PK, PD, Safety and Tolerability of Lipegfilgrastim in Healthy Japanese and Caucasian Participants

NCT02306915 | Completed Phase 1 DMC

• 1 other identifier: XM22-PK-10036
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Cohorts of Japanese participants will be enrolled and treated prior to cohorts of Caucasian participants for the sake of matching. Every effort will be made to match Caucasian and Japanese participants on a cohort basis at enrollment. Reasonable effort will be made to maintain balance between male and female participants within the cohorts. There will be no replacement of participants following randomization.

Conditions

Pharmacokinetics; Pharmacodynamics

Keywords

Lipegfilgrastim, Lonquex, Japanese Bridging

Outcome Measures

Primary Outcomes (17)

• PK: Area under the serum concentration-time curve (AUC), from time 0 to the last measurable concentration (AUC0-t)

  2 hours for visits 3, 9; 1 day for visit 10

  Days 1-8, 10, 14, 17, 21

• AUC from time 0 extrapolated to infinity (AUC0-∞)

  Days 1-8, 10, 14, 17, 21

• Maximum observed serum drug concentration (Cmax)

  Days 1-8, 10, 14, 17, 21

• Time to maximum observed serum drug concentration (tmax)

  Days 1-8, 10, 14, 17, 21

• The percentage of the extrapolated area to infinity in relation to the total area under the curve (%AUCext)

  Visits 3, 9, 10

• Apparent serum terminal elimination rate constant (λz)

  2 hours for visits 3, 9; 1 day for visit 10

  Days 1-8, 10, 14, 17, 21

• Associated elimination half-life (t½)

  Days 1-8, 10, 14, 17, 21

• Mean residence time (MRT)

  Days 1-8, 10, 14, 17, 21

• Apparent total body clearance (CL/F)

  Days 1-8, 10, 14, 17, 21

• Apparent volume of distribution during the terminal phase (Vz/F)

  Days 1-8, 10, 14, 17, 21

• PD: ANC area over baseline effect curve (ANC AOBEC)

  Days 1-8, 10, 14, 17, 21

• Maximum measured ANC value after dosing (ANC Cmax)

  Days 1-8, 10, 14, 17, 21

• Time point at which ANC Cmax is observed (ANC tmax)

  Days 1-8, 10, 14, 17, 21

• Time (days) until ANC returns to baseline value

  Days 1-8, 10, 14, 17, 21

• CD34+ area over the baseline effect curve (CD34+ AOBEC)

  Days 1-8, 10, 14, 17, 21

• Maximum measured CD34+ value after dosing (CD34+ Cmax)

  Days 1-8, 10, 14, 17, 21

• Time point at which CD34+ Cmax is observed (CD34+ tmax)

  Days 1-8, 10, 14, 17, 21

Secondary Outcomes (1)

• Percentage of Participants with Adverse Events

  28 Days

Study Arms (3)

lipegfilgrastim 30

EXPERIMENTAL

Drug: lipegfilgrastim

lipegfilgrastim 60

EXPERIMENTAL

Drug: lipegfilgrastim

lipegfilgrastim 100

EXPERIMENTAL

Drug: lipegfilgrastim

Interventions

lipegfilgrastim DRUG

lipegfilgrastim 30 μg/kg, 60 μg/kg, 100 μg/kg

lipegfilgrastim 100; lipegfilgrastim 30; lipegfilgrastim 60

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) ≥18.0 and ≤25 kg/m2.
• Body weight must be ≥ 50 kg and ≤ 90 kg.
• Is in good general health as determined by medical history, physical examination, 12-lead electrocardiography (ECG), vital signs and clinical laboratory tests.
• Subjects are able to read, write and understand English or Japanese; they must be able to understand the requirements of the study and be willing to comply with all trial requirements.
• Female subjects of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) test at screening and negative urine pregnancy test at check-in. All subjects must be either surgically sterile (for females that means documented complete hysterectomy, bilateral oophorectomyor bi-tubal ligations; partial hysterectomy is not sufficient), abstinent throughout the study or, if of reproductive capacity and not abstinent, exercising any 2 different forms of highly effective contraception methods with his/her partner during the entire study period.
• Subject must be a non-naturalized Japanese citizen and hold a Japanese passport.
• Subject must have/had 2 Japanese parents and 4 Japanese grandparents who are all non-naturalized Japanese citizens, as confirmed by interview.
• Subject has been living outside of Japan for 10 years or fewer as confirmed by interview.
• The subject is Caucasian, and confirms by interview that his/her parents and grandparents are Caucasian and none are of Black/African descent, Middle-Eastern descent or Asian descent.
• other criteria apply, please contact the investigator for more information

You may not qualify if:

• History of hypersensitivity to pegfilgrastim, filgrastim, lenograstim, Escherichia coli derived proteins, or to any excipients (glacial acetic acid, sodium hydroxide, sorbitol, polysorbate 20).
• Prior exposure to filgrastim, pegfilgrastim or lenograstim or other granulocyte colony stimulating factors (G-CSFs) in clinical development less than 6 months before randomization.
• Findings of splenomegaly on sonography, defined by splenic length in excess of 12.3 cm (Andrews, 2000; Benter et al, 2011) and clinical judgment.
• Existence or recent history of persistent pulmonary infiltrates or recent pneumonia, or current symptoms of upper respiratory infection. In the case of pneumonia, subject may be screened 12 weeks following cessation of antibiotic treatment.
• other criteria apply, please contact the investigator for more information

Sponsors & Collaborators

• Merckle GmbH: lead

Study Sites (1)

Teva Investigational Site 34193

London, United Kingdom

Location

MeSH Terms

Interventions

pegfilgrastim

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 3, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 9, 2021

Record last verified: 2021-11

Locations

GB (1)