Clinical trial NCT03756922: A DDI Study of FDL169 and FDL176 in Healthy Subjects
Official title: A Phase 1/2, Drug-Drug Interaction Study of FDL169 and FDL176 in Healthy Subjects and in Cystic Fibrosis Subjects Homozygous for the F508del-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Lead sponsor: Flatley Discovery Lab LLC
Sponsor class: OTHER
First posted: 2018-11-28
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Parallel for Part 1 and Part 2; Sequential for Part 3 and Part 4
Primary purpose: TREATMENT

Brief summary: A DDI study to assess the safety, tolerability and pharmacokinetics of both; doses of FDL176 with and without co-administration of FDL169 and doses of FDL169 with and without co-administration of FDL176.

Detailed description: This is an open-label, non-randomised study. Enrolment will be in two parallel and independent parts. Part 1 will assess the safety, tolerability and pharmacokinetics of single doses of FDL176 with and without co-administration of FDL169. Part 2 will assess the safety, tolerability and pharmacokinetics of repeated doses of FDL169 with and without co-administration of FDL176.

Eligibility criteria: Inclusion Criteria:

* Healthy males or non-pregnant, non-lactating healthy females
* Body mass index of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
* Must agree to follow the study's contraception requirement

Exclusion Criteria:

* Prior or ongoing medical condition, medical history, physical findings, ECG findings or laboratory abnormality that, in the Investigator's (or delegate's) opinion, could adversely affect the safety of the subject or would place the subject at increased risk.
* History of long QT syndrome and/or QT corrected according to Fridericia's formula (QTcF) interval (\>450 msec) or QTcF \>450 msec at Screening or Day -1.
* Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active.
* Use of any prescription drugs within 14 days or 5 half-lives (whichever is longer) before the first dose of IMP.
* Use of any non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) before the first dose of IMP.
* Use of any prescription and non-prescription medications that are strong inhibitors or moderate inducers of cytochrome P450 3A, within 14 days or 5-half-lives (whichever is longer) before the first dose of IMP. Use of any prescription and non-prescription medications that are strong inducers of cytochrome P450 3A within 28 days before the first dose of IMP.
* Participation in another clinical trial involving receipt of an IMP within the past 90 days.
* Prior exposure to FDL169 or FDL176
* Alkaline phosphatase, aspartate aminotransferase and/or alanine aminotransferase \>1.5 x upper limit of normal (ULN) at screening.
* Serum creatinine or total bilirubin \>1.5 x ULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%).
* Abnormal renal function at screening, defined as estimated glomerular filtration rate \<60 mL/min using the Modification of Diet in Renal Disease (MDRD) equation.
* History of human immunodeficiency virus (HIV) or positive HIV, hepatitis B or hepatitis C results at screening.
* Positive urinary drugs of abuse screen at Screening or Day -1, or positive alcohol breath test at Screening or Day -1. Consumption of alcohol within 24 h prior to admission.
* Consumption of any food or drink containing grapefruit, or Seville oranges (including marmalade and fruit juices) for 14 days before the first dose of IMP.
* Consumptions or foods containing poppy seeds or involvement in strenuous exercise for 3 days before admission.
* Known hypersensitivity to any component of the formulation of FDL169 or FDL176.
* Pregnant or nursing females.
* History of regular alcohol consumption within 6 months of the study
* Current smoking or use of tobacco products or substitutes.
* Poor peripheral venous access.
* Donation of ≥470 mL blood or loss of blood during surgery or due to trauma within 3 months prior to Day 1.
* Plasma donation within 7 days prior to Day 1.
* Failure to satisfy the Investigator of their fitness to participate for any other reason.
* Site staff, Sponsor staff or first degree family members of site or Sponsor.

Primary outcomes:
measure: Pharmacokinetic parameters, Cmax
timeFrame: Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Celerion GB Ltd
Study officials:
References: