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A Study of RPL554 in Patients With Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT02919995
Recruitment Status : Completed
First Posted : September 30, 2016
Results First Posted : March 20, 2019
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
Cystic Fibrosis Trust
Information provided by (Responsible Party):
Verona Pharma plc

Tracking Information
First Submitted Date  ICMJE September 21, 2016
First Posted Date  ICMJE September 30, 2016
Results First Submitted Date  ICMJE December 7, 2018
Results First Posted Date  ICMJE March 20, 2019
Last Update Posted Date May 14, 2019
Actual Study Start Date  ICMJE February 8, 2017
Actual Primary Completion Date November 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • AUC by Dose [ Time Frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose after each treatment ]
    Area under the curve (AUC)
  • Maximum Plasma Concentration After Each Dose [ Time Frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose ]
    Maximum plasma concentration (Cmax) after a single dose of RPL554
  • Time to Maximum Plasma Concentration After Each Dose [ Time Frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose ]
    Time to maximum concentration (Tmax) after a single dose of RPL554
  • Half Life for Each Dose [ Time Frame: Pre dose, 15 and 30 minutes and 1, 2, 4, 6, 8 and 24 hours post dose ]
    Half life (t1/2) of RPL554
Original Primary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
  • Exposure [ Time Frame: Over 24 hours after each treatment ]
    Area under the curve (AUC)
  • Maximum Plasma Concentration [ Time Frame: Over 24 hours after each treatment ]
    Maximum concentration (Cmax)
  • Time to Maximum Plasma Concentration [ Time Frame: Over 24 hours after each treatment ]
    Time to maximum concentration (Tmax)
  • Half Life [ Time Frame: Over 24 hours after each treatment ]
    half life (t1/2)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Peak FEV1 for Each Treatment [ Time Frame: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose after treatment ]
    Maximum Forced expired volume in one second (FEV1) measured using spirometry
  • AUC FEV1(0-4h) [ Time Frame: Pre dose and 15 and 30 minutes and 1, 2 and 4 hours post dose ]
    Area under the curve for FEV1 over 4 hours measured using spirometry
  • AUC FEV1(0-6h) [ Time Frame: Pre dose and 15 and 30 minutes and 1, 2, 4 and 6 hours post dose ]
    Area under the curve FEV1 over 6 hours measured using spirometry
  • AUC FEV1(0-8h) [ Time Frame: pre dose and 15 and 30 minutes and 1, 2, 4, 6 and 8 hours post dose ]
    Area under the curve for FEV1 over 8 hours measured using spirometry
  • FVC [ Time Frame: Over 24 hours after treatment ]
    Forced vital capacity (FVC) measured using spirometry
  • Breath Samples [ Time Frame: 8 and 24 hours after treatment ]
    Exhaled breath pH
  • Laboratory Safety Tests 1 [ Time Frame: Screening and end of study ]
    Biochemistry panel parameters
  • Laboratory Safety Tests 2 [ Time Frame: Screening and end of study ]
    Haematology panel parameters
  • Laboratory Safety Tests 3 [ Time Frame: Screening and end of study ]
    Urinalysis measured by urine dipstick
  • Vital Signs 1 [ Time Frame: Over 8 hours after treatment ]
    Pulse rate after 5 minutes supine
  • Vital Signs 2 [ Time Frame: Over 8 hours after treatment ]
    Blood pressure after 5 minutes supine
  • ECG 1 [ Time Frame: Over 8 hours after treatment ]
    Heart rate
  • ECG 2 [ Time Frame: Over 8 hours after treatment ]
    QT interval
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
  • Spirometry [ Time Frame: Over 24 hours after treatment ]
    Forced expired volume in one second (FEV1)
  • Spirometry 2 [ Time Frame: Over 24 hours after treatment ]
    Forced vital capacity (FVC)
  • Breath Samples [ Time Frame: 8 and 24 hours after treatment ]
    Exhaled breath pH
  • Laboratory Safety Tests 1 [ Time Frame: Screening and end of study ]
    Biochemistry
  • Laboratory Safety Tests 2 [ Time Frame: Screening and end of study ]
    Haematology
  • Laboratory Safety Tests 3 [ Time Frame: Screening and end of study ]
    Urinalysis
  • Vital Signs 1 [ Time Frame: Over 8 hours after treatment ]
    Pulse rate
  • Vital Signs 2 [ Time Frame: Over 8 hours after treatment ]
    Blood pressure
  • ECG 1 [ Time Frame: Over 8 hours after treatment ]
    Heart rate
  • ECG 2 [ Time Frame: Over 8 hours after treatment ]
    QT interval
Current Other Pre-specified Outcome Measures
 (submitted: December 7, 2018)
  • Sputum Rheology [ Time Frame: 8 and 12 hours after treatment ]
    Rheological analysis for interleukin 8, tumour necrosis factor alpha and myeloperoxidase
  • Sputum Measurements [ Time Frame: 8 and 12 hours after treatment ]
    Levels of inflammatory mediators
Original Other Pre-specified Outcome Measures
 (submitted: September 27, 2016)
  • Sputum Rheology [ Time Frame: 8 and 12 hours after treatment ]
    Rheology
  • Sputum Measurements [ Time Frame: 8 and 12 hours after treatment ]
    Levels of inflammatory mediators
 
