Safety, Tolerability and Pharmacokinetic Study of Multiple Doses of CS-8958

Study Overview
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Brief Summary
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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
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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.

Official Title
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CS-8958 - A Phase I, Double-blind, Placebo-controlled, Ascending, Multiple Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Subjects.

Conditions
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Influenza

Intervention / Treatment
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* Drug: CS-8958
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female subjects aged 18 to 55 years, inclusive Exclusion Criteria: Pregnant or lactating female subjects. Out of range findings in vital signs, physical examination, or lab tests. Intake of any investigational drug within the 4 months prior to Day 0. Positive urine drug screen or alcohol breath test. Significant disease, event, or condition which may impact on subject safety or study compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br> | Other: Placebo<br>* Inhaled placebo<br>|
| Experimental: CS-8958 DPI<br> | Drug: CS-8958<br>* Inhaled CS-8958<br>* Other names: Laninamivir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability will be assessed via occurrences of treatment-emergent adverse events, changes in vital signs including BP, PR, SpO2, temperature, ECG, spirometry, physical examinations, and laboratory parameters |  | Duration of study |