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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03173573




Registration number
NCT03173573
Ethics application status
Date submitted
30/05/2017
Date registered
2/06/2017
Date last updated
6/09/2018

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability and PK Profile of FDL176 in Healthy and CF Participants
Scientific title
A Five Part Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetic (PK) Profile of Single and Repeat Oral Doses of FDL176 in Healthy and Cystic Fibrosis (CF) Participants
Secondary ID [1] 0 0
FDL176-2016-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FDL176
Treatment: Drugs - Placebo

Experimental: Part 1 SAD FDL176 level 1 to 6 - Part 1: Single dose of FDL176 test formulation Level 1 to 6 on healthy males.

Placebo Comparator: Part 1 SAD Placebo - Part 1: Single dose of Placebo for FDL176.

Experimental: Part 2 SAD FDL176 at fasted state - Part 2: single dose of FDL176 test formulation, fasted state.

Experimental: Part 2 SAD FDL176 at fed state - Part 2: single dose of FDL176 test formulation, fed state

Experimental: Part 3 SAD FDL176 test formulation - Part 3: Single dose of FDL176 test formulation on healthy females.

Placebo Comparator: Part 3 SAD placebo - Part 3: Single dose of Placebo for FDL176.

Experimental: Part 4 MAD FDL176 Level 1 to 3 - Part 4: Dose escalation of FDL176 test formulation Level 1 to 3.

Placebo Comparator: Part 4 MAD Placebo - Part 4: Dose escalation of Placebo for FDL176 Level 1 to 3.

Experimental: Part 5 SAD FDL176 test formulation - Part 5: Single dose of FDL176 test formulation.


Treatment: Drugs: FDL176
CFTR modulator

Treatment: Drugs: Placebo
Placebo for FDL176
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1 and Part 4: Incidence of Treatment-Emergent Adverse Events.
Timepoint [1] 0 0
Part 1: 4 weeks; Part 4: 6 weeks
Primary outcome [2] 0 0
Part 2, 3 and 5: Pharmacokinetic parameters, Cmax
Timepoint [2] 0 0
Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks
Primary outcome [3] 0 0
Part 2, 3 and 5: Pharmacokinetic parameters, Tmax
Timepoint [3] 0 0
Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks
Primary outcome [4] 0 0
Part 2, 3 and 5: Pharmacokinetic parameters, AUC
Timepoint [4] 0 0
Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks
Primary outcome [5] 0 0
Part 2, 3 and 5: Pharmacokinetic parameters, CL/F
Timepoint [5] 0 0
Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks
Primary outcome [6] 0 0
Part 2, 3 and 5: Pharmacokinetic parameters, V/F
Timepoint [6] 0 0
Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks
Secondary outcome [1] 0 0
Part 2, 3, and 5: Incidence of Treatment-Emergent Adverse Events.
Timepoint [1] 0 0
Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks
Secondary outcome [2] 0 0
Part 1 and 4: Pharmacokinetic parameters, Cmax
Timepoint [2] 0 0
Part 1: 4 weeks; Part 4: 6 weeks
Secondary outcome [3] 0 0
Part 1 and 4: Pharmacokinetic parameters,Tmax
Timepoint [3] 0 0
Part 1: 4 weeks; Part 4: 6 weeks
Secondary outcome [4] 0 0
Part 1 and 4: Pharmacokinetic parameters,AUC
Timepoint [4] 0 0
Part 1: 4 weeks; Part 4: 6 weeks
Secondary outcome [5] 0 0
Part 1 and 4: Pharmacokinetic parameters, CL/F
Timepoint [5] 0 0
Part 1: 4 weeks; Part 4: 6 weeks
Secondary outcome [6] 0 0
Part 1 and 4: Pharmacokinetic parameters, V/F
Timepoint [6] 0 0
Part 1: 4 weeks; Part 4: 6 weeks

Eligibility
Key inclusion criteria
Inclusion Criteria (Part 1 to Part 4):

- If sexually active, must be willing to use two highly effective methods of birth
control from Day 1 until 3 months after the last dose of investigational medicinal
product (IMP)

- Body mass index (BMI) between 19 and 30 kg/m2 inclusive.

- Healthy as determined by the PI or delegate, based upon a medical evaluation including
medical history, physical examination, laboratory tests and ECG.

Inclusion Criteria (Part 5):

- Males and females aged 18 years and older.

- Diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative
pilocarpine iontophoresis or two CF-causing mutations, documented in the participant's
medical record.

- History of pancreatic insufficiency, documented in the participant's medical record.

- Stable CF disease as judged by the Investigator (or delegate).

- Forced expiratory volume in one second (FEV1) >40% of predicted normal for age, sex
and height at screening.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria (Part 1 to 4):

- 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 PK of the participant or would place the participant at
increased risk.

- Surgery within the past three months prior to the first study drug administration
determined by the PI or delegate to be clinically relevant.

- Alkaline phosphatase (ALP), aspartate aminotransferase (AST) and/or alanine
aminotransferase (ALT) >1.5 x upper limit of normal (ULN) at screening. Repeat testing
at screening is acceptable for out of range values following approval by the Sponsor's
Medical Monitor.

- 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 creatinine clearance <60 mL/min using
the Modification of Diet in Renal Disease (MDRD) equation

- History of prolonged QT and/or QTcF interval.

- ECG with a single QTcF >450 msec in males, >460 msec in females, at Screening.

- Positive urinary drugs of abuse screen at Screening or Day -1, or positive alcohol
screen at Screening or Day -1

- History of human immunodeficiency virus (HIV) or positive HIV, hepatitis B or
hepatitis C results at screening.

- 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)
and the Sponsor's Medical Monitor the medication will not interfere with the study
procedures or compromise participant safety. Hormonal contraceptives are allowed.

- 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,
unless in the opinion of the Investigator (or delegate) and the Sponsor's Medical
Monitor the medication will not interfere with the study procedures or compromise
participant safety.

- Pregnant or nursing females. Female participants of childbearing potential must have a
negative pregnancy test at the screening visit. Determination of participant
eligibility will be at the discretion of the Investigator (or delegate) following
consultation with the Sponsor's Medical Monitor.

- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a
half-pint (~240 mL) of beer, one glass (125 mL) of wine, or one (25 mL) measure of
spirits.

- Current smoking or use of tobacco products or substitutes. Former smokers will be
eligible, provided they have not smoked for at least 6 months before Day 1.

- Participation in another clinical trial involving receipt of an IMP within the past 90
days or exposure to more than four new chemical entities with 12 months of the first
dosing day.

Exclusion Criteria (Part 5):

- A pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks
prior to the Baseline (Day 1) visit.

- Abnormal liver function =3 × ULN: AST, ALT, total bilirubin.

- 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 creatinine clearance <60 mL/min using
the MDRD equation.

- Hemoglobin <10 g/dL.

- History of prolonged QT and/or QTcF interval.

- ECG with a single QTcF >450 msec in males, >460 msec in females, at Screening.

- Use of ivacaftor or lumacaftor within 14 days prior to Day 1.

- Any change (initiation, change in type of drug, dose modification, schedule
modification, interruption, discontinuation, or re-initiation) in a chronic
treatment/prophylaxis regimen for CF or CF related conditions within 4 weeks prior to
Day 1.

- Pregnant or nursing females. Female participants of childbearing potential must have a
negative pregnancy test at the screening visit. Determination of participant
eligibility will be at the discretion of the Investigator (or delegate) following
consultation with the Sponsor's Medical Monitor.

- Participation in another clinical trial involving receipt of an IP within the past 90
days or exposure to more than four new chemical entities with 12 months of the first
dosing day.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/05/2018
Sample size
Target
Accrual to date
Final
109
Recruitment in Australia
Recruitment state(s)
QueenlandQLD,WA
Recruitment hospital [1] 0 0
Wayne Hooper Clinic Clive Berghofer Cancer research Center - Herston
Recruitment hospital [2] 0 0
Mater Hospital - South Brisbane
Recruitment hospital [3] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
4006 - Herston
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6009 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Flatley Discovery Lab LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a 5-part study of FDL176. Part 1 is a double blind, placebo-controlled, dose
escalation study in healthy male participants. Part 2 is a single dose, open-label study in
healthy male participants. Part 3 is a single dose, double blind, placebo-controlled study in
healthy female participants. Part 4 is a randomised, double-blind, placebo-controlled,
dose-escalation study in healthy male and female participants.Part 5 is a single dose,
open-label study in male and female participants with CF.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03173573
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Claudia Ordonez, MD
Address 0 0
Flatley Discovery Lab
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03173573