A Drug-Drug Interaction Study of FDL169 and FDL176 in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT03516331
• Recruitment Status: Completed
• First Posted: May 4, 2018
• Last Update Posted: November 2, 2018
• Sponsor: Flatley Discovery Lab LLC
• Information provided by (Responsible Party): Flatley Discovery Lab LLC

Tracking Information

• First Submitted Date: April 24, 2018
• First Posted Date: May 4, 2018
• Last Update Posted Date: November 2, 2018
• Actual Study Start Date: March 7, 2018
• Actual Primary Completion Date: August 22, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2018)

Pharmacokinetic parameters, Cmax [ Time Frame: 72 days ]

The pharmacokinetic parameters of FDL176 when co-administered with FDL169, compared to the pharmacokinetics of FDL176 alone; maximal plasma concentration (Cmax)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2018)

Incidence of Treatment-Emergent Adverse Events [ Time Frame: 72 days ]

Safety and tolerability of FDL176 when co-administered with FDL169, compared to FDL176 alone. as determined by the incidence of adverse events (Aes) and serious adverse events (SAE)s.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Drug-Drug Interaction Study of FDL169 and FDL176 in Healthy Subjects
• Official Title: A Phase 1, Open Label, Drug-Drug Interaction Study of FDL169 and FDL176 in Healthy Subjects
• Brief Summary: This is an 2-part study. 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 FDL176 with and without co-administration of FDL169 .
• Detailed Description: This is an open-label, non-randomised, single-sequence 2-part study. Enrolment into Part 2 of the study will begin after Part 1 is complete, and a review of safety and pharmacokinetic data has been completed.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 FDL176 once daily (QD) with and without co-administration of FDL169.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

Drug: FDL176 & FDL169 coadministration

CFTR corrector and potentiator

Study Arms

• Experimental: Part 1:FDL176 & FDL169 coadministration
  To receive a single dose of FDL176 on Day 1, followed up FDL169 TID starting Day 8; and another single dose of FDL176 on Day 22.
  Intervention: Drug: FDL176 & FDL169 coadministration
• Experimental: Part 2:FDL176 & FDL169 coadministration
  To receive FDL176 QD starting Day 1, and FDL169 TID starting Day 8
  Intervention: Drug: FDL176 & FDL169 coadministration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2018): 16
• Original Estimated Enrollment (submitted: April 24, 2018): 32
• Actual Study Completion Date: August 22, 2018
• Actual Primary Completion Date: August 22, 2018 (Final data collection date for primary outcome measure)

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, unless in the opinion of the Investigator (or delegate) .
• 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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03516331
• Other Study ID Numbers: FDL169-2017-07
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Flatley Discovery Lab LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Flatley Discovery Lab LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Claudia Ordonez, MD; Flatley Discovery Lab

• PRS Account: Flatley Discovery Lab LLC
• Verification Date: November 2018