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

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

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

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Osteopenia; Bone Disease
• Intervention / Treatment: Biological: RN564

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Ambulatory Diagnostic Center
    • Coral Gables, Florida, United States, 33134
      • Gable Diagnostics
    • Coral Gables, Florida, United States, 33134
      • Gables Diagnostics
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • Miami, Florida, United States, 33126
      • SeaView Research, Inc.
    • Miami, Florida, United States, 33134
      • SeaView Research, Inc.
    • South Miami, Florida, United States, 33143
      • MRA Clinical Research
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Biological: RN564; Intravenous, single dose with experimental dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-Limiting or Intolerable Treatment Related Adverse Events (AEs)	Dose-limiting or intolerable treatment related AEs was defined as any of the following criteria occurred in 2 or more participants: Serious adverse events, Increased liver transaminases, Increased bilirubin (in absence of ALT/AST elevations, allergic / hypersensitivity reactions, vasculitis, Musculoskeletal pain, Increased serum creatinine, Diarrhea, enteritis or nausea, Prolongation of QTcF interval or any other criteria If considered appropriate by the Medical Monitor and Investigator. A dose level was also be considered intolerable if, in the judgment of the Investigator and Sponsor, the type, frequency, or severity of AEs becomes unacceptable.	Day 1 to Day 85
Percentage of Participants With All-Causality AEs by Grade	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.	Day 1 to Day 85
Percentage of Participants With Treatment-Related AEs by Grade	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Relatedness to drug was assessed by investigator.	Day 1 to Day 85
Number of Participants With Any Laboratory Abnormality	Criteria for abnormality: hematology: hemoglobin, hematocrit, red blood cell count: less than(<) 0.8*lower limit of normal (LLN); platelets: <0.5*LLN,>1.75*ULN, white blood cell count: <0.6*LLN, >1.5*ULN; lymphocytes, total neutrophils: <0.8*LLN, >1.2*ULN; eosinophils, basophils, monocytes: >1.2*ULN; coagulation: activated partial thromboplastin time, prothrombin, prothrombin international ratio: >1.1*ULN; liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN></0>1.2*ULN; renal function: blood urea nitrogen, creatinine: >1.3*ULN; uric acid: >1.2*ULN; electrolytes: sodium>1.05*ULN, potassium, chloride, calcium, bicarbonate: <0.9*LLN,>1.1*ULN; urinalysis: pH<4.5, >8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite; Other(glucose: <0.6*LLN,>1.5*ULN), urine casts, granular casts, hyaline casts>1 LPF; hormones: T4, T3, TSH<0.8*LLN.	Day 1 to 85
Median Change From Baseline in Platelets and White Blood Cell [WBC] Count (With Differentials) at Last Observation	Median change from baseline in platelets, WBC count, lymphocytes (absolute [Abs]), total neutrophils (Abs), basophils (Abs), eosinophils (Abs), and monocytes (Abs)	Baseline, last observation (up to Day 85)
Median Change From Baseline in Red Blood Cell (RBC) Count at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in Hematocrit at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in Hemoglobin, Total Protein, and Albumin at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in Select Clinical Chemistry Parameters at Last Observation	Includes median changes from baseline in total bilirubin, direct bilirubin, indirect bilirubin, blood urea nitrogen (BUN), creatinine, uric acid, calcium, magnesium, and glucose	Baseline, last observation (up to Day 85)
Median Change From Baseline in Sodium, Potassium, Chloride, and Bicarbonate at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in Liver Function Tests at Last Observation	Includes median changes in aspartate aminotransferase (AST), alanine aminotransferase (AST), gamma glutamyltransferase (GGT), and alkaline phosphatase	Baseline, last observation (up to Day 85)
Median Change From Baseline in Thyroid-Stimulating Hormone (TSH) at Last Observation		Baseline, Last observation (up to Day 85)
Median Change From Baseline in Serum Creatine Kinase (CK), Amylase, and Lipase at Last Observation		Baseline, Last Observation (up to Day 85)
Median Change From Baseline in Free Triiodothyronine (T3) and Free Thyroxine (T4) at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in T4 at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in Urine WBC at Last Observation		Baseline, last observation (up to Day 85)
Median Change From Baseline in Urine pH at Last Observation		Baseline, last observation (up to Day 85)
