Drug/Drug Interactions With F901318

Invasive Aspergillosis Clinical Trial

Official title: An Open Label Assessment of the Effect of Coadministration of Posaconazole or Pantoprazole on Systemic Exposure of F901318 and the Effect of F901318 on the Single Dose Pharmacokinetics of Tacrolimus and Cyclosporine A in Healthy Male and Female Subjects

Status Withdrawn

Clinical Trial Summary

Study of interactions between F901318 and multiple doses of posaconazole and pantoprazole and single doses of cyclosporine A and tacrolimus in healthy subjects. Pharmacokinetic (PK) profiles, safety and tolerability will be assessed.

Clinical Trial Description

Open label randomised parallel group evaluation of three or four dosing schedules over a period of 21 days. Subjects will be randomised into the groups as follows:

1. Cohort A: Pre-treat with tacrolimus 2 mg on day -9 and cyclosporine A 100 mg on Day -3 and obtain pharmacokinetic (PK) curves for both compounds prior to dosing with F901318. Then, F901318 360 mg b.i.d. for 1 or two days followed by 240 mg b.i.d. for 18 or 19 days (Days 2 or 3-20) and 240 mg o.m. on Day 21 (n=12, ideally 6 females minimum 3 females, 6 males, maximum 9 males). Dose again with tacrolimus on Day 9 and with cyclosporine A on day 16 and obtain full PK curves.

2. Cohort B: F901318 360 mg b.i.d. for 1 or 2 days followed by 240 mg b.i.d. for 5 or 6 days. On Day 8, add posaconazole tablets 300 mg b.i.d. followed by 300 mg daily for 6 days (Days 9-14) and decrease F901318 dose to 120 mg daily from Day 8 onwards. On Day 15, discontinue posaconazole but continue F901318 for a further 6 days at a dose of 120 mg daily (Days 15 to 21) (n=12, ideally 6 females, 6 males).

3. Cohort C: F901318 360 mg b.i.d. for one or two days followed by 240 mg b.i.d for 19 days (Day 1-20) and 240 mg o.m. on Day 21. On Day 8, add pantoprazole 40 mg daily for 7 days. On Day 15, discontinue pantoprazole but continue F901318 240 mg b.i.d to day 20 and 240 mg o.m. on Day 21 (n=12, ideally 6 females, 6 males).

4. Cohort D (optional): F901318 for 21 days. Will be conducted, if necessary after completion of cohorts A-C. Dose schedule to be determined on the basis of results from ongoing study F901318-01-06-16 and cohort A of this study but could be up to 480 mg b.i.d for up to three days followed by up to 360 mg bid for 17-19 days and up to 360 o.m. on Day 21 with the objective of achieving and maintaining C12 of 1µg/mL throughout the dosing period (n=12, ideally 6 females, 6 males). The decision to proceed will be taken based on QC'd pharmacokinetic data by the PI and representative(s) of the Sponsor.

Intensive PK evaluations of F901318 and metabolite and concomitant medications will occur as follows:

• Day 1 (F901318 and metabolite alone)

• Day 7 (F901318 and metabolite alone)

• Day 14 (F901318 and metabolite and posaconazole cohort B)

• Day 21 (F901318 and metabolite)

Peak and trough levels of F901318 and metabolite (and posaconazole in cohort B on Days 8-20) will be obtained on intermediate days.

PK curves for tacrolimus will be obtained from Day -9 to Day -3 and from Day 9 to Day 15 (cohort A)

PK curves for cyclosporine A will be obtained from Day -3 to Day 1 (prior to dosing with F901318) and from Day 18 to Day 21 (cohort A)

Adverse events and 12 lead ECGs will be recorded and blood and urine samples will be obtained for safety evaluation throughout.

All subjects will return for a post-study visit 8 to 10 days after the last dose of study medication. ;

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Aspergillosis

• NCT number: NCT03095547
• Study type: Interventional
• Source: F2G Ltd.
• Status: Withdrawn
• Phase: Phase 1
• Start date: May 2017
• Completion date: October 2017