A Study to Assess the Safety, Tolerability and PK Profile of FDL176 in Healthy and CF Participants

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03173573
• Date of registration: 30/05/2017
• Prospective Registration: Yes
• Primary sponsor: Flatley Discovery Lab LLC
• 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
• Date of first enrolment: June 27, 2017
• Target sample size: 109
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03173573
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Claudia Ordonez, MD
• Affiliation: Flatley Discovery Lab

Key inclusion & exclusion 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.

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.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: FDL176

Drug: Placebo

Primary Outcome(s)

Part 2, 3 and 5: Pharmacokinetic parameters, AUC [Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks]

Part 1 and Part 4: Incidence of Treatment-Emergent Adverse Events. [Time Frame: Part 1: 4 weeks; Part 4: 6 weeks]

Part 2, 3 and 5: Pharmacokinetic parameters, V/F [Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks]

Part 2, 3 and 5: Pharmacokinetic parameters, CL/F [Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks]

Part 2, 3 and 5: Pharmacokinetic parameters, Cmax [Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks]

Part 2, 3 and 5: Pharmacokinetic parameters, Tmax [Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks]

Secondary Outcome(s)

Part 1 and 4: Pharmacokinetic parameters, Cmax [Time Frame: Part 1: 4 weeks; Part 4: 6 weeks]

Part 1 and 4: Pharmacokinetic parameters,Tmax [Time Frame: Part 1: 4 weeks; Part 4: 6 weeks]

Part 1 and 4: Pharmacokinetic parameters, CL/F [Time Frame: Part 1: 4 weeks; Part 4: 6 weeks]

Part 1 and 4: Pharmacokinetic parameters, V/F [Time Frame: Part 1: 4 weeks; Part 4: 6 weeks]

Part 1 and 4: Pharmacokinetic parameters,AUC [Time Frame: Part 1: 4 weeks; Part 4: 6 weeks]

Part 2, 3, and 5: Incidence of Treatment-Emergent Adverse Events. [Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks]

Secondary ID(s)

FDL176-2016-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors