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

NCT01293487 | Completed Phase 1 Results

• 1 other identifier: B1151001
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Osteopenia; Osteoporosis; Bone Disease

Keywords

Phase 1; Osteopenia; RN564

Outcome Measures

Primary Outcomes (20)

• 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 Outcomes (19)

• Area Under the Curve From Time Zero to Last Quantifiable 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)

  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)

  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

Study Arms (1)

Arm 1

EXPERIMENTAL

Biological: RN564

Interventions

RN564 BIOLOGICAL

Intravenous, single dose with experimental dose

Arm 1

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (8)

Ambulatory Diagnostic Center

Coral Gables, Florida, 33134, United States

Location

Gable Diagnostics

Coral Gables, Florida, 33134, United States

Location

Gables Diagnostics

Coral Gables, Florida, 33134, United States

Location

SeaView Research, Inc.

Miami, Florida, 33126, United States

Location

SeaView Research, Inc.

Miami, Florida, 33134, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

Location

MRA Clinical Research

South Miami, Florida, 33143, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

Related Links

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

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis; Bone Diseases

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2011
• First Posted: February 10, 2011
• Study Start: April 1, 2011
• Primary Completion: May 24, 2012
• Study Completion: May 24, 2012
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)