Efficacy, Safety and Tolerability of Romosozumab in the T... | NCT01992159

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Placebo
Romosozumab 70 mg	Experimental	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romosozumab
Romosozumab 140 mg	Experimental	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romosozumab
Romosozumab 210 mg	Experimental	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.	Drug: Romosozumab

Name	Type	Description	Arm Group Labels	Other Names
Romosozumab	Drug	Administered by subcutaneous injection	Romosozumab 140 mg Romosozumab 210 mg Romosozumab 70 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.	Baseline and 12 months

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine	Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.	Baseline and 6 months
Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip

Eligibility Module

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Anjyo-shi	Aichi-ken	446-0063	Japan
Research Site

PubMed Identifier	Type	Citation	Retractions
28687496	Background	Ishibashi H, Crittenden DB, Miyauchi A, Libanati C, Maddox J, Fan M, Chen L, Grauer A. Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study. Bone. 2017 Oct;103:209-215. doi: 10.1016/j.bone.2017.07.005. Epub 2017 Jul 5.

Label	URL
AmgenTrials clinical trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
FG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
BG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
BG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
BG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG00263 ParticipantsBG003

Age, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Lumbar Spine Bone Mineral Density (BMD) T-score

The T-score is the bone mineral density (BMD) at the site when compared to that of a healthy thirty-year-old. Normal is a T-score of -1.0 or higher; Osteopenia is defined as between -1.0 and -2.5; Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty-year-old man/woman.

Mean

Standard Deviation

T-score

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Total Hip BMD T-score

Mean

Standard Deviation

T-score

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Femoral Neck BMD T-score

Mean

Standard Deviation

T-score

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Serum Procollagen Type 1 N-telopeptide (P1NP)

Participants with available data

Median

Inter-Quartile Range

μg/L

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00162 ParticipantsBG002

Serum Type 1 Collagen C-telopeptide (CTX)

Median

Inter-Quartile Range

ng/L

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Osteocalcin

Median

Inter-Quartile Range

μg/L

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00163 ParticipantsBG002

Bone Specific Alkaline Phosphatase (BSAP)

Participants with available data

Mean

Inter-Quartile Range

μg/L

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00162 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline to 12 Months in Bone Mineral Density at the Lumbar Spine

Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, and had at least 1 postbaseline measurement (primary efficacy subset).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline and 12 months

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Units	Counts
Participants	OG00059 OG00155 OG00262 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.9(0.1 to 1.8) OG0018.4(7.6 to 9.3) OG00213.3(12.1 to 14.5) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary analysis was based on a repeated measures model with the percent change from baseline at months 6 and 12 in BMD of the lumbar spine as the dependent variable, and baseline BMD, machine type, interaction of baseline BMD and machine type, visit (categorical), treatment (categorical), and interaction of treatment and visit as the independent variables; using an unstructured variance covariance structure.	Repeated Measures Model		< 0.0001	P-values were adjusted for multiplicity using a combination of a sequential test procedure and Hochberg's method to control type 1 error for the primary endpoint.	Treatment Difference	7.5			1-Sided	95	6.5

Secondary

Percent Change From Baseline at 6 Months in Bone Mineral Density at the Lumbar Spine

Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline and 6 months

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg

Secondary

Percent Change From Baseline at 6 Months in Bone Mineral Density at the Total Hip

Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline and 6 months

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg

Secondary

Percent Change From Baseline to 12 Months in Bone Mineral Density at the Total Hip

Bone density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline and 12 months

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg

Secondary

Percent Change From Baseline to 6 Months in Bone Mineral Density at the Femoral Neck

Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline and 6 months

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg

Secondary

Percent Change From Baseline to 12 Months in Bone Mineral Density at the Femoral Neck

Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging reader.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline and 12 months

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg

Secondary

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)

Randomized participants who received at least 10 doses of the assigned randomized treatment, never received any dose of incorrect treatment, had no missing baseline values, had at least 1 postbaseline measurement and with available data at each time point.

Posted

Mean

Standard Deviation

percent change

Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Secondary

Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)

Posted

Mean

Standard Deviation

percent change

Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Secondary

Percent Change From Baseline in Osteocalcin

Posted

Mean

Standard Deviation

percent change

Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Secondary

Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP)

Posted

Mean

Standard Deviation

percent change

Baseline, week 1, and months 1, 2, 3, 6, 9, and 12

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Secondary

Area Under the Curve Through Month 12 of P1NP

Randomized participants who received at least 10 doses of the assigned randomized treatment, had never received any dose of incorrect treatment, and had no missing P1NP measurements.

Posted

Least Squares Mean

95% Confidence Interval

ug*month/L

Baseline, week 1 and months 1, 2, 3, 6, 9, and 12.

ID	Title	Description
OG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.
OG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.
OG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo matching to romosozumab administered by subcutaneous injection once a month for 12 months.	5	63	20	63
EG001	Romosozumab 70 mg	Participants received 70 mg romosozumab administered by subcutaneous injection once a month for 12 months.	6	63	33	63
EG002	Romosozumab 140 mg	Participants received 140 mg romosozumab administered by subcutaneous injection once a month for 12 months.	3	63	29	63
EG003	Romosozumab 210 mg	Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months.	2	63	32	63

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG0030 affected63 at risk
Angina pectoris	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Atrioventricular block second degree	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Cataract	Eye disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Vitreous haemorrhage	Eye disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Cellulitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Heat illness	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Meniscus injury	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG003
Parkinson's disease	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Depression	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Endometrial hypertrophy	Reproductive system and breast disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0020 affected63 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0004 affected63 at risk EG0010 affected63 at risk EG0021 affected63 at risk EG0033 affected63 at risk
Dental caries	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0014 affected63 at risk EG0023 affected63 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0008 affected63 at risk EG00117 affected63 at risk EG00217 affected63 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0002 affected63 at risk EG0011 affected63 at risk EG0024 affected63 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0005 affected63 at risk EG0016 affected63 at risk EG0022 affected63 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0004 affected63 at risk EG0011 affected63 at risk EG0020 affected63 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0004 affected63 at risk EG0012 affected63 at risk EG0025 affected63 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk EG0022 affected63 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk EG0021 affected63 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0014 affected63 at risk EG0021 affected63 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected63 at risk EG0014 affected63 at risk EG0025 affected63 at risk EG003
Hypertension	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected63 at risk EG0011 affected63 at risk EG0025 affected63 at risk EG003

ID	Term
D015663	Osteoporosis, Postmenopausal
D010024	Osteoporosis
D001851	Bone Diseases, Metabolic
D001847	Bone Diseases
D009140	Musculoskeletal Diseases

ID	Term
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases