Drug/Drug Interactions With F901318

• ClinicalTrials.gov Identifier: NCT03095547
• Recruitment Status: Withdrawn
• First Posted: March 29, 2017
• Last Update Posted: November 1, 2017
• Sponsor: F2G Biotech GmbH
• Collaborator: Bio-Kinetic Europe, Ltd.
• Information provided by (Responsible Party): F2G Biotech GmbH

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Invasive Aspergillosis	Drug: cyclosporine A; Drug: Posaconazole; Drug: Pantoprazole; Drug: F901318; Drug: Tacrolimus	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Three arm parallel group evaluation with fourth arm in series
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: May 2017
• Estimated Primary Completion Date: July 2017
• Estimated Study Completion Date: October 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: F901318 & cyclosporine A & tacrolimus; Interaction between cyclosporine A and tacrolimus with F901318	Drug: cyclosporine A; Pharmacokinetic assessment Area Under the plasma concentration: time Curve (AUC) 0-t; Drug: F901318; Pharmacokinetic assessment AUC 0-tau; Drug: Tacrolimus; Pharmacokinetic assessment AUC 0-t
Experimental: F901318 & posaconazole; Interaction between posaconazole and F901318	Drug: Posaconazole; Pharmacokinetic assessment AUC 0-tau; Drug: F901318; Pharmacokinetic assessment AUC 0-tau
Experimental: F901318 & pantoprazole; Interaction between pantoprazole and F901318	Drug: Pantoprazole; Pharmacokinetic assessment AUC 0-tau; Drug: F901318; Pharmacokinetic assessment AUC 0-tau
Experimental: F901318; F901318 alone	Drug: F901318; Pharmacokinetic assessment AUC 0-tau

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics: Area under curve 0-t [ Time Frame: 21 days ]
   Area under curve 0-t

Secondary Outcome Measures :

1. Tolerability: Adverse events [ Time Frame: 21 days ]
   Adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Subjects will be males and females of any ethnic origin between 18 and 55 years of age and weighing between 60 and 100 kg inclusive.
2. Subjects must be in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations
3. Hepatic transaminases must be within normal limits but congenital non haemolytic hyperbilirubinaemia is acceptable.
4. Negative pregnancy test in all females of child bearing potential at screening and Day -1
5. Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions

Exclusion Criteria:

1. Female and male subjects who are not, or whose partners have not used for at least three months prior to screening and are not willing to use appropriate contraception during the study and for 3 months after end of dosing.
2. Pregnancy and lactation.
3. For cohort A only, clinically significant infection within the past 6 months or recurring herpes infections within the past 6 months or history of tuberculosis
4. Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration unless in the opinion of the Investigator and the medical monitor the medication will not interfere with the study procedures or compromise safety
5. Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the dose administration (with the exception of vitamin/mineral supplements) unless in the opinion of the Investigator and the medical monitor the medication will not interfere with the study procedures or compromise safety

Contacts and Locations

Sponsors and Collaborators

F2G Biotech GmbH

Bio-Kinetic Europe, Ltd.

Investigators

• Principal Investigator: David Bell, MD; BioKinetic Europe

More Information

• Responsible Party: F2G Biotech GmbH
• ClinicalTrials.gov Identifier: NCT03095547
• Other Study ID Numbers: F901318-01-11-17
• First Posted: March 29, 2017
• Last Update Posted: November 1, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Cyclosporine; Posaconazole; Olorofim; Pantoprazole; Tacrolimus; Cyclosporins; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Trypanocidal Agents; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists