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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03173573
Recruitment Status : Completed
First Posted : June 2, 2017
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
Flatley Discovery Lab LLC

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: FDL176 Drug: Placebo Phase 1

Detailed Description:
This is a 5-part study. Part 1 is a double blind, placebo-controlled, dose escalation, first-in-human study to assess the safety, tolerability and PK profiles following single oral administration of FDL176 to healthy male participants. Part 2 is a single dose, open-label study in healthy male participants to determine the effect of food on the PK profile of FDL176. Part 3 is a single dose, double blind, placebo-controlled study in healthy female participants to assess the PK, safety and tolerability profiles of FDL176. Part 4 is a randomised, double-blind, placebo-controlled, dose-escalation study to assess the safety, tolerability and PK profiles following multiple oral administrations of FDL176 to healthy male and female participants. Part 5 is a single dose, open-label study in male and female participants with CF to determine the PK profile of FDL176.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 5-part study. Part 1,3,4: parallel assignment; Part 2: cross over assignment; Part 5: single assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Part 1,3,4: Double blind; Part 2, 5: open label.
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 27, 2017
Actual Primary Completion Date : May 31, 2018
Actual Study Completion Date : May 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Part 1 SAD FDL176 level 1 to 6
Part 1: Single dose of FDL176 test formulation Level 1 to 6 on healthy males.
Drug: FDL176
CFTR modulator

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

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

Experimental: Part 2 SAD FDL176 at fed state
Part 2: single dose of FDL176 test formulation, fed state
Drug: FDL176
CFTR modulator

Experimental: Part 3 SAD FDL176 test formulation
Part 3: Single dose of FDL176 test formulation on healthy females.
Drug: FDL176
CFTR modulator

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

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

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

Experimental: Part 5 SAD FDL176 test formulation
Part 5: Single dose of FDL176 test formulation.
Drug: FDL176
CFTR modulator




Primary Outcome Measures :
  1. Part 1 and Part 4: Incidence of Treatment-Emergent Adverse Events. [ Time Frame: Part 1: 4 weeks; Part 4: 6 weeks ]
    Part 1 and Part 4: Safety and tolerability of FDL176 in healthy male participants as determined by the incidence of adverse events (AE)s and serious adverse events(SAE)s.

  2. Part 2, 3 and 5: Pharmacokinetic parameters, Cmax [ Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks ]
    The pharmacokinetic parameters of FDL176: maximal plasma concentration

  3. Part 2, 3 and 5: Pharmacokinetic parameters, Tmax [ Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks ]
    The pharmacokinetic parameters of FDL176: maximal concentration

  4. Part 2, 3 and 5: Pharmacokinetic parameters, AUC [ Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks ]
    The pharmacokinetic parameters of FDL176: area under the plasma concentration curve

  5. Part 2, 3 and 5: Pharmacokinetic parameters, CL/F [ Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks ]
    The pharmacokinetic parameters of FDL176: clearance

  6. Part 2, 3 and 5: Pharmacokinetic parameters, V/F [ Time Frame: Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks ]
    The pharmacokinetic parameters of FDL176: apparent volume of distribution


Secondary Outcome Measures :
  1. 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 ]
    Safety and tolerability of FDL176 in healthy male participants as determined by the incidence of adverse events (AE)s and serious adverse events(SAE)s.

  2. Part 1 and 4: Pharmacokinetic parameters, Cmax [ Time Frame: Part 1: 4 weeks; Part 4: 6 weeks ]
    The pharmacokinetic parameters of FDL176: maximal plasma concentration

  3. Part 1 and 4: Pharmacokinetic parameters,Tmax [ Time Frame: Part 1: 4 weeks; Part 4: 6 weeks ]
    The pharmacokinetic parameters of FDL176: maximal concentration

  4. Part 1 and 4: Pharmacokinetic parameters,AUC [ Time Frame: Part 1: 4 weeks; Part 4: 6 weeks ]
    The pharmacokinetic parameters of FDL176: area under the plasma concentration curve

  5. Part 1 and 4: Pharmacokinetic parameters, CL/F [ Time Frame: Part 1: 4 weeks; Part 4: 6 weeks ]
    The pharmacokinetic parameters of FDL176: clearance

  6. Part 1 and 4: Pharmacokinetic parameters, V/F [ Time Frame: Part 1: 4 weeks; Part 4: 6 weeks ]
    The pharmacokinetic parameters of FDL176: apparent volume of distribution



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03173573


Locations
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Australia, Queenland
Wayne Hooper Clinic Clive Berghofer Cancer research Center
Herston, Queenland, Australia, 4006
Australia, Queensland
Mater Hospital
South Brisbane, Queensland, Australia, 4101
Australia, Western Australia
Linear Clinical Research
Perth, Western Australia, Australia, 6009
Sponsors and Collaborators
Flatley Discovery Lab LLC
Investigators
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Study Chair: Claudia Ordonez, MD Flatley Discovery Lab

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Responsible Party: Flatley Discovery Lab LLC
ClinicalTrials.gov Identifier: NCT03173573     History of Changes
Other Study ID Numbers: FDL176-2016-01
First Posted: June 2, 2017    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Flatley Discovery Lab LLC:
Cystic Fibrosis

Additional relevant MeSH terms:
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Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases