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Drug/Drug Interactions With F901318

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ClinicalTrials.gov Identifier: NCT03095547
Recruitment Status : Withdrawn (study no longer required in current format)
First Posted : March 29, 2017
Last Update Posted : November 1, 2017
Sponsor:
Collaborator:
Bio-Kinetic Europe, Ltd.
Information provided by (Responsible Party):
F2G Ltd.

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.


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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Aspergillosis

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




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



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03095547


Sponsors and Collaborators
F2G Ltd.
Bio-Kinetic Europe, Ltd.
Investigators
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Principal Investigator: David Bell, MD BioKinetic Europe

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Responsible Party: F2G Ltd.
ClinicalTrials.gov Identifier: NCT03095547     History of Changes
Other Study ID Numbers: F901318-01-11-17
First Posted: March 29, 2017    Key Record Dates
Last Update Posted: November 1, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Aspergillosis
Mycoses
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
Hormones, Hormone Substitutes, and Hormone Antagonists