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

A Phase 1, Open Label, Drug-Drug Interaction Study of FDL169 and FDL176 in Healthy Subjects

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 .

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: FDL176 & FDL169 coadministration

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
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Ruddington
    • Nottingham, Ruddington, United Kingdom, NG11 6JS
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: FDL176 & FDL169 coadministration; CFTR corrector and potentiator
Experimental: Part 2:FDL176 & FDL169 coadministration; To receive FDL176 QD starting Day 1, and FDL169 TID starting Day 8	Drug: FDL176 & FDL169 coadministration; CFTR corrector and potentiator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters, Cmax	The pharmacokinetic parameters of FDL176 when co-administered with FDL169, compared to the pharmacokinetics of FDL176 alone; maximal plasma concentration (Cmax)	72 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	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.	72 days

Collaborators and Investigators

• Sponsor: Flatley Discovery Lab LLC
• Investigators: Study Chair: Claudia Ordonez, MD, Flatley Discovery Lab

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2018
• Primary Completion (Actual): August 22, 2018
• Study Completion (Actual): August 22, 2018

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (Actual): May 4, 2018

Study Record Updates

• Last Update Posted (Actual): November 2, 2018
• Last Update Submitted That Met QC Criteria: November 1, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cystic Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: FDL169-2017-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No