Safety, Tolerability and Pharmacokinetic Study of Biota-CS-8958
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.
Drug: CS-8958 formulated as dry powder
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
|Official Title:||CS-8958 - A Phase I, Double-Blind, Placebo-Controlled, Ascending Single Inhaled Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Subjects|
|Study Start Date:||April 2007|
|Estimated Study Completion Date:||December 2007|
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.
|Covance Clinical Research Unit Ltd (Covance CRU)|
|Leeds, United Kingdom, LS2 9LH|