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A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of RV6153

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: NCT02517359
Recruitment Status : Terminated (Preset pharmacokinetic stopping criteria met at lower doses than expected.)
First Posted : August 7, 2015
Last Update Posted : March 4, 2016
Sponsor:
Information provided by (Responsible Party):
Respivert Ltd

Tracking Information
First Submitted Date  ICMJE July 28, 2015
First Posted Date  ICMJE August 7, 2015
Last Update Posted Date March 4, 2016
Study Start Date  ICMJE July 2015
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2015)
  • Safety and tolerability of single and repeat doses assessed by incidence of treatment emergent adverse events [ Time Frame: Up to 29 days post final dose ]
    Assessment of the number of adverse events reported by subjects following dosing
  • Safety and tolerability of single and repeat doses assessed by ECG (12-lead ECG) [ Time Frame: Up to 29 days post final dose ]
    12-lead ECGs will be obtained using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, and QTcB/QTcF intervals. ECGs will be measured after resting for 5 minutes
  • Safety and tolerability of single and repeat doses assessed by vital sign measurement (blood pressure & heart rate) [ Time Frame: Up to 29 days post final dose ]
    Blood pressure heart rate will be assessed together using an automated device after resting for 5 minutes. Blood pressure will include systolic and diastolic measurements.
  • Safety and tolerability of single and repeat doses assessed by respiration rate [ Time Frame: Up to 29 days post final dose ]
    Respiration rate will be measured after resting for 5 minutes
  • Safety and tolerability of single and repeat doses assessed by temperature [ Time Frame: Up to 29 days post final dose ]
    Temperature will be measured orally
  • Safety and tolerability of single and repeat doses assessed by spirometry [ Time Frame: Up to 29 days post final dose ]
    Pulmonary function test measured from forced expiratory volume in 1 second (FEV1). Pulmonary function test will be repeated until three technically acceptable measurements have been made.
  • Safety and tolerability of single and repeat doses by assessment of clinical laboratory tests [ Time Frame: Up to 29 days post final dose ]
    Clinical laboratory tests include haematology, clinical chemistry, urinalysis and additional parameters
  • Pharmacodynamic (PD) effect of repeat doses of RV6153 assessed by sputum cell biomarkers [ Time Frame: Cohort 13 (subjects who smoke) only - assessments at screening and Days 1, 7 & 14 ]
    Sputum samples will be collected to evaluate PD effects of repeat doses of RV6153 by assessment of phosphatidylinositol biphosphate (PIP2) and phosphatidylinositol triphosphate (PIP3).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2015)
Plasma RV6153 levels [ Time Frame: Cohorts 1-9: Day 1, 10 samples, Days 2,8,15&29, 1 sample per day; Cohorts 10, 12 & 13: Days 1,7&14, 10 samples per day, Days 2,8-13,1,21,28&42, 1 sample per day; Cohort 11: Days 1,14&28, 10 samples per day, Days 7,21,26,27,29,35,42&56, 1 sample per day ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 4, 2015)
Sputum markers of inflammation [ Time Frame: Cohort 13 (subjects who smoke) only - assessments at screening and Days 1, 7 & 14 ]
Sputum samples will be collected to evaluate effects on inflammation by assessment of myeloperoxidase, IL-6, IL-8, TNF alpha and other exploratory parameters
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of RV6153
Official Title  ICMJE A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Treatment With Single and Repeat Doses of Inhaled RV6153 in Healthy Subjects and Subjects With Stable Asthma.
Brief Summary

RV6153 is a new medicine being developed for possible treatment of asthma and smoking related lung disease (also known as chronic obstructive pulmonary disease - COPD).

The main purpose of this study is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of RV6153

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Asthma
  • Healthy Volunteers
Intervention  ICMJE
  • Drug: RV6153 single dose
    Safety and tolerability of single doses
  • Drug: RV6153 matching placebo single dose
    Safety and tolerability of single doses
  • Drug: RV6153 14 day repeat dose
    Safety and tolerability of repeat doses
  • Drug: RV6153 matching placebo 14 day repeat dose
    Safety and tolerability of repeat doses
  • Drug: RV6153 28 day repeat dose
    Safety and tolerability of repeat doses
  • Drug: RV6153 matching placebo 28 day repeat dose
    Safety and tolerability of repeat doses
Study Arms  ICMJE
  • Experimental: Single dose, healthy volunteers
    Interventions:
    • Drug: RV6153 single dose
    • Drug: RV6153 matching placebo single dose
  • Experimental: 14 day repeat dose, healthy volunteers
    Interventions:
    • Drug: RV6153 14 day repeat dose
    • Drug: RV6153 matching placebo 14 day repeat dose
  • Experimental: 28 day repeat dose, healthy volunteers
    Interventions:
    • Drug: RV6153 28 day repeat dose
    • Drug: RV6153 matching placebo 28 day repeat dose
  • Experimental: 14 day repeat dose, asthma patients
    Interventions:
    • Drug: RV6153 14 day repeat dose
    • Drug: RV6153 matching placebo 14 day repeat dose
  • Experimental: 14 day repeat dose, smokers
    Interventions:
    • Drug: RV6153 14 day repeat dose
    • Drug: RV6153 matching placebo 14 day repeat dose
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 Terminated
Actual Enrollment  ICMJE
 (submitted: January 13, 2016)
55
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2015)
119
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Cohorts 1 to 13 (all subjects)

  • Subject must be a man or woman aged between 18 to 65 years of age, inclusive: Women of non-childbearing potential only - defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile or permanently sterilised. Men who are willing and able to use suitable contraception methods listed in Section 4.5.1, from the time of the first dose of study medication until 90 days after discharge from the study.
  • A woman must have a negative serum β human chorionic gonadotropin (β-hCG) test at screening and a negative urine pregnancy test at Day -1.
  • Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
  • Each subject must sign an informed consent form (ICF)
  • Body weight ≥50 kg and BMI within the range 19-29 kg/m2 (inclusive).
  • Average QTcF <450 msec at screening and Day -1 visits
  • Vital sign assessments within normal ranges.

