Safety, Tolerability and Pharmacokinetic Study of Biota-CS-8958
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will look at the safety, tolerability and what the body does to CS-8958 given to
      40 healthy volunteers 18-55 years old. CS-8958 is a dry-powder investigational drug that is
      breathed into the lungs through an inhaler device. The researchers will collect information
      about any problems that volunteers have while taking the drug and about changes in blood
      pressure and how the heart is working. Volunteers will have breathing tests, physical
      examinations, and blood samples collected for laboratory tests. The researchers will also
      look at how much of the medication travels throughout the body versus how much stays only in
      the lungs. Doses of the medication will be tested at one level and then at higher and higher
      levels after a safety committee reviews the safety and tolerability information on volunteers
      prior to the next higher dose being given. Each volunteer will participate for up to 6 weeks
      from initial screening to the follow up visit and spend 7 days in the clinic.
    

Detailed description: 
      This study is a phase I, double-blind, placebo-controlled, ascending single inhaled dose,
      safety, tolerability and pharmacokinetic study of CS-8958 in healthy subjects. CS-8958 is an
      investigational drug substance, which is formulated as a dry-powder. Capsules of the dry
      powder are inserted into a FlowCaps® inhaler device. FlowCaps® is a re-fillable, dry-powder,
      breath-actuated inhaler device, which holds up to 14 capsules. Upon actuation the powder
      contained in one capsule is delivered to the respiratory tract. The primary study objective
      is to evaluate the safety and tolerability of CS-8958 (5, 10, 20, and 40 mg) in healthy
      subjects after a single dose administered via inhalation. Parameters are adverse events
      (AEs), vital signs including blood pressure/pulse rate (BP/PR) measurements, functional
      oxygen saturation of arterial haemoglobin (SpO2), electrocardiogram (ECG) examinations,
      spirometry (Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), FEV
      percentage in 1 second (FEV 1%), FEV1/FVC ratio, Forced Expiratory Flow Rate (FEF) 25%-75%,
      Peak Expiratory Flow Rate (PEFR), physical examinations, mood assessments, and laboratory
      parameters. The secondary study objective is to assess the systemic exposure of CS-8958 and
      its active metabolite R-125489 after single inhaled doses of CS-8958 in healthy subjects. At
      Covance Clinical Research Unit Ltd, Leeds, UK, 40 subjects will be studied in 4 groups
      (Groups A to D) with each group consisting of 10 subjects. Healthy male and female subjects
      aged 18-55 years inclusive will be recruited for the study. There will be four
      investigational product treatment groups (Groups A, B, C, and D). Within each group, subjects
      will be randomly allocated to Arm 1 or Arm 2. The study product doses will be administered in
      an escalating manner. The Safety Monitoring Committee (SMC) will review the safety and
      tolerability data from each group, prior to administration of the next dose. Following these
      reviews, the dose increment for subsequent groups may be increased, or the doses administered
      may be reduced, and may be lower than the starting dose. The maximum dose level to be studied
      will be 40 mg. The primary outcome measures include safety and tolerability. These outcome
      measures will be addressed in terms of occurrences of treatment-emergent AEs, changes in
      vital signs including BP and PR, SpO2, oral body temperature, ECG, spirometry (FVC, FEV1, FEV
      1%, FEV1/FVC ratio, FEF 25-75% and PEFR), physical examinations, mood assessments, and
      laboratory parameters. Secondary outcome measures will include pharmacokinetic parameters.
      These parameters will be calculated for CS-8958 and R-125489 concentrations in plasma and
      urine using a non-compartmental approach.
    

Intervention name(s): CS-8958 formulated as dry powder; Placebo
Intervention type(s): Drug; Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Prevention
Keywords: Influenza, United Kingdom