A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)

Osteopenia Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women With Low Bone Mass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01825785
• Other study ID #: 20060221
• Status: Completed
• Phase: Phase 1
• Start date: November 14, 2007
• Est. completion date: December 2, 2008

Study information

• Verified date: April 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to assess the safety, tolerability, and immunogenicity potential of romosozumab following multiple subcutaneous (SC) administrations in healthy men and postmenopausal women with low bone mass.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2, 2008
• Est. primary completion date: December 2, 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

Inclusion Criteria:

• Healthy males and females between 45 to 80 years of age

• Postmenopausal females

• Low bone mineral density, defined by bone mineral density (BMD) T-scores between -1.0 and -2.5, inclusive, for the lumbar spine [L1-L4] or total evaluable vertebrae [if fewer than L1-L4] or total hip)

• 25-hydroxyvitamin D = 20 ng/mL

• Weight = 98 kg (216 lb) and/or height = 196 cm (77 in)

Exclusion Criteria:

• Osteoporosis defined by bone mineral density (BMD) T-scores < -2.5 for the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4) or total hip

• Diagnosed with any condition that would affect bone metabolism

• Previous exposure to AMG 785

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Osteopenia
• Postmenopausal

Intervention

Drug:
• Romosozumab
Administered by subcutaneous injection
• Placebo
Administered by subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	Serious adverse events were any events that were fatal, were life-threatening (placed the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, were congenital anomalies or birth defects, or were other significant medical hazards.; Relatedness to investigational product was assessed by the investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?'	169 days
Primary	Number of Participants Who Developed Antibodies to Romosozumab	All samples were tested for binding anti-romsozumab antibodies using an immunoassay; all antibody-positive samples were further tested in a bioassay to determine if the antibodies were neutralizing.; Development of antibodies to romosozumab is defined as participants with a negative result at baseline and a positive result at any time postbaseline.	Blood samples for detection of anti-romosozumab antibodies were collected at day 1 (predose) and days 29 (predose), 57 (predose), 85, 113, 141, and 169.
Secondary	Time to Maximum Observed Concentration (Tmax) of Romosozumab	Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
Secondary	Maximum Observed Concentration (Cmax) of Romosozumab		Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
Secondary	Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab	Area under the serum romosozumab concentration-time curve from time 0 to tau (tau = 14 days for Q2W dose cohorts and 28 days for Q4W dose cohorts)	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
Secondary	Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab		Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.
Secondary	Accumulation Ratio (AR) for Romosozumab	The accumulation ratio (AR) was calculated as the ratio of AUC0-tau after the last dose to AUC0-tau after the first dose.	Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.
Secondary	Percent Change From Baseline in Bone Mineral Density of the Total Spine	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and assessed by a central lab.	Baseline and days 29, 85, 127, and 169
Secondary	Percent Change From Baseline in Bone Mineral Density at the Total Hip	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.	Baseline and days 29, 85, 127, and 169
Secondary	Percent Change From Baseline in Bone Mineral Density at the Femoral Hip	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.	Baseline and days 29, 85, 127, and 169
Secondary	Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.	Baseline and days 29, 85, 127, and 169
Secondary	Percent Change From Baseline in Bone Mineral Density at the Total Wrist	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.	Baseline and days 29, 85, 127, and 169
Secondary	Percent Change From Baseline in Bone Mineral Density of the Whole Body	Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.	Baseline and days 29, 85, 127, and 169
Secondary	Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP)		Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
Secondary	Percent Change From Baseline in Osteocalcin		Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
Secondary	Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)		Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
Secondary	Percent Change From Baseline in Serum C-telopeptide (sCTX)		Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
Secondary	Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)		Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169
Secondary	Percent Change From Baseline in Sclerostin		Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169
Secondary	Change From Baseline in Ionized Calcium		Baseline and day 169 (or earlier for participants who discontinued before day 169)

External Links

•   AmgenTrials clinical trials website