Descriptive Information
Brief Title  ICMJE A Study of RPL554 in Patients With Cystic Fibrosis
Official Title  ICMJE A Phase IIa, Randomised, Double Blind, Placebo Controlled, Three Way Crossover Study to Assess the Pharmacokinetics of RPL554 Administered to Adult Patients With Cystic Fibrosis.
Brief Summary This study evaluates two doses of RPL554 and placebo in adult patients with cystic fibrosis. All patients receive all three treatments in a randomised sequence.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: RPL554
    RPL554 suspension administered using a nebuliser
  • Drug: Placebo
    Placebo solution administered using a nebuliser
Study Arms  ICMJE
  • Experimental: Higher Dose RPL554
    Single dose of inhaled 6 mg RPL554
    Intervention: Drug: RPL554
  • Experimental: Lower dose RPL554
    Single dose of inhaled 1.5 mg RPL554
    Intervention: Drug: RPL554
  • Placebo Comparator: Placebo
    Inhaled placebo dose
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2016)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 3, 2017
Actual Primary Completion Date November 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.

    2. Male or female aged ≥18 years at the time of informed consent. Females of childbearing potential must have been using a consistent and reliable form of contraception (see Appendix 1) from the last menses before the first study treatment administration, and must commit to continue to do so during the study and for 3 months after the last dose of study treatment.

    3. Have a 12-lead ECG recording at screening (Visit 1) and Visit 2 pre-dose showing the following:

    • Heart rate between 45 and 90 beats per minute
    • QT interval corrected for heart rate using Fridericia's formula (QTcF) interval ≤450 msec
    • QRS interval ≤120 msec
    • PR interval ≤220 msec
    • No clinically significant abnormality including morphology (e.g. left bundle branch block, atrioventricular nodal dysfunction, ST segment abnormalities) 4. Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.

      5. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) with a minimum weight of 40 kg.

      6. Patients with a genetic diagnosis of CF. 7. Spirometry at screening demonstrating an FEV1 ≥40% and ≤80% of predicted normal.

      8. Capable of withdrawing from long acting bronchodilators1 until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study treatment.

      9. Clinically stable CF in the 2 weeks prior to randomisation (Visit 2).

Exclusion Criteria:

  1. History of cirrhotic liver disease or portal hypertension.
  2. CF exacerbation requiring hospitalisation in the month prior to screening (Visit 1) or prior to randomisation (Visit 2).
  3. Use of oral or intravenous antibiotics (in additional to usual maintenance therapy) in the 2 weeks prior to screening (Visit 1) or randomisation (Visit 2).
  4. Other non-CF related respiratory disorders: Patients with a current diagnosis of active tuberculosis, lung cancer, sarcoidosis, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
  5. Previous lung resection or lung transplant.
  6. History of, or reason to believe a patient has, drug or alcohol abuse within the past 3 years.
  7. Received an experimental drug within 3 months or five half-lives, whichever is longer.
  8. Patients with a history of chronic uncontrolled disease including, but not limited to, cardiovascular (including arrhythmias), endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological or ophthalmic diseases that the Investigator believes are clinically significant.
  9. Documented cardiovascular disease: angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
  10. Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to screening (Visit 1) or will not have fully recovered from surgery, or planned surgery through the end of the study.
  11. Infection with nontuberculous mycobacteria, methicillin-resistant Staphylococcus aureus (MRSA), or Burkholderia species.
  12. Use of immune-suppression; long term use of prednisolone ≥10 mg/day.
  13. History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell).
  14. Clinically significant abnormal values for safety laboratory tests (haematology, biochemistry or urinalysis) at screening (Visit 1), as determined by the Investigator.
  15. A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
  16. Requires oxygen therapy, even on an occasional basis.
  17. Pregnancy or lactation (female subjects only).
  18. Any other reason that the Investigator considers makes the patient unsuitable to participate. -
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02919995
Other Study ID Numbers  ICMJE RPL554-010-2015
2015-004263-36 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Verona Pharma plc
Study Sponsor  ICMJE Verona Pharma plc
Collaborators  ICMJE Cystic Fibrosis Trust
Investigators  ICMJE
Principal Investigator: Andres Floto Cambridge Centre for Medical Research, Papworth Hospital
PRS Account Verona Pharma plc
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP