Study of Romosozumab (AMG 785) Administered to Healthy Pa... | NCT01833754

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1: Stage 4 Renal Impairment	Experimental	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Drug: Romosozumab
Group 2: ESRD Requiring Hemodialysis	Experimental	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	Drug: Romosozumab
Group 3: Healthy Participants	Experimental	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	Drug: Romosozumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Romosozumab	Drug	Administered as three 70 mg/mL prefilled syringe injections	Group 1: Stage 4 Renal Impairment Group 2: ESRD Requiring Hemodialysis

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events	A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: fatal life-threatening required in-patient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"	From the first dose of study drug up to day 85
Number of Participants Who Developed Anti-Romosozumab Antibodies	Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.	Baseline and day 85
Albumin-Adjusted Serum Calcium Concentrations by Visit	Albumin-adjusted calcium was derived as: Where serum albumin < 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 * [40 - serum albumin (g/L)]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.	Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Intact Parathyroid Hormone (iPTH)Concentrations by Visit		Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

Secondary Outcomes

Measure	Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of Romosozumab		Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab		Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

Eligibility Module

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Tempe	Arizona	85284	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
35304747	Background	Hsu CP, Maddox J, Block G, Bartley Y, Yu Z. Influence of Renal Function on Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Romosozumab. J Clin Pharmacol. 2022 Sep;62(9):1132-1141. doi: 10.1002/jcph.2050. Epub 2022 Apr 2.

Label	URL
AmgenTrials clinical trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
FG001	Group 2: ESRD Requiring Hemodialysis

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
BG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
BG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0008 BG0018 BG0028 BG00324

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

Number of Participants With Adverse Events

A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria:

fatal
life-threatening
required in-patient hospitalization or prolongation of existing hospitalization
resulted in persistent or significant disability/incapacity
congenital anomaly/birth defect
other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a "yes" response to the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?"

All participants who received study drug

Posted

Count of Participants

Participants

From the first dose of study drug up to day 85

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Units	Counts
Participants	OG0008 OG0018 OG0028

Title

Denominators

Categories

All adverse events

Title	Measurements
	OG0007 OG0016 OG0020

Serious adverse events

Secondary

Maximum Observed Serum Concentration (Cmax) of Romosozumab

All participants were included in the analysis

Posted

Mean

Standard Deviation

µg/mL

Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Units	Counts
Participants

Secondary

Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab

All participants were included in the analysis

Posted

Median

Full Range

days

Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Units	Counts
Participants

Secondary

Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)

All participants were included in the analysis

Posted

Mean

Standard Deviation

days*µg/mL

Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Units	Counts
Participants

Secondary

Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)

All participants were included in the analysis

Posted

Mean

Standard Deviation

days*µg/mL

Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Units	Counts
Participants

Primary

Number of Participants Who Developed Anti-Romosozumab Antibodies

Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab.

If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

All participants who received study drug

Posted

Count of Participants

Participants

Baseline and day 85

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants

Primary

Albumin-Adjusted Serum Calcium Concentrations by Visit

Albumin-adjusted calcium was derived as:

Where serum albumin < 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 * [40 - serum albumin (g/L)]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.

All participants who received study drug

Posted

Mean

Standard Deviation

mmol/L

Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Primary

Intact Parathyroid Hormone (iPTH)Concentrations by Visit

All participants who received study drug and with available data at each time point

Posted

Mean

Standard Deviation

pmol/L

Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit

ID	Title	Description
OG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.
OG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1: Stage 4 Renal Impairment	Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	1	8	7	8
EG001	Group 2: ESRD Requiring Hemodialysis	Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1.	1	8	6	8
EG002	Group 3: Healthy Participants	Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1.	0	8	0	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Hyperparathyroidism	Endocrine disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Hyperparathyroidism secondary	Endocrine disorders	MedDRA 16.1	Systematic Assessment	EG0004 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Constipation	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0012 affected8 at risk EG0020 affected8 at risk
Gastritis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Gingival recession	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Nausea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Injection site pruritus	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Wound	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Blood creatinine increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Glomerular filtration rate decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Heart rate increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Gout	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0014 affected8 at risk EG0020 affected8 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Headache	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Sciatica	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk

ID	Term
D001851	Bone Diseases, Metabolic
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment		EG0001 affected8 at risk EG0010 affected8 at risk EG0020 affected8 at risk
Mitral valve disease	Cardiac disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected8 at risk EG0011 affected8 at risk EG0020 affected8 at risk