A Multicenter, Open-label, Dose Ranging Study to Determine the Pharmacokinetics and Pharmacodynamics of Mepolizumab Administered Intravenously or Subcutaneously to Adult Asthmatic Subjects With Elevated Blood Eosinophil Levels

NCT01366521 Phase 2 COMPLETED Results posted

A multi-center, randomized, open-label, parallel-group, repeat dose study in asthma patients with elevated eosinophils. Eligible subjects will receive 3 doses (28 days apart) of mepolizumab given intravenous (IV) or subcutaneously (SC). Blood samples for safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity analysis, as well as safety/tolerability assessments will be collected throughout the study

Details

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	COMPLETED
Enrolment	70
Start date	2011-02
Completion	2012-03

Conditions

• Asthma

Interventions

• Mepolizumab

Primary outcomes

• Change From Baseline in Blood Eosinophil Levels at Week 12 (Day 84) — Baseline (Day 1 pre-dose) and Week 12
  Change from Baseline in blood eosinophils was calculated as the post-Baseline value minus the Baseline value. The change from Baseline in log-transformed blood eosinophil levels at Week 12 was analyzed using both a linear and non-linear (Imax) dose response models. The dose response was found to be non-linear and hence only the results of the non-linear model are presented. Mepolizumab 75mg IV assumed to equate to 100 mg SC within model. Prior to log10-transformation, zero values were imputed with half the minimum value across all dose groups and time points. An adjustment for Baseline eosinophil count was also incorporated into the model.
• Area Under the Blood Eosinophil Time Curve (AUEC) up to Day 84 — Days 1, 3, 7, 28, 56, 70 and 84
  Area under the absolute blood eosinophil time curve to Day 84 (AUECeos\[0-day 84\]) determined using the linear trapezoidal rule for subset of participants with blood eosinophil data to Day 84. Blood samples for the analyses of AUEC(eos) (0-day 84) were collected at Days 1, 3, 7, 28, 56, 70 and 84.
• Maximum Change From Baseline in Blood Eosinophils (Emax) — Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
  Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 to assess the maximum reduction from Baseline in blood eosinophils between Day 1 pre-dose and last quantifiable study measurement. Change from Baseline was calculated as the ratio of the post-Baseline value divided by the Baseline value. The maximum reduction from Baseline in eosinophils is represented by the minimum ratio to Baseline.
• Time to Maximum Change in Blood Eosinophils Levels (Tmaxeos) — Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
  Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 to assess the time to first occurrence of maximum reduction from baseline in blood eosinophil levels between Day 1 pre-dose and last quantifiable study measurement.
• Number of Participants Who Achieved >=50% Eosinophil Repletion by Day 140 — Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
  This summarizes the number of participants who returned to at least 50% of their Baseline blood eosinophil levels after maximum inhibition had been achieved and without any subsequent decrease in blood eosinophil levels. Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140.
• Mean Area Under the Plasma-concentration Time Curve (AUC) Following SC and IV Administration of Mepolizumab — Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
  AUC of mepolizumab was estimated by population modeling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Individual cumulative plasma of mepolizumab AUC to Day 84 (cumAUC(0-day 84)), is the sum of the AUCs over each dosing interval after each of the three doses administered, for those participants with data up to Day 84. Individual cumulative plasma of mepolizumab AUC to Day 140 (cumAUC(0-day 140) is the sum of the AUCs over each dosing interval after each of the three doses administered plus the AUC post the last dose interval up to Day 140 (i.e. from Day 84 to Day 140). Blood samples for PK analyses were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 hour (h), 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).

Countries

United States, Estonia, France, Germany