Clinical trial NCT01293487: Safety And Tolerability Study Of RN564 In Women With Osteopenia And Healthy Men.
Official title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ESCALATING DOSES OF RN564 IN WOMEN WITH OSTEOPENIA AND IN HEALTHY MEN
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteopenia
Osteoporosis
Bone Disease
Keywords: Phase 1
Osteopenia
RN564
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-02-10
Enrollment: 68
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and tolerability of RN564 in women with osteopenia and healthy men.


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.

Primary outcomes:
measure: Number of Participants With Dose-Limiting or Intolerable Treatment Related Adverse Events (AEs)
timeFrame: Day 1 to Day 85
measure: Percentage of Participants With All-Causality AEs by Grade
timeFrame: Day 1 to Day 85
measure: Percentage of Participants With Treatment-Related AEs by Grade
timeFrame: Day 1 to Day 85
measure: Number of Participants With Any Laboratory Abnormality
timeFrame: Day 1 to 85
measure: Median Change From Baseline in Platelets and White Blood Cell [WBC] Count (With Differentials) at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Red Blood Cell (RBC) Count at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Hematocrit at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Hemoglobin, Total Protein, and Albumin at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Select Clinical Chemistry Parameters at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Sodium, Potassium, Chloride, and Bicarbonate at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Liver Function Tests at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Thyroid-Stimulating Hormone (TSH) at Last Observation
timeFrame: Baseline, Last observation (up to Day 85)
measure: Median Change From Baseline in Serum Creatine Kinase (CK), Amylase, and Lipase at Last Observation
timeFrame: Baseline, Last Observation (up to Day 85)
measure: Median Change From Baseline in Free Triiodothyronine (T3) and Free Thyroxine (T4) at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in T4 at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Urine WBC at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Median Change From Baseline in Urine pH at Last Observation
timeFrame: Baseline, last observation (up to Day 85)
measure: Number of Participants With Abnormal and Clinically Relevant Changes in Blood Pressure
timeFrame: Day 1 up to 85
measure: Number of Participants With Abnormal and Clinically Relevant Changes in Electrocardiogram (ECG) Parameters
timeFrame: Day 1 up to 85
measure: Number of Participants With Positive Anti-Drug Antibodies (ADAs) by Study Visit
timeFrame: Days -1, 8, 15, 29, 43, 57, and 85
Secondary outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Clearance (CL)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Terminal Elimination Half-Life (t1/2)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)]
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Day 1 prior to infusion, 1, 2, 4, 8 and 12 hours and anytime on Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85 post-infusion
measure: Percentage Change From Baseline in Total Dickkopf-1 (DKK-1) Concentrations Over Time
timeFrame: Day -1, Day 1 (predose and at end of infusion) and at 2, 4, 8, and 12 hours postdose, and Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57, and 85
measure: Mean Percentage Change From Baseline in Serum Procollagen Type 1 Amino-Terminal Propeptide (PINP) (ng/mL) Over Time
timeFrame: Baseline (Days -1, 1), Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
measure: Mean Percentage Change From Baseline in Serum n-Terminal Telopeptide(NTX) Over Time
timeFrame: Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
measure: Mean Percentage Change From Baseline in Serum Carboxy (C) Terminal Telopeptide (CTX) Over Time
timeFrame: Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
measure: Mean Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) Over Time
timeFrame: Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
measure: Mean Percentage Change From Baseline in Serum Osteocalcin Over Time
timeFrame: Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
measure: Mean Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85
timeFrame: Days -1 and 85
measure: Femoral Neck BMD at Day 85
timeFrame: Day 85
measure: Femoral Neck T-Score at Day 85
timeFrame: Day 85
measure: Mean Percentage Change From Baseline in Distal Radius BMD at Day 85
timeFrame: Baseline (Day -1), Day 85
measure: PK/PD Model Describing the Relationship Between PF-04840082 PK Parameter Estimates/Concentrations and Changes in PD Endpoints
timeFrame: Day 1 to Day 85
Other outcomes:
Locations:
city: Coral Gables
country: United States
facility: Ambulatory Diagnostic Center
state: Florida
city: Coral Gables
country: United States
facility: Gable Diagnostics
state: Florida
city: Coral Gables
country: United States
facility: Gables Diagnostics
state: Florida
city: Miami
country: United States
facility: SeaView Research, Inc.
state: Florida
city: Miami
country: United States
facility: SeaView Research, Inc.
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: South Miami
country: United States
facility: MRA Clinical Research
state: Florida
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: