Clinical trial NCT01833754: Study of Romosozumab (AMG 785) Administered to Healthy Participants and Patients With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis
Official title: A Phase 1, Open-label, Single-dose Study of Romosozumab (AMG 785) Administered Subcutaneously to Healthy Subjects and Subjects With Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoporosis
Keywords: Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-04-17
Enrollment: 24
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis.


Eligibility criteria: INCLUSION CRITERIA - ALL SUBJECTS :

* Males or females ≥ 50 years of age
* Body weight ≥ 45 and ≤ 110 kg
* Willing to adhere to calcium and vitamin D supplementation requirements
* Females must be of non-reproductive potential

INCLUSION CRITERIA - SUBJECTS WITH RENAL IMPAIRMENT (GROUPS 1 AND 2):

* Group 1 - Stage 4 RI (estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m²)
* Group 2 - End stage renal disease requiring hemodialysis

INCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3):

• Renal function defined as an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73 m²

EXCLUSION CRITERIA - ALL SUBJECTS:

* History of metabolic or bone disease (except for metabolic bone disease in renal impairment (RI) subjects)
* History of osteoporosis, vertebral fracture, or fragility fracture of the wrist, humerus, hip, or pelvis after age 50
* Recent bone fracture
* Vitamin D insufficiency
* Hypocalcemia or hypercalcemia
* Hypomagnesemia
* Hypophosphatemia
* Untreated hyper- or hypothyroidism
* Females with a positive pregnancy test
* Males with pregnant partners
* Females who are lactating/breastfeeding or plan to breastfeed on study and for 3 months after receiving the dose of study drug
* History of spinal stenosis
* History of facial nerve paralysis
* Positive for human immunodeficiency virus (HIV) antibodies
* Positive for hepatitis B surface antigen or detectable hepatitis C
* Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical, or breast ductal carcinoma in situ) within 5 years before screening
* History of solid organ or bone marrow transplants EXCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3)
* Current hyper- or hypoparathyroidism

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of study drug up to day 85
measure: Number of Participants Who Developed Anti-Romosozumab Antibodies
timeFrame: Baseline and day 85
measure: Albumin-Adjusted Serum Calcium Concentrations by Visit
timeFrame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
measure: Intact Parathyroid Hormone (iPTH)Concentrations by Visit
timeFrame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Romosozumab
timeFrame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
measure: Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab
timeFrame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
measure: Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
timeFrame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
timeFrame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Orangeburg
country: United States
facility: Research Site
state: South Carolina
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.