A Single-dose Study Evaluating Romosozumab (AMG 785) in Healthy Postmenopausal Japanese and Non-Japanese Women

Osteopenia Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Postmenopausal Japanese Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01101061
• Other study ID #: 20090378
• Status: Completed
• Phase: Phase 1
• Start date: May 3, 2010
• Est. completion date: November 1, 2010

Study information

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

Clinical Trial Summary

The main purpose of this study is to assess the safety, tolerability and potential immune response to romosozumab following single subcutaneous (SC; injection under the skin) dose administration in healthy postmenopausal Japanese and non-Japanese women.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: November 1, 2010
• Est. primary completion date: November 1, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

Inclusion Criteria:

• Japanese subjects must be first (4 grandparents, biologic parents and subject born in Japan), second (4 grandparents and biological parents born in Japan) or third (4 grandparents born in Japan) generation Japanese

• Body mass index = 25 kg/m², inclusive at screening

• Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy) as documented in medical history (verified with an operative note, if available)

Exclusion Criteria:

• Osteoporosis, as defined by bone mineral density (BMD) T-scores of the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4); or femoral neck = -2.5

• History of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis;

• Diagnosed with any condition that will affect bone metabolism

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Osteopenia

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	A serious adverse event (SAE) is defined as an adverse event that; is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product.	Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments.
Primary	Number of Participants Who Developed Anti-romosozumab Binding Antibodies	Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline.	Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo)
Primary	Serum Calcium Levels		Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Primary	Serum Intact Parathyroid Hormone (iPTH) Levels		Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Secondary	Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)		Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Secondary	Maximum Percent Change From Baseline in Serum C-telopeptide (CTX)		Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Secondary	Percent Change From Baseline in Sclerostin		Baseline and days 12, 29, 43, 57, 71, and 85
Secondary	Time to Maximum Observed Concentration of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Secondary	Maximum Observed Concentration of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Secondary	Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Secondary	Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Secondary	Apparent Clearance (CL/F) of Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Secondary	Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,ß) for Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Secondary	Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,?) for Romosozumab	Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.	Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.

External Links

•   AmgenTrials clinical trials website