Clinical Trial: Study on Safety and Pharmacokinetics of Intravenous F901318 for Fungal Prophylaxis in AML Patients

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: An Open Label Phase IIa Clinical Study to Evaluate the Safety and Pharmacokinetics of Intravenous and Oral F901318 (Combined With Caspofungin) for Antifungal Prophylaxis in Patients Undergoing Chemoth

Brief Summary: This study assesses the pharmacokinetics and safety of the new antifungal F901318 in AML patients.

Detailed Summary:

F901318 has potent in vitro efficacy against Aspergillus spp. including azole-resistant strains and consistent efficacy in in vivo mouse models of infection. F901318 is active by both oral and intravenous routes of administration in preclinical efficacy studies.

Non-clinical studies and phase I clinical trials show that F901318 has a good overall safety profile and limited potential for drug-drug interactions. F901318 exhibits a highly promising profile which can potentially address the critical treatment requirements for invasive Aspergillus infections in a changing clinical environment in which new classes of antifungals are needed.

This phase IIa study aims to confirm PK and safety information of F901318 from phase I and bridge them to a neutropenic AML patient population, which represents the main population for future efficacy trials. Coadministration of caspofungin will allow recognizing potential factors of suboptimal F901318 exposure without the risk of fatal disseminating infection.


Sponsor: F2G Ltd.

Current Primary Outcome: Collection of adverse events, results of physical examination, vital signs, ECGs, and laboratory assessments during F901318 intravenous infusion and oral formulation. [ Time Frame: 57 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Concentration-time profile of F901318 following i.v. administration [ Time Frame: 14 days ]
    F901318 trough level assessment for 14 days once per day. On three of these 14 days additional samples for determination of plasma concentration of F901318 will be collected.
  • Measured concentration of F901318 at the end of an i.v. dosing interval at steady state (Ctrough) [ Time Frame: 14 days ]
  • Minimum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmin, ss) [ Time Frame: 14 days ]
  • Maximum observed plasma or serum, concentration of F901318 during an i.v. dosing interval at steady state (Cmax, ss) [ Time Frame: 14 days ]
  • Average plasma or serum concentration of F901318 at steady state after i.v. administration (Cav,ss) [ Time Frame: 14 days ]
  • Area under the concentration-time curve during a F901318 i.v. dosing interval at steady state calculated by trapezoidal rule (AUCT,ss) [ Time Frame: 14 days ]
  • Area under the concentration vs. time curve from point zero up to the end of infusion of F901318 (AUC(0-T)) [ Time Frame: 14 days ]
    T: total time of infusion
  • Area under the concentration vs. time curve from time point zero up to the time point t (AUC(0-t)) for F901318 after i.v. administration [ Time Frame: 14 days ]
  • Area under the concentration vs. time curve from time point zero up to the last measured concentration of F901318 above LOQ (AUC(0-t_last)) after i.v. administration [ Time Frame: 14 days ]
  • Apparent terminal half-life (t1/2) of F901318 after i.v. administration [ Time Frame: 14 days ]
  • Terminal rate constant (λz) of F901318 after i.v. administration [ Time Frame: 14 days ]
  • Apparent clearance (Cl) of F901318 after i.v. administration [ Time Frame: 14 days ]
  • Plasma concentration of F901318 after oral application [ Time Frame: 1 day ]
    Measurement 2h, 4h, 12h and 24h after oral intake of F901318
  • Number of patients developing an possible/probable/proven invasive fungal disease (IFD) according to EORTC/MSG criteria [ Time Frame: 57 days ]
    Patients galactomannan index and body temperature will be assessed regularly. If it is clinically indicated the patients will undergo a CT, which will be checked for infiltrations. If infiltrations are detected the patients will undergo a bronchoalveolar lavage, the result of which will be used to analyse BAL GMI, to grow a microbiological culture, to perform histology and perform an Aspergillus PCR. On the basis of the available data for each patient the scientific advisory committee will assess the number of patients suffering from a possible/probable or proven IFD.


Original Secondary Outcome: Same as current

Information By: F2G Ltd.

Dates:
Date Received: July 14, 2016
Date Started: September 2016
Date Completion: May 2017
Last Updated: August 1, 2016
Last Verified: August 2016