title: Pharmacokinetic drug-drug interaction assessment of peptibody trebananib in combination with chemotherapies.
abstract: OBJECTIVE
  To provide the first evaluation of pharmacokinetic (PK) drug-drug interactions (DDIs) between trebananib and chemotherapies across tumor types.
  
  
  METHODS
  PK data of trebananib and chemotherapies (paclitaxel, carboplatin, pegylated liposomal doxorubicin, topotecan, capecitabine, lapatinib, 5-FU, irinotecan, or docetaxel) were collected from trials of ovarian cancer, metastatic breast cancer, colorectal carcinoma, and mixed solid tumor. A dedicated PK DDI study of trebananib and paclitaxel in patients with mixed solid tumors was also conducted. The geometric least squares mean (GLSM) ratios and corresponding 90 % confidence intervals (CI) of C max and AUC were estimated for DDI evaluations.
  
  
  RESULTS
  In the PK DDI study of trebananib and paclitaxel, the GLSM ratio (90 % CI) was 1.17 (1.10-1.25) for paclitaxel AUC and 1.30 (1.15-1.48) for paclitaxel C max. The GLSM ratio (90 % CI) for the effect of paclitaxel on trebananib PK was 0.92 (0.87-0.97) for trebananib AUC and 0.98 (0.92-1.05) for trebananib C max. In the remaining studies, the GLSM ratios (90 % CI) of C max and AUC generally ranged from 0.8 to 1.25 or exhibited less than twofold PK variabilities across chemotherapeutic agents. No dose-dependent DDIs were evident.
  
  
  CONCLUSIONS
  No PK DDI was deemed clinically meaningful between trebananib and the tested chemotherapeutic agents to warrant dose adjustments.
authors.affiliation: Clinical Pharmacology, Modeling and Simulations Group, Department of Medical Sciences, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91310, USA, wub@amgen.com.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.forename: Rebeca
authors.initials: R
authors.lastname: Melara
authors.forename: Erik
authors.initials: E
authors.lastname: Rasmussen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Teresa
authors.initials: T
authors.lastname: Wong
authors.forename: Cindy
authors.initials: C
authors.lastname: Kitahara
authors.forename: Mark
authors.initials: M
authors.lastname: Ma
authors.forename: Jessica
authors.initials: J
authors.lastname: Lu
authors.forename: Erick
authors.initials: E
authors.lastname: Gamelin
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Pickett
authors.forename: Yu-Nien
authors.initials: YN
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004347:Drug Interactions; D006801:Humans; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D017239:Paclitaxel; C551398:trebananib