Safety, Tolerability and Pharmacokinetic Study of Multiple Doses of CS-8958
Condition: Influenza
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test the safety and tolerability of an investigational
      multi-dose inhaled flu medication, CS-8958. Study participants will include 16 males and
      females, aged 18-55 years of age, inclusive. Participants will be divided into two treatment
      groups (Groups A and B) with each group consisting of 8 subjects. Participants will be
      involved in study related procedures for a maximum of 14 weeks from initial screen to the
      follow up visit. 6 subjects in Group A will be administered 40 mg of CS-8958 drug and two
      subjects will receive placebo (substance containing no medication), once a week for six
      weeks. In Group B six subjects will be administered 40 mg of CS-8958 drug and two subjects
      will receive placebo, twice a week for six weeks. Study procedures will include blood and
      urine samples, ECGs (measure of heart activity), blood pressure, pulse rate and functional
      oxygen saturation of arterial hemoglobin. Also continuous cardiac telemetry will be performed
      as well as physical examinations and spirometry assessments.
    

Detailed description: 
      Influenza is an acute febrile illness caused by influenza A and B virus affecting all age
      groups.Influenza occurs annually and each year it is estimated that influenza epidemics cause
      36,000 deaths and 114,000 hospitalizations in the US alone. Control of human influenza virus
      infections continues to be a major public health goal.Influenza infects the respiratory tract
      with a rapid onset of symptoms typically characterized by fever, chills, myalgia, headache,
      malaise, sore throat and cough. Influenza infections are generally self-limiting; however
      significant morbidity and mortality can occur, predominantly in high risk groups such as the
      elderly and those suffering from chronic conditions. It is the objective of this clinical
      trial to investigate safety and tolerability of multiple doses of CS-8958 administered via
      inhalation in healthy adult subjects. The pharmacokinetics required for this dosing regimen
      is only achievable by inhalation delivery. Study participants will include 16 males and
      females, aged 18-55 years of age, inclusive. The primary objective is to evaluate the safety
      and tolerability of 40mg CS-8958 once or twice a week (on consecutive days) for 6 weeks in
      healthy adult subjects after multiple doses administered via inhalation. The secondary
      objective is to assess the systemic exposure of CS-8958 and its active metabolite R-125489
      after single and multiple doses of CS-8958 in healthy adult subjects.

      Participants will be divided into two treatment groups (Groups A and B) with each group
      consisting of 8 subjects. Participants will be involved in study related procedures for a
      maximum of 14 weeks from initial screen to the follow up visit. 6 subjects in Group A will be
      administered 40 mg of CS-8958 drug and two subjects will receive placebo (substance
      containing no medication, once a week for six weeks. In Group B six subjects will be
      administered 40 mg of CS-8958 drug and two subjects will receive placebo, twice a week for
      six weeks.

      Adverse events will be recorded at every visit. Vital signs including blood pressure, pulse
      rate and functional oxygen saturation of arterial hemoglobin will be measured on admission,
      pre-dose and at multiple time points post each dose. ECGs will be performed on admission,
      pre-dose and at multiple time points post each dose.Continuous cardiac telemetry will be
      performed for 24 hours post first dose each week for cohort A and 60 hours post first dose
      each week for cohort B. Spirometry assessments including forced vital capacity, forced
      expiratory volume in 1 second, forced expiratory volume percentage in 1 second, forced
      expiratory flow rate, and peak expiratory flow rate will be performed on admission, pre-dose
      and at multiple time points post dose. Physical examinations will be performed on Day -1 and
      at the final visit (and as needed if subject develops symptomatology). Blood samples for
      hematology and biochemistry assessments will be taken on admission, and 24 hours post dose
      each week. Urine samples for urinalysis tests will be collected on admission, and 24 hours
      post dose each week. Blood samples for pharmacokinetic testing will be taken pre-dose and at
      multiple time points post each dose.

      The Safety Monitoring Committee (SMC) will review the safety, tolerability and
      pharmacokinetic data from Cohort A prior to beginning Cohort B.
    

Intervention name(s): CS-8958; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Inhaled CS-8958; Inhaled placebo
Other intervention name(s): Laninamivir
Intervention MeSH terms: Laninamivir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment