A DDI Study of FDL169 and FDL176 in Healthy Subjects

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

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.

Study Overview

• Status: Suspended
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: FDL169; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 6AD
    • Celerion GB Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; To receive a single dose of FDL176 on Day 1, followed by FDL169 TID for 28 days starting on Day 29; and another single dose of FDL176 on Day 42.	Drug: FDL169; CFTR corrector; Drug: FDL176; CFTR potentiator
Experimental: Part 2; To receive FDL169 TID for 3 days from Day 1, followed by FDL176 QD for 19 days starting on Day 8; and FDL169 TID for 3 days from Day 24.	Drug: FDL169; CFTR corrector; Drug: FDL176; CFTR potentiator
Experimental: Part 3; FDL169 and FDL176 for 28 days and 4 weeks of follow-up	Drug: FDL169; CFTR corrector; Drug: FDL176; CFTR potentiator
Experimental: Part 4; FDL169 and FDL176 for 28 days and 4 weeks of follow-up	Drug: FDL169; CFTR corrector; Drug: FDL176; CFTR potentiator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters, Cmax	Part 1: the pharmacokinetic parameters of FDL176 when co-administered with FDL169, compared to the pharmacokinetics of FDL176 alone. Part 2: the pharmacokinetics of FDL169 when co-administered with FDL176, compared to the pharmacokinetics of FDL169 alone. Part 3: PK when co-administered. Part 4: Safety and tolerability with multiple dose co-administration in CF subjects	Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and tolerability when FDL176 and FDL169 are co-administrated,compared to FDL176 alone, and FDL169 alone, as determined by the incidence of adverse events (Aes) and serious adverse events (SAE)s. Part 4: Combination PK and CF transmembrane conductance regulator activity in CF subjects	Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks

Collaborators and Investigators

• Sponsor: Flatley Discovery Lab LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2018
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

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: FDL169-2018-10

Drug and device information, study documents

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