Clinical trial NCT01101061: A Single-dose Study Evaluating Romosozumab (AMG 785) in Healthy Postmenopausal Japanese and Non-Japanese Women
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteopenia
Keywords: Amgen
Phase 1
Postmenopausal
Japanese
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-04-09
Enrollment: 31
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 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.
measure: Number of Participants Who Developed Anti-romosozumab Binding Antibodies
timeFrame: 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)
measure: Serum Calcium Levels
timeFrame: Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
measure: Serum Intact Parathyroid Hormone (iPTH) Levels
timeFrame: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Secondary outcomes:
measure: Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
timeFrame: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
measure: Maximum Percent Change From Baseline in Serum C-telopeptide (CTX)
timeFrame: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
measure: Percent Change From Baseline in Sclerostin
timeFrame: Baseline and days 12, 29, 43, 57, 71, and 85
measure: Time to Maximum Observed Concentration of Romosozumab
timeFrame: 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.
measure: Maximum Observed Concentration of Romosozumab
timeFrame: 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.
measure: Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab
timeFrame: 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.
measure: Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab
timeFrame: 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.
measure: Apparent Clearance (CL/F) of Romosozumab
timeFrame: 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.
measure: Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab
timeFrame: 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.
measure: Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: