Safety And Tolerability Study Of RN564 In Women With Osteopenia And Healthy Men.

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety and tolerability of RN564 in women with osteopenia and healthy men.

Official Title
-----------------
A Phase I Study To Evaluate The Safety, Tolerability, Immunogenicity, Pharmacokinetics And Pharmacodynamics Of Escalating Doses Of RN564 In Women With Osteopenia And In Healthy Men

Conditions
-----------------
Osteopenia, Osteoporosis, Bone Disease

Intervention / Treatment
-----------------
* Biological: RN564


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of osteopenia for women (BMD T-scores between -1.0 and - 2.5 SD at the lumbar spine, the femoral neck or total hip) Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >45 kg (99 lbs). Have at least 3 vertebral bodies in the L1-L4 region and one femoral neck site that are accessible by DXA. Exclusion Criteria: Evidence or history of any underlying condition, other than primary osteopenia, that affect bone metabolism (eg, hyperparathyroidism, hypoparathyroidism). Subjects with pre-existing periodontal/dental disease or those who have undergone invasive dental procedures (eg, tooth extraction, oral surgery) within 60 days prior to Day -1. If QTcF exceeds 455 msec, the ECG should be repeated two more times and the average of the three QTcF values should be used to determine the subject's eligibility.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Biological: RN564<br>* Intravenous, single dose with experimental dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting or intolerable treatment related adverse events (AEs) |  | Duration of the study | 
| Incidence, severity and causal relationship of treatment emergent AEs (TEAEs) |  | Duration of the study | 
| Incidence of abnormal laboratory findings (clinical chemistry, hematology and urinalysis) |  | Duration of the study | 
| Changes from baseline in safety laboratory assessments. |  | Duration of the study | 
| Abnormal and clinically relevant changes in vital signs, BP, and ECG parameters. |  | Duration of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The PK parameter estimates will include but not be limited to: AUC(0-t[last]), Tmax, Cmax, terminal elimination half-life (t1/2), Clearance (CL), apparent volume of distribution (Vz), volume of distribution at steady state (Vss), and AUC of RN564. |  | Days 1, 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 | 
| Percentage change from baseline (average of Day -1 and Day 1 prior to infusion of RN564) in total DKK-1 concentrations over time inclusive of 85 days. |  | Days -1, 1, 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 | 
| Percentage change from baseline (average of Day -1 and Day 1 prior to infusion of RN564) in serum PINP, NTX, CTX, bone specific alkaline phosphatase and osteocalcin over time inclusive of 85 days. |  | Days -1, 1, 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 | 
| Percentage change from baseline in lumbar spine, total hip, femoral neck and distal radius BMD at Day 85. |  | Day -1 and 85 | 
| PK/PD model describing the relationship between RN564 PK parameter estimates/concentrations and changes in pharmacodynamic endpoints. |  | Duration of the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase 1, Osteopenia, RN564