The purpose of this study is to determine the safety and tolerability of RN564 in women with osteopenia and healthy men.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
68
Intravenous, single dose with experimental dose
Ambulatory Diagnostic Center
Coral Gables, Florida, United States
Gable Diagnostics
Coral Gables, Florida, United States
Gables Diagnostics
Coral Gables, Florida, United States
SeaView Research, Inc.
Miami, Florida, United States
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.
Time frame: 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.
Time frame: 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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
SeaView Research, Inc.
Miami, Florida, United States
Miami Research Associates
Miami, Florida, United States
MRA Clinical Research
South Miami, Florida, United States
Vince and Associates Clinical Research
Overland Park, Kansas, United States
Time frame: 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.
Time frame: 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)
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Red Blood Cell (RBC) Count at Last Observation
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Hematocrit at Last Observation
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Hemoglobin, Total Protein, and Albumin at Last Observation
Time frame: 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
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Sodium, Potassium, Chloride, and Bicarbonate at Last Observation
Time frame: 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
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Thyroid-Stimulating Hormone (TSH) at Last Observation
Time frame: Baseline, Last observation (up to Day 85)
Median Change From Baseline in Serum Creatine Kinase (CK), Amylase, and Lipase at Last Observation
Time frame: Baseline, Last Observation (up to Day 85)
Median Change From Baseline in Free Triiodothyronine (T3) and Free Thyroxine (T4) at Last Observation
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in T4 at Last Observation
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Urine WBC at Last Observation
Time frame: Baseline, last observation (up to Day 85)
Median Change From Baseline in Urine pH at Last Observation
Time frame: 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).
Time frame: 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.
Time frame: Day 1 up to 85
Number of Participants With Positive Anti-Drug Antibodies (ADAs) by Study Visit
Time frame: Days -1, 8, 15, 29, 43, 57, and 85
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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Days -1 and 85
Femoral Neck BMD at Day 85
BMD was evaluated by dual energy X-ray absorptiometry (DXA).
Time frame: 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.
Time frame: Day 85
Mean Percentage Change From Baseline in Distal Radius BMD at Day 85
BMD was evaluated by DXA.
Time frame: 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.
Time frame: Day 1 to Day 85