An Open-Label, Single Dose Pharmacokinetic Study of Benefix (Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B

Phase 1

Completed

• Conditions: Hemophilia B
• Interventions: Drug: BENEFIX

• Registration Number: NCT02213250
• Lead Sponsor: Pfizer

Brief Summary

The sample size of 12 male Chinese subjects are based on the CFDA requirement for a China PK study and to support the registration in China.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-08-07
• Study First Submitted QC: 2014-08-07
• Study First Posted: 2014-08-11
• Study Start: 2015-03
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Results First Submitted: 2016-05-04
• Status Verified: 2016-06
• Results First Submitted QC: 2016-06-13
• Last Update Submitted: 2016-06-13
• Results First Posted: 2016-07-25
• Last Update Posted: 2016-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

• Male Chinese subjects 6 years or older (weight ≥20kg) with moderate to severe hemophilia B (Factor IX activity ≤2%).
• Subjects should not have received an infusion of any Factor IX products for at least 4 days before the administration of BeneFIX on Day 1.
• Subjects must be in a non-bleeding state before the administration of BeneFIX on Day 1.

Exclusion Criteria

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease or clinical findings at Screening.
• Diagnosed with any other bleeding disorder in addition to hemophilia B.
• Current FIX inhibitor or history of FIX inhibitor (defined as > Upper Limit of Normal (ULN) of the reporting lab).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BeneFIX	BENEFIX	-

Primary Outcome Measures

Name	Time	Method
Systemic Clearance (CL)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose	CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Maximum Observed Plasma Concentration (Cmax)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
Area Under the Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
Area Under the Concentration Time Curve From Time 0 to Infinity (AUCinf)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
Time to Reach Cmax (Tmax)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
Plasma Decay Half-Life (t½)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Incremental Recovery	Pre-dose, 0.25, 0.5 and 1 hour post-dose	Incremental recovery: Increase in circulating increase in FIX activity for every IU of BeneFIX administered per kg of body weight.
Volume of Distribution at Steady State (Vss)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose	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. Vss is the apparent volume of distribution at steady-state.
Terminal Phase Rate Constant (Kel)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose	Linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.
Mean Residence Time (MRT)	Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose	AUMCinf/AUCinf, where AUMCinf is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Withdrawals Due to Adverse Events (AE)	From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAE is defined as newly occurring or worsening after first dose.
Number of Participants With Vital Signs Post-Dose Data Met Criteria of Potential Clinical Concern (Without Regard to Baseline Abnormality)	Baseline up to 96 hours post-dose (Day 5 or early termination)
Number of Participants With Abnormal Clinical Laboratory Measurements (Without Regard to Baseline Abnormality)	Baseline up to 96 hours post-dose (Day 5 or early termination)	Clinical laboratory analysis tests included hematology, serium chemistry, prothrombin time and urianalysis. Numbers of subjects with laboratory test abnormalities without regard to baseline abnormality were reported.
Number of Participants With Inhibitor Development	From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.
Number of Participants With Allergic Reactions	From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.
Number of Subjects With Thrombogenicity	From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.

Trial Locations

Locations (2)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

Hematology Department,Beijing Children's Hospital, Capital Medical University; 🇨🇳 Beijing, China