Clinical trial NCT01825785: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Postmenopausal
Osteopenia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-04-08
Enrollment: 48
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 169 days
measure: Number of Participants Who Developed Antibodies to Romosozumab
timeFrame: 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 outcomes:
measure: Time to Maximum Observed Concentration (Tmax) of Romosozumab
timeFrame: 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.
measure: Maximum Observed Concentration (Cmax) of Romosozumab
timeFrame: 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.
measure: Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab
timeFrame: 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.
measure: Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab
timeFrame: Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.
measure: Accumulation Ratio (AR) for Romosozumab
timeFrame: 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.
measure: Percent Change From Baseline in Bone Mineral Density of the Total Spine
timeFrame: Baseline and days 29, 85, 127, and 169
measure: Percent Change From Baseline in Bone Mineral Density at the Total Hip
timeFrame: Baseline and days 29, 85, 127, and 169
measure: Percent Change From Baseline in Bone Mineral Density at the Femoral Hip
timeFrame: Baseline and days 29, 85, 127, and 169
measure: Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius
timeFrame: Baseline and days 29, 85, 127, and 169
measure: Percent Change From Baseline in Bone Mineral Density at the Total Wrist
timeFrame: Baseline and days 29, 85, 127, and 169
measure: Percent Change From Baseline in Bone Mineral Density of the Whole Body
timeFrame: Baseline and days 29, 85, 127, and 169
measure: Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP)
timeFrame: 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
measure: Percent Change From Baseline in Osteocalcin
timeFrame: 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
measure: Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
timeFrame: 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
measure: Percent Change From Baseline in Serum C-telopeptide (sCTX)
timeFrame: 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
measure: Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)
timeFrame: 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
measure: Percent Change From Baseline in Sclerostin
timeFrame: Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169
measure: Change From Baseline in Ionized Calcium
timeFrame: Baseline and day 169 (or earlier for participants who discontinued before day 169)
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: