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

NCT03173573 | Completed Phase 1 DMC

• 1 other identifier: FDL176-2016-01
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 3

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis

Outcome Measures

Primary Outcomes (6)

• Part 1 and Part 4: Incidence of Treatment-Emergent Adverse Events.

  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.

  Part 1: 4 weeks; Part 4: 6 weeks

• Part 2, 3 and 5: Pharmacokinetic parameters, Cmax

  The pharmacokinetic parameters of FDL176: maximal plasma concentration

  Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks

• Part 2, 3 and 5: Pharmacokinetic parameters, Tmax

  The pharmacokinetic parameters of FDL176: maximal concentration

  Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks

• Part 2, 3 and 5: Pharmacokinetic parameters, AUC

  The pharmacokinetic parameters of FDL176: area under the plasma concentration curve

  Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks

• Part 2, 3 and 5: Pharmacokinetic parameters, CL/F

  The pharmacokinetic parameters of FDL176: clearance

  Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks

• Part 2, 3 and 5: Pharmacokinetic parameters, V/F

  The pharmacokinetic parameters of FDL176: apparent volume of distribution

  Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks

Secondary Outcomes (6)

• Part 2, 3, and 5: Incidence of Treatment-Emergent Adverse Events.

  Part 2: 5 weeks, Part 3: 4 weeks and Part 5: 4 weeks

• Part 1 and 4: Pharmacokinetic parameters, Cmax

  Part 1: 4 weeks; Part 4: 6 weeks

• Part 1 and 4: Pharmacokinetic parameters,Tmax

  Part 1: 4 weeks; Part 4: 6 weeks

• Part 1 and 4: Pharmacokinetic parameters,AUC

  Part 1: 4 weeks; Part 4: 6 weeks

• Part 1 and 4: Pharmacokinetic parameters, CL/F

  Part 1: 4 weeks; Part 4: 6 weeks

Study Arms (9)

Part 1 SAD FDL176 level 1 to 6

EXPERIMENTAL

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

Drug: FDL176

Part 1 SAD Placebo

PLACEBO COMPARATOR

Part 1: Single dose of Placebo for FDL176.

Drug: Placebo

Part 2 SAD FDL176 at fasted state

EXPERIMENTAL

Part 2: single dose of FDL176 test formulation, fasted state.

Drug: FDL176

Part 2 SAD FDL176 at fed state

EXPERIMENTAL

Part 2: single dose of FDL176 test formulation, fed state

Drug: FDL176

Part 3 SAD FDL176 test formulation

EXPERIMENTAL

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

Drug: FDL176

Part 3 SAD placebo

PLACEBO COMPARATOR

Part 3: Single dose of Placebo for FDL176.

Drug: Placebo

Part 4 MAD FDL176 Level 1 to 3

EXPERIMENTAL

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

Drug: FDL176

Part 4 MAD Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part 5 SAD FDL176 test formulation

EXPERIMENTAL

Part 5: Single dose of FDL176 test formulation.

Drug: FDL176

Interventions

FDL176 DRUG

CFTR modulator

Part 1 SAD FDL176 level 1 to 6; Part 2 SAD FDL176 at fasted state; Part 2 SAD FDL176 at fed state; Part 3 SAD FDL176 test formulation; Part 4 MAD FDL176 Level 1 to 3; Part 5 SAD FDL176 test formulation

Placebo DRUG

Placebo for FDL176

Part 1 SAD Placebo; Part 3 SAD placebo; Part 4 MAD Placebo

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

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 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.

Sponsors & Collaborators

• Flatley Discovery Lab LLC: lead

Study Sites (3)

Wayne Hooper Clinic Clive Berghofer Cancer research Center

Herston, Queenland, 4006, Australia

Location

Mater Hospital

South Brisbane, Queensland, 4101, Australia

Location

Linear Clinical Research

Perth, Western Australia, 6009, Australia

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 Officials

• Claudia Ordonez, MD

  Flatley Discovery Lab

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Part 1,3,4: Double blind; Part 2, 5: open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 5-part study. Part 1,3,4: parallel assignment; Part 2: cross over assignment; Part 5: single assignment

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 2, 2017
• Study Start: June 27, 2017
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: September 6, 2018

Record last verified: 2018-09

Locations

AU (3)