Safety and Dose Study of Peramivir for Influenza Treatment
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      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...
    

Detailed description: 
      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.
    

Intervention name(s): Peramivir
Intervention type(s): Drug
Intervention MeSH terms: Peramivir
Primary purpose: Treatment
Keywords: Influenza Virus; Avian Influenza; Normal Volunteers; Neuraminidase Inhibitor; Viral Disease; Healthy Volunteer; HV