (0.15)	0.69 (0.11)	0.63 (0.11)	0.66 (0.17)	0.66 (0.14)
Total Hip Bone Mineral Density (Baseline) (grams/square centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams/square centimeter]	0.75 (0.11)	0.75 (0.13)	0.77 (0.10)	0.73 (0.11)	0.73 (0.14)	0.75 (0.12)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD)
Description	Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate.
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline lumbar spine BMD value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	27	29	26	22	34
Least Squares Mean (95% Confidence Interval) [g/cm^2]	0.065	0.115	0.142	0.054	-0.011

2. Secondary Outcome

Title	Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD)
Description	Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate
Time Frame	Baseline, 12 weeks and 24 weeks and 64 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline lumbar spine BMD value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	29	30	30	24	36
Week 12	0.028	0.048	0.057	0.039	-0.007
Week 24	0.049	0.083	0.098	0.048	-0.006
Week 64	0.046	0.098	0.135	0.046	-0.007

3. Secondary Outcome

Title	Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD)
Description	Femoral neck and total hip bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline BMD as a covariate.
Time Frame	Baseline, 24 weeks and 52 weeks and 64 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline femoral neck or total hip BMD value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	27	29	28	23	36
Femoral Neck BMD Week 24	0.010	0.017	0.026	0.002	0.002
Total Hip BMD Week 24	0.007	0.020	0.031	0.015	-0.007
Femoral Neck BMD Week 52	0.018	0.025	0.044	0.014	0.003
Total Hip BMD Week 52	0.017	0.032	0.051	0.019	-0.004
Femoral Neck BMD Week 64	0.016	0.028	0.038	0.013	0.002
Total Hip BMD Week 64	0.011	0.031	0.047	0.021	-0.007

4. Secondary Outcome

Title	Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD)
Description	Total radius of the wrist bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a 1-factor analysis of covariance model with treatment group as the main effect and baseline BMD as a covariate.
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline total radius of the wrist BMD value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	24	29	26	22	32
Least Squares Mean (95% Confidence Interval) [g/cm^2]	-0.005	-0.005	-0.001	-0.002	-0.005

5. Secondary Outcome

Title	Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP)
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline bone-specific alkaline phosphatase value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	27	29	26	22	33
Median (Inter-Quartile Range) [units/liter]	-6.000	-2.000	1.600	-3.150	-3.900

6. Secondary Outcome

Title	Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx)
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline serum type I collagen fragment value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	26	29	25	21	32
Median (Inter-Quartile Range) [nanograms/milliliter]	-0.014	-0.088	-0.038	-0.022	0.037

7. Secondary Outcome

Title	Change From Baseline to 52 Week Endpoint in Osteocalcin
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline osteocalcin value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	26	29	25	22	32
Median (Inter-Quartile Range) [micrograms/liter]	-2.087	-0.764	0.823	-3.322	-2.029

8. Secondary Outcome

Title	Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP)
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with baseline and at least one post-baseline serum N-terminal extension propeptide of type I collagen value.

Arm/Group Title	180 mg LY2541546 Q4W + Placebo	180 mg LY2541546 Q2W	270 mg LY2541546 Q2W	270 mg LY2541546 Q12W + Placebo	Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.	LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.	LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.	Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
Measure Participants	26	29	25	22	32
Median (Inter-Quartile Range) [nanograms/milliliter]	-12.250	-4.200	-1.100	-16.050	-5.800

