ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of RPL554 in Patients With Cystic Fibrosis

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02919995
Recruitment Status : Recruiting
First Posted : September 30, 2016
Last Update Posted : August 1, 2017
Sponsor:
Collaborator:
Cystic Fibrosis Trust
Information provided by (Responsible Party):
Verona Pharma plc

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: RPL554 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : February 8, 2017
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Higher Dose RPL554
Single dose of inhaled 6 mg RPL554
Drug: RPL554
RPL554 suspension administered using a nebuliser

Experimental: Lower dose RPL554
Single dose of inhaled 1.5 mg RPL554
Drug: RPL554
RPL554 suspension administered using a nebuliser

Placebo Comparator: Placebo
Inhaled placebo dose
Drug: Placebo
Placebo solution administered using a nebuliser




Primary Outcome Measures :
  1. Exposure [ Time Frame: Over 24 hours after each treatment ]
    Area under the curve (AUC)

  2. Maximum plasma concentration [ Time Frame: Over 24 hours after each treatment ]
    Maximum concentration (Cmax)

  3. Time to maximum plasma concentration [ Time Frame: Over 24 hours after each treatment ]
    Time to maximum concentration (Tmax)

  4. Half life [ Time Frame: Over 24 hours after each treatment ]
    half life (t1/2)


Secondary Outcome Measures :
  1. Spirometry [ Time Frame: Over 24 hours after treatment ]
    Forced expired volume in one second (FEV1)

  2. Spirometry 2 [ Time Frame: Over 24 hours after treatment ]
    Forced vital capacity (FVC)

  3. Breath samples [ Time Frame: 8 and 24 hours after treatment ]
    Exhaled breath pH

  4. Laboratory safety tests 1 [ Time Frame: Screening and end of study ]
    Biochemistry

  5. Laboratory safety tests 2 [ Time Frame: Screening and end of study ]
    Haematology

  6. Laboratory safety tests 3 [ Time Frame: Screening and end of study ]
    Urinalysis

  7. Vital signs 1 [ Time Frame: Over 8 hours after treatment ]
    Pulse rate

  8. Vital signs 2 [ Time Frame: Over 8 hours after treatment ]
    Blood pressure

  9. ECG 1 [ Time Frame: Over 8 hours after treatment ]
    Heart rate

  10. ECG 2 [ Time Frame: Over 8 hours after treatment ]
    QT interval


Other Outcome Measures:
  1. Sputum rheology [ Time Frame: 8 and 12 hours after treatment ]
    Rheology

  2. Sputum measurements [ Time Frame: 8 and 12 hours after treatment ]
    Levels of inflammatory mediators



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. -

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): NCT02919995


Contacts
Contact: Andres Floto +44 (0)1223 768801

Locations
United Kingdom
Papworth Hospital Recruiting
Cambridge, United Kingdom, CB23 3RE
Contact: Andres Floto    +44 (0)1223768801      
Principal Investigator: Andres Floto         
Sponsors and Collaborators
Verona Pharma plc
Cystic Fibrosis Trust
Investigators
Principal Investigator: Andres Floto Cambridge Centre for Medical Research, Papworth Hospital

Responsible Party: Verona Pharma plc
ClinicalTrials.gov Identifier: NCT02919995     History of Changes
Other Study ID Numbers: RPL554-010-2015
2015-004263-36 ( EudraCT Number )
First Posted: September 30, 2016    Key Record Dates
Last Update Posted: August 1, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

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