Cohorts 1 to 11 and 13 (healthy volunteers and smokers only)

  • Healthy as determined by a physician, based on a full medical evaluation including medical history, physical examination, laboratory tests.
  • Spirometry readings (FEV1 and FVC) to be ≥80% predicted value and FEV1/FVC ratio >0.7 at screening.

Cohort 12 (asthma patients only)

  • Documented history of asthma, first diagnosed at least 6 months prior to the screening visit.
  • Currently being treated with daily standard of care asthma therapy
  • Have a diagnosis of asthma confirmed at screening by bronchodilator reversibility.
  • Have stable asthma based on physician assessment at screening and prior to randomisation, with no asthma exacerbation requiring augmentation of therapy in the 12 weeks prior to screening and no hospitalization or visit to accident and emergency for asthma in the 12 months prior to screening.
  • Have a pre-bronchodilator forced expiratory volume in the first second (FEV1) ≥60% and ≤85% of predicted normal value at screening.
  • Subject must be otherwise healthy on the basis of full medical evaluation performed at screening.

Cohort 13 (smokers only)

  • Subjects who are current daily cigarette smokers.

Exclusion Criteria:

Cohorts 1 to 13 (all subjects)

  • Upper or lower respiratory tract infection within 4 weeks of the screening visit and prior to randomisation.
  • A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody result at screening.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
  • Positive test for alcohol or drugs of abuse.
  • Use of prescription medications within 14 days prior to the screening visit and agree not to use prescription medications throughout the duration of the study.
  • Are taking over the counter (OTC) medications for 14 days prior to Screening visit and agree to refrain from taking such medications throughout the study.
  • History of regular alcohol consumption within 6 months of the study
  • Definite or suspected history of drug or alcohol abuse within the previous 5 years.
  • A positive test for HIV antibody.
  • Received an experimental drug or used an experimental medical device within 3 months or within a period less than five times the drug's half-life before the first dose of the study drug is scheduled.
  • Allergy to any of the active or inactive ingredients (including lactose and milk protein intolerance) in the study medication.
  • History of drug, or other allergy that would contraindicate their participation.
  • A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
  • Donated blood or blood products or had substantial loss of blood (more than 500 mL) within 3 months before the first administration of study drug or intention to donate blood or blood products during the study.
  • Subject is mentally or legally incapacitated.
  • Subject is an employee of the Sponsor or contract research organization (CRO), or a relative of an employee of the Sponsor or CRO.
  • Unable or unwilling to undergo multiple venipuncture procedures or the subject has poor access to veins suitable for cannulation.
  • Any other reason that the Investigator considers makes the subject unsuitable to participate.

Cohorts 1 to 11 (healthy subjects only)

  • Any acute or chronic illness or clinically relevant abnormality identified on the screening medical assessment.
  • The subject is a smoker or has smoked or used nicotine-containing products (including e-cigarettes or other nicotine containing products) within the 6 months prior to screening or has a smoking history of ≥5 pack years.
  • Positive urine cotinine test at the screening visit indicative of smoking or use of tobacco or nicotine-containing products.

Cohort 12 (asthma patients only)

  • Has ever had an episode of life-threatening asthma defined as respiratory arrest, intubation for asthma, or ICU admission for asthma
  • Has been hospitalized for greater than 24 hours due to asthma in the 5 years prior to the study.
  • Has experienced an asthma exacerbation in the 3 months prior to screening (and prior to randomisation) requiring management with systemic or injectable steroids.
  • Has uncontrolled (severe) asthma and/or use of the study prohibited asthma medications.
  • The subject is a smoker (regular or irregular), or has smoked or used nicotine-containing products (including e-cigarettes) within the 6 months prior to screening (or a smoking history ≥10 pack years).
  • Positive urine cotinine test at the screening visit, and at Day -1, indicative of smoking or use of tobacco or nicotine-containing products.

Cohort 13 (smokers only)

  • Any acute or chronic illness, including a diagnosis of COPD, or clinically relevant abnormality identified on the screening medical assessment.
  • Subjects who are unable to produce a viable sputum sample at screening
  • Subjects whose primary consumption of tobacco is via methods other than cigarettes. Primary methods of tobacco consumption that are excluded include, but are not limited to pipes, cigars and e-cigarettes.
  • Urinary cotinine levels at screening <30 nanograms (ng)/mL.
  • Subjects who have asthma or a history of asthma (except in childhood and which has now remitted).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
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 NCT02517359
Other Study ID Numbers  ICMJE SFT001
2015-000440-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Respivert Ltd
Study Sponsor  ICMJE Respivert Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christopher O'Brien, MD, PhD, FCCP Sponsor GmbH
PRS Account Respivert Ltd
Verification Date March 2016

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