A DDI Study of FDL169 and FDL176 in Healthy Subjects

NCT03756922 | Suspended Phase 1 DMC

• 1 other identifier: FDL169-2018-10
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Part 1: 14 weeks; Part 2: 12 weeks; Part 3: 12weeks; Part 4: 12 weeks

Study Arms (4)

Part 1

EXPERIMENTAL

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; Drug: FDL176

Part 2

EXPERIMENTAL

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; Drug: FDL176

Part 3

EXPERIMENTAL

FDL169 and FDL176 for 28 days and 4 weeks of follow-up

Drug: FDL169; Drug: FDL176

Part 4

EXPERIMENTAL

FDL169 and FDL176 for 28 days and 4 weeks of follow-up

Drug: FDL169; Drug: FDL176

Interventions

FDL169 DRUG

CFTR corrector

Part 1; Part 2; Part 3; Part 4

FDL176 DRUG

CFTR potentiator

Part 1; Part 2; Part 3; Part 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Flatley Discovery Lab LLC: lead

Study Sites (1)

Celerion GB Ltd

Belfast, BT9 6AD, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Parts 1, 2, and 3 are Open Label, while Part 4 is randomized and blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel for Part 1 and Part 2; Sequential for Part 3 and Part 4

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Study Start: November 27, 2018
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: February 5, 2020

Record last verified: 2020-01

Locations

GB (1)