Safety and Dose Study of Peramivir for Influenza Treatment
This study will evaluate the safety and tolerability of peramivir, a new drug to treat influenza. The study will administer gradually increasing doses of the drug in successive small groups of subjects to determine the optimal dose that is safe and well tolerated. It will be studied first at a single dose and then in multiple doses. The study will also determine how long peramivir stays in the body and how high the drug levels are in the blood.
Men and women 18 - 40 years of age who weigh at least 110 lbs. and have a body mass index (BMI) between 19 and 32 may be eligible for this study. Candidates are screened with a medical history, physical examination, electrocardiogram (EKG), and blood and urine tests.
Part I - Single Dose Escalation
Participants are admitted to the NIH hospital for 32 to 40 hours for a single 15-minute intravenous infusion of peramivir or placebo (saline), followed by monitoring and evaluation. The drug dose is increased in successive groups of eight subjects; in each group, six subjects are given peramivir and two receive placebo. The first group receives 0.5 mg/kg of peramivir; subsequent groups receive increasingly higher doses (1, 2, 3.5, and 5 mg/kg) as long as the last dose was well tolerated by the preceding group. Blood samples are drawn and subjects are monitored for vital signs (temperature, blood pressure and heart rate) and for symptoms such as headache, nausea, shortness of breath or pain at 0.5, 1, 2, 3, 6, 9, 12, 18 and 24 hours after the drug infusion. At the 24-hour evaluation they have an EKG. If needed, an echocardiogram (ultrasound examination of the heart) may also be done. Subjects return to the clinic 2, 3, 7, 14, and 28 days after the infusion for a check of vital signs, review of symptoms, blood draw, and urine sample collection. In addition, subjects are asked to collect all their urine for the first 48 hours after the study drug infusion.
Part II - Multi-dose Escalation
Groups of 16 subjects receive an intravenous infusion of peramivir (12 subject) or placebo (4 subjects) once a day for 5 consecutive days. The first four infusions are given in the NIH outpatient clinic. The dose of peramivir is increased in successive groups of 16 subjects as long as the preceding dose was well tolerated. Before the infusion on day 1, subjects have a physical examination, blood test and EKG to obtain baseline values. After the infusion, they remain in the hospital for 6 hours. Vital signs and symptoms are c...
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Double-Blind, Placebo-Controlled, Dose-Escalating Study to Evaluate the Safety and Tolerability of Intravenous Peramivir in Healthy Subjects|
|Study Start Date:||February 2006|
|Study Completion Date:||November 2006|
|Primary Completion Date:||November 2006 (Final data collection date for primary outcome measure)|
Human influenza is a serious disease causing over 30,000 deaths in the United States each year, and avian influenza presents a threat of a future pandemic. Despite this burden of current and potential disease, there are no parenteral treatments for influenza, and currently, the most common treatment (oseltamivir) is expensive and complex to manufacture.
The primary purpose of this protocol is to evaluate the safety and tolerability of intravenous peramivir, a neuraminidase inhibitor. Beginning with a low single-dose, the safety and tolerability is established by evaluating symptoms, clinical laboratory tests, ECG, and pharmacokinetics. Utilizing a series of stopping rules and a medical monitor, the dose will be escalated as safety and tolerability are established. Once the maximum tolerated dose (MTD) is established in the first part of this trial (either limited by adverse effects or up to maximum anticipated dose), the safety and tolerability of multi-dose administration will begin (replicating anticipated clinical use). These cohorts will be evaluated using similar criteria. The dose used in the multi-dose cohorts will also be escalated as safety and tolerability are established.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|