Healthy Volunteers
Conditions
Keywords
Pegfilgrastim, G-CSF, Pharmacokinetics, Pharmacodynamics
Brief summary
This is a single center, double-blind, randomized, comparative pharmacokinetic and pharmacodynamic study of MYL-1401H and Neulasta (from EU and US source) in Normal Healthy Volunteers.
Detailed description
After successful screening, each subjects will be randomly allocated to one of the following six possible sequences, according a 1:1:1:1:1:1 randomization scheme: Sequence\_1: Treatment A -\> Treatment B -\> Treatment C ; Sequence\_2: Treatment A -\> Treatment C -\> Treatment B ; Sequence\_3: Treatment B -\> Treatment A -\> Treatment C ; Sequence\_4: Treatment B -\> Treatment C -\> Treatment A ; Sequence\_5: Treatment C -\> Treatment A -\> Treatment B ; Sequence\_6: Treatment C -\> Treatment B -\> Treatment A ; In study Period 1, Subjects will be administered MYL-1401H (Treatment A), EU-Neulasta(Treatment B) or US-Neulasta (Treatment C). After the 1st crossover, subjects will enter Study period 2 and will receive one of the remaining alternate treatments. After the 2nd crossover, subjects will enter Study period 3 and will receive the other alternate treatment. The washout between drug administrations is at least 4 weeks. Final follow-up visit is scheduled 4 weeks after the last study drug administration.
Interventions
Sponsors
Mylan GmbH
Mylan Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Weight: ≥60 kg. * Body mass index (BMI): 19.0-30.0 kg/m2 * Vital signs showing no clinically relevant deviations. * Computerized 12-lead ECG recording without signs of clinically relevant pathology. * Non-smoker or light smoker * Ability and willingness to abstain from alcohol from 48 hours prior to each admission to the clinical research center and prior to ambulatory visits, and during the stays in the clinic. * Fertile males and females participating in heterosexual sexual relations: willingness to use adequate contraception from screening until 90 days after the follow up visit * Females must not be lactating and must have a negative pregnancy test at screening and each admission. * ANC, total leukocyte count, platelet count, hematocrit and hemoglobin results within the reference ranges. * All other values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Principal Investigator Other protocol specific inclusion/
Exclusion criteria
may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics: Area under the curve above baseline of ANC [ANC_AUC(0-tlast)] | Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), and on Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29 | — |
| Pharmacodynamics: Maximum change from baseline in absolute neutrophil count (ANC); ANC_Cmax | Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29 | — |
| Area under the serum concentration-time curve (AUC0-inf) of Pegfilgrastim | Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29 | Pharmacokinetics as measured by total AUC after extrapolation from time t to time infinity |
| Maximum Serum Concentration (Cmax) of pegfilgrastim | Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29 | Pharmacokinetics as measured by peak serum concentration of Pegfilgrastim |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events | Daily until Day 9, then on Day 12, 15, 22 of each study period, and at follow-up visit (day 84). | Safety as measured by incidence of Adverse Events |
| Safety Variable - Tolerability as measured by Injection Site reactions | Daily until Day 5 of each period | Tolerability as measured by Injection Site reactions |
| Safety Variable - Immunogenicity as measured by presence of Anti Drug Antibodies | Day 1 each period and at follow-up (Day 84) | Immunogenicity as measured by presence of Anti Drug Antibodies |
Countries
Netherlands
Outcome results
None listed