Adverse Events

Arm/Group Title	180 mg LY2541546 Q4W + Placebo		180 mg LY2541546 Q2W		270 mg LY2541546 Q2W		270 mg LY2541546 Q12W + Placebo		Placebo Q2W
Arm/Group Description	LY2541546 + Placebo: 180 milligrams (mg) LY2541546 administered subcutaneously every 4 weeks (Q4W) for 52 weeks with Placebo administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.		LY2541546: 180 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.		LY2541546: 270 mg administered subcutaneously every 2 weeks (Q2W) for 52 weeks.		LY2541546 + Placebo: 270 mg LY2541546 administered subcutaneously every 12 weeks (Q12W) with Placebo administered subcutaneously every 2 weeks when LY2541546 is not administered for 52 weeks.		Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
All Cause Mortality
	180 mg LY2541546 Q4W + Placebo		180 mg LY2541546 Q2W		270 mg LY2541546 Q2W		270 mg LY2541546 Q12W + Placebo		Placebo Q2W
	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)
Serious Adverse Events
	180 mg LY2541546 Q4W + Placebo		180 mg LY2541546 Q2W		270 mg LY2541546 Q2W		270 mg LY2541546 Q12W + Placebo		Placebo Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/31 (12.9%)		3/30 (10%)		4/30 (13.3%)		1/25 (4%)		2/37 (5.4%)
Cardiac disorders
Cardiac failure	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Eye disorders
Retinal artery occlusion	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1	0/25 (0%)	0	0/37 (0%)	0
Gastrointestinal disorders
Mechanical ileus	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Infections and infestations
Pneumonia	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Pyelonephritis	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Ligament rupture	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/31 (3.2%)	1	1/30 (3.3%)	1	2/30 (6.7%)	2	0/25 (0%)	0	0/37 (0%)	0
Metastases to bone	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Metastases to lymph nodes	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Pancreatic carcinoma	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Nervous system disorders
Cerebral infarction	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Spinal cord ischaemia	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	2	0/25 (0%)	0	0/37 (0%)	0
Reproductive system and breast disorders
Uterine prolapse	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	1/25 (4%)	1	0/37 (0%)	0
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/31 (0%)	0	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Other (Not Including Serious) Adverse Events
	180 mg LY2541546 Q4W + Placebo		180 mg LY2541546 Q2W		270 mg LY2541546 Q2W		270 mg LY2541546 Q12W + Placebo		Placebo Q2W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/31 (96.8%)		28/30 (93.3%)		29/30 (96.7%)		21/25 (84%)		34/37 (91.9%)
Blood and lymphatic system disorders
Anaemia	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Cardiac disorders
Ventricular extrasystoles	3/31 (9.7%)	5	0/30 (0%)	0	1/30 (3.3%)	1	1/25 (4%)	1	0/37 (0%)	0
Ear and labyrinth disorders
Vertigo	2/31 (6.5%)	6	0/30 (0%)	0	0/30 (0%)	0	2/25 (8%)	2	0/37 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/31 (0%)	0	1/30 (3.3%)	1	2/30 (6.7%)	2	1/25 (4%)	1	0/37 (0%)	0