Number of Participants With Abnormal and Clinically Relevant Changes in Blood Pressure	Participants with maximum changes from baseline (defined as increases or decreases of greater than or equal to [≥]20 mmHg or ≥30 mmHg) in either standing or supine systolic blood pressure (SBP) or diastolic blood pressure (DBP) measured in millimeters mercury (mmHg).	Day 1 up to 85
Number of Participants With Abnormal and Clinically Relevant Changes in Electrocardiogram (ECG) Parameters	Participants with maximum changes from baseline (BSL) defined as: ≥25 to 50 percent (%) increase in maximum PR interval or QRS complex; increase from BSL of ≥30 milliseconds (msec) but <60 msec in corrected QT (QTc) interval or QTcF interval (QTc interval corrected using Fridericia's correction); or increase from BSL ≥60 msec in either QTc interval or QTcF interval.	Day 1 up to 85
Number of Participants With Positive Anti-Drug Antibodies (ADAs) by Study Visit		Days -1, 8, 15, 29, 43, 57, and 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	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
Maximum Observed Serum Concentration (Cmax)		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
Time to Reach Maximum Observed Serum Concentration (Tmax)		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
Volume of Distribution at Steady State (Vss)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.	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
Clearance (CL)	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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
Terminal Elimination Half-Life (t1/2)	Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.	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
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)]	AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf).	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
Apparent Volume of Distribution (Vz/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. Based on internal clinical pharmacology guidance on the most appropriate parameter calculations for this study design, data for Vz/F was not collected instead Vss was reported.	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
Percentage Change From Baseline in Total Dickkopf-1 (DKK-1) Concentrations Over Time		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
Mean Percentage Change From Baseline in Serum Procollagen Type 1 Amino-Terminal Propeptide (PINP) (ng/mL) Over Time	Baseline calculated as average of Day -1 and Day 1 prior to infusion of PF-04840082	Baseline (Days -1, 1), Days 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
Mean Percentage Change From Baseline in Serum n-Terminal Telopeptide(NTX) Over Time	Baseline calculated as average of Day -1 and Day 1 prior to infusion of PF-04840082	Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
Mean Percentage Change From Baseline in Serum Carboxy (C) Terminal Telopeptide (CTX) Over Time	Baseline calculated as average of Day -1 and Day 1 prior to infusion of PF-04840082	Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
Mean Percentage Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) Over Time	Baseline calculated as average of Day -1 and Day 1 prior to infusion of PF-04840082	Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
Mean Percentage Change From Baseline in Serum Osteocalcin Over Time	Baseline calculated as average of Day -1 and Day 1 prior to infusion of PF-04840082	Days -1, 1 (predose), 2, 3, 4, 5, 8, 15, 22, 29, 36, 43, 57 and 85
Mean Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Day 85		Days -1 and 85
Femoral Neck BMD at Day 85	BMD was evaluated by dual energy X-ray absorptiometry (DXA).	Day 85
Femoral Neck T-Score at Day 85	BMD was evaluated by DXA. T-score was calculated based on actual measured bone density value and is the standardized scores that reflect the standard deviations (SDs) above/below the mean. A BMD T-score of -1.0 or more indicates normal bone density. T-score between -1.0 and -2.5 indicates low bone density known as osteopenia. A T-score of -2.5 or less is diagnostic of osteoporosis.	Day 85
Mean Percentage Change From Baseline in Distal Radius BMD at Day 85	BMD was evaluated by DXA.	Baseline (Day -1), Day 85
PK/PD Model Describing the Relationship Between PF-04840082 PK Parameter Estimates/Concentrations and Changes in PD Endpoints	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 1 to Day 85

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): May 24, 2012
• Study Completion (Actual): May 24, 2012

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 9, 2011
• First Posted (Estimated): February 10, 2011

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Phase 1; Osteopenia; RN564
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Osteoporosis; Bone Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: B1151001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.