Abdominal pain upper	1/31 (3.2%)	1	1/30 (3.3%)	1	3/30 (10%)	3	0/25 (0%)	0	2/37 (5.4%)	2
Constipation	1/31 (3.2%)	1	1/30 (3.3%)	1	2/30 (6.7%)	2	1/25 (4%)	1	1/37 (2.7%)	1
Dental caries	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Diarrhoea	0/31 (0%)	0	5/30 (16.7%)	5	3/30 (10%)	3	1/25 (4%)	1	2/37 (5.4%)	4
Gastritis	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Nausea	2/31 (6.5%)	2	0/30 (0%)	0	1/30 (3.3%)	1	0/25 (0%)	0	2/37 (5.4%)	4
Periodontal disease	1/31 (3.2%)	1	0/30 (0%)	0	1/30 (3.3%)	1	0/25 (0%)	0	2/37 (5.4%)	2
General disorders
Fatigue	2/31 (6.5%)	3	1/30 (3.3%)	1	1/30 (3.3%)	1	0/25 (0%)	0	4/37 (10.8%)	4
Injection site bruising	1/31 (3.2%)	4	3/30 (10%)	9	2/30 (6.7%)	7	6/25 (24%)	11	3/37 (8.1%)	3
Injection site erythema	3/31 (9.7%)	3	3/30 (10%)	5	2/30 (6.7%)	3	0/25 (0%)	0	0/37 (0%)	0
Injection site haemorrhage	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	3
Injection site induration	2/31 (6.5%)	2	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Injection site pain	4/31 (12.9%)	7	5/30 (16.7%)	8	1/30 (3.3%)	2	1/25 (4%)	1	1/37 (2.7%)	1
Injection site pruritus	2/31 (6.5%)	2	5/30 (16.7%)	7	4/30 (13.3%)	5	0/25 (0%)	0	0/37 (0%)	0
Injection site reaction	0/31 (0%)	0	2/30 (6.7%)	6	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Injection site swelling	6/31 (19.4%)	11	3/30 (10%)	5	5/30 (16.7%)	15	2/25 (8%)	3	0/37 (0%)	0
Oedema peripheral	2/31 (6.5%)	2	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Hepatobiliary disorders
Hepatic cyst	1/31 (3.2%)	1	0/30 (0%)	0	1/30 (3.3%)	1	0/25 (0%)	0	2/37 (5.4%)	2
Infections and infestations
Asymptomatic bacteriuria	1/31 (3.2%)	1	0/30 (0%)	0	3/30 (10%)	3	0/25 (0%)	0	0/37 (0%)	0
Bronchitis	3/31 (9.7%)	4	1/30 (3.3%)	1	2/30 (6.7%)	2	1/25 (4%)	2	2/37 (5.4%)	2
Cystitis	4/31 (12.9%)	4	1/30 (3.3%)	1	1/30 (3.3%)	1	2/25 (8%)	2	2/37 (5.4%)	3
Gastroenteritis	0/31 (0%)	0	2/30 (6.7%)	2	1/30 (3.3%)	1	1/25 (4%)	1	1/37 (2.7%)	1
Gastrointestinal viral infection	0/31 (0%)	0	1/30 (3.3%)	1	2/30 (6.7%)	2	0/25 (0%)	0	0/37 (0%)	0
Herpes simplex	0/31 (0%)	0	1/30 (3.3%)	1	2/30 (6.7%)	2	1/25 (4%)	1	0/37 (0%)	0
Herpes zoster	1/31 (3.2%)	1	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Influenza	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	1/25 (4%)	1	2/37 (5.4%)	2
Nasopharyngitis	16/31 (51.6%)	20	8/30 (26.7%)	11	11/30 (36.7%)	19	7/25 (28%)	8	12/37 (32.4%)	16
Oral herpes	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Periodontitis	0/31 (0%)	0	0/30 (0%)	0	2/30 (6.7%)	2	0/25 (0%)	0	3/37 (8.1%)	3
Pharyngitis	1/31 (3.2%)	1	3/30 (10%)	4	3/30 (10%)	3	1/25 (4%)	1	1/37 (2.7%)	1
Pneumonia	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Pulpitis dental	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	3/37 (8.1%)	3
Respiratory tract infection viral	3/31 (9.7%)	3	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Rhinitis	0/31 (0%)	0	0/30 (0%)	0	4/30 (13.3%)	4	0/25 (0%)	0	2/37 (5.4%)	2
Sinusitis	1/31 (3.2%)	1	2/30 (6.7%)	2	1/30 (3.3%)	1	1/25 (4%)	1	1/37 (2.7%)	1
Upper respiratory tract infection	0/31 (0%)	0	1/30 (3.3%)	1	4/30 (13.3%)	4	2/25 (8%)	2	1/37 (2.7%)	1
Urinary tract infection	1/31 (3.2%)	1	2/30 (6.7%)	2	0/30 (0%)	0	2/25 (8%)	2	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Contusion	3/31 (9.7%)	3	1/30 (3.3%)	3	2/30 (6.7%)	2	0/25 (0%)	0	5/37 (13.5%)	6
Fall	0/31 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Joint dislocation	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Ligament sprain	0/31 (0%)	0	2/30 (6.7%)	2	1/30 (3.3%)	1	0/25 (0%)	0	2/37 (5.4%)	2
Investigations
Blood 1,25-dihydroxycholecalciferol increased	6/31 (19.4%)	6	4/30 (13.3%)	5	4/30 (13.3%)	4	2/25 (8%)	2	5/37 (13.5%)	5
Hepatic enzyme increased	1/31 (3.2%)	1	0/30 (0%)	0	2/30 (6.7%)	2	0/25 (0%)	0	0/37 (0%)	0
Urine calcium decreased	2/31 (6.5%)	2	2/30 (6.7%)	2	1/30 (3.3%)	1	0/25 (0%)	0	0/37 (0%)	0
Urine phosphorus decreased	2/31 (6.5%)	2	1/30 (3.3%)	1	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Metabolism and nutrition disorders
Hypercholesterolaemia	1/31 (3.2%)	1	3/30 (10%)	3	1/30 (3.3%)	1	1/25 (4%)	1	2/37 (5.4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/31 (6.5%)	3	3/30 (10%)	5	2/30 (6.7%)	2	2/25 (8%)	2	5/37 (13.5%)	5
Back pain	6/31 (19.4%)	6	3/30 (10%)	4	2/30 (6.7%)	2	2/25 (8%)	2	4/37 (10.8%)	4
Bone pain	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	2/37 (5.4%)	2
Bursitis	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Joint swelling	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Muscle spasms	0/31 (0%)	0	2/30 (6.7%)	3	1/30 (3.3%)	1	0/25 (0%)	0	0/37 (0%)	0
Musculoskeletal pain	2/31 (6.5%)	2	3/30 (10%)	3	1/30 (3.3%)	1	1/25 (4%)	1	0/37 (0%)	0
Musculoskeletal stiffness	2/31 (6.5%)	2	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Myalgia	2/31 (6.5%)	4	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Osteoarthritis	1/31 (3.2%)	1	4/30 (13.3%)	4	1/30 (3.3%)	1	1/25 (4%)	1	2/37 (5.4%)	3
Pain in extremity	2/31 (6.5%)	2	0/30 (0%)	0	2/30 (6.7%)	2	1/25 (4%)	1	1/37 (2.7%)	1
Tendonitis	1/31 (3.2%)	1	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	2/31 (6.5%)	2	0/30 (0%)	0	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Nervous system disorders
Cervicobrachial syndrome	0/31 (0%)	0	0/30 (0%)	0	1/30 (3.3%)	1	0/25 (0%)	0	3/37 (8.1%)	3
Dizziness	1/31 (3.2%)	1	0/30 (0%)	0	1/30 (3.3%)	1	1/25 (4%)	1	2/37 (5.4%)	2
Headache	2/31 (6.5%)	2	3/30 (10%)	4	0/30 (0%)	0	0/25 (0%)	0	1/37 (2.7%)	1
Sciatica	0/31 (0%)	0	1/30 (3.3%)	1	3/30 (10%)	6	0/25 (0%)	0	0/37 (0%)	0
Psychiatric disorders
Insomnia	0/31 (0%)	0	2/30 (6.7%)	2	0/30 (0%)	0	0/25 (0%)	0	0/37 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/31 (0%)	0	1/30 (3.3%)	1	1/30 (3.3%)	1	1/25 (4%)	1	5/37 (13.5%)	5
Skin and subcutaneous tissue disorders
Dermatitis	2/31 (6.5%)	2	4/30 (13.3%)	6	1/30 (3.3%)	1	0/25 (0%)	0	0/37 (0%)	0
Dermatitis allergic	0/31 (0%)	0	1/30 (3.3%)	1	2/30 (6.7%)	2	0/25 (0%)	0	0/37 (0%)	0
Eczema	3/31 (9.7%)	4	2/30 (6.7%)	3	1/30 (3.3%)	1	2/25 (8%)	3	2/37 (5.4%)	2
Pruritus	0/31 (0%)	0	2/30 (6.7%)	3	1/30 (3.3%)	2	0/25 (0%)	0	0/37 (0%)	0
Rash	0/31 (0%)	0	2/30 (6.7%)	3	2/30 (6.7%)	2	2/25 (8%)	2	0/37 (0%)	0
Vascular disorders
Hypertension	1/31 (3.2%)	1	1/30 (3.3%)	1	3/30 (10%)	4	0/25 (0%)	0	3/37 (8.1%)	3

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.