A Study to Assess the Safety, Tolerability and Pharmacokinetics of AVI-7537 in Healthy Adult Volunteers

This study has been withdrawn prior to enrollment.
(Terminated for convenience of the Government due to funding constraits)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sarepta Therapeutics
ClinicalTrials.gov Identifier:
NCT01593072
First received: May 3, 2012
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to evaluate the safety and tolerability of healthy male and female subjects with intravenous (IV) infusions of AVI 7537 compared to matched placebo in and to evaluate the pharmacokinetics (PK).


Condition Intervention Phase
Ebola Hemorrhagic Fever
Drug: AVI-7537
Other: Normal Saline Solution (NSS)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Dose-Escalation A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of AVI-7537 in Healthy Adult Volunteers

Resource links provided by NLM:


Further study details as provided by Sarepta Therapeutics:

Primary Outcome Measures:
  • The outcome measures are Serial PK Day 1 over 24 hrs(pre-dose,10 min post,30 min post, 1hr 1.5,2,4,6, 8, 12,16,24,28,32,36, and 48 hrs post-dose), daily through level and on Day 14 (last day of dosing) serial PK until 48 hrs post last dose. [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    The outcome measures are Serial PK Day 1 over 24 hours (pre-dose, 10 minutes post-dose , 30 minutes, 1 hour, 1.5, 2, 4, 6,. 8, 12,16,24 hours post-dose), daily trough level and on Day 14 (last day of dosing). PK Day 14 over 48 hours (post-dose, 10 minutes, 1.5, 2, 4, 6, 8, 12, 16, 24, 28, 32, 36, and 48 hours post-dose (collection of plasma pre-dose on Day 14 will also serve as the trough sample for that day).


Secondary Outcome Measures:
  • To evaluate the pharmacokinetics (PK) of 14 once daily doses of AVI-7537 in healthy male and female subjects, [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Efficacy will not be assessed in a Phase I study.


Enrollment: 0
Study Start Date: August 2012
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AVI-7537
AVI-7537
Drug: AVI-7537

Cohort 1: AVI-7537 at 4.5 mg/kg IV; Cohort 2: AVI-7537 at 9 mg/kg IV;Cohort 3: AVI-7537 at 15 mg/kg IV; Cohort 4: AVI-7537 at 30 mg/kg IV

The amount of AVI-7537 required to administer the required dose will be diluted to a volume of approximately 150 mL with normal saline solution (NSS) and given by IV infusion over 30 minutes once a day for 14 days. Infusions will be administered at approximately the same time each day.

Other Name: AVI-7537
Placebo
Normal Saline Solution (NSS)
Other: Normal Saline Solution (NSS)
Normal Saline Solution (NSS)
Other Name: Normal Saline Solution (NSS)

Detailed Description:

The purpose of this study is to evaluate the safety and tolerability of 14 once daily intravenous (IV) infusions of ascending doses of AVI 7537 compared to matched placebo in healthy male and female subjects.

To evaluate the pharmacokinetics (PK) of 14 once daily doses of AVI-7537 in healthy male and female subjects

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

A subject must meet all of the following criteria to be eligible for this study.

  1. Man or woman 18 to 50 years of age, inclusive, at the time of screening.
  2. Body mass index 18 kg/m2 to 35 kg/m2, inclusive, at the time of screening and Check-in (Day -1).
  3. Good general health (no chronic health conditions) as determined by the Investigator.
  4. Female subjects must be of non-childbearing potential (e.g., be confirmed post-menopausal or have undergone surgical sterilization) or must, in conjunction with their sexual partner(s), use 2 forms of medically acceptable contraception (e.g., oral contraception in conjunction with a male condom) during the screening period and for the entire duration of the study including the 28-day post last dose follow-up.
  5. Male subjects must either be sterile or agree to use, for the entire duration of the study including the 28 day post last dose follow-up, a male condom and the female sexual partner must also use a medically acceptable form of birth control (e.g. oral contraceptives).
  6. Male subjects must agree to not donate sperm for at least 30 days after the last infusion of study medication.
  7. Able to understand the requirements of the study, to provide written informed consent (as evidenced by signature on an informed consent document that is approved by an Institutional Review Board [IRB]), and agreeable to abiding by the study restrictions.

Exclusion Criteria:

A subject who meets any of the following criteria will be excluded from this study.

  1. Pregnancy or breastfeeding.
  2. A positive urine or blood screen for drugs of abuse, including alcohol.
  3. Use of any tobacco- or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to Check-in (Day -1).
  4. A positive cotinine test indicating recent nicotine use.
  5. Donated blood within 90 days or plasma within 30 days of first dose on Day 1.
  6. Active substance abuse or any medical or psychiatric condition that could jeopardize the subject's safety or the subject's ability to comply with the protocol.
  7. Use of any medications apart from vitamins, acetaminophen, or hormonal contraception within 14 days of first dose on Day 1. Subjects with mild seasonal allergies may use antihistamines at the discretion of the Investigator after approval by the Sponsor Medical Monitor.
  8. Participation in any interventional clinical trial within 45 days of first dose on Day 1 (i.e., received any other investigational drug).
  9. Recipient of an organ transplant (solid or hematopoietic).
  10. Prolonged QTcF interval > 440 ms for males or > 460 ms for females using the average of the triplicate electrocardiograms (ECGs) collected during screening, on Day -1, or just prior to dosing on Day 1.
  11. Other clinically significant ECG abnormality, as determined by the Investigator.
  12. Any clinically significant abnormal hematology, chemistry, coagulation, or urinalysis value, as determined by the Investigator.
  13. Glomerular filtration rate (GFR) of < 80 mL/min, based on the Modification of Diet in Renal Disease equation.
  14. Urine-albumin-to-creatinine ratio (UACR) > 30 mg/g.
  15. Positive test for human immunodeficiency virus (HIV-1 serology) or known HIV infection.
  16. Positive result for hepatitis B surface antigen (HBsAg) or for hepatitis C virus (HCV) antibody.
  17. Use of alcohol-containing foods or beverages within 72 hours prior to Check-in on Day -1.
  18. Use of caffeine-containing foods or beverages within 24 hours prior to Check-in on Day -1.
  19. Febrile illness or significant infection within 48 hours before administration of the first dose of study drug on Day 1.

Note: Inclusion of each subject will be reviewed with a member of AVI BioPharma Clinical Personnel prior to enrollment in the trial. Written approval from a member of AVI BioPharma Clinical Personnel is required prior to randomization.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593072

Locations
United States, Kansas
Quintiles Phase I Services
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
Sarepta Therapeutics
Investigators
Principal Investigator: Alison Heald, MD Sarepta Therapeutics
  More Information

No publications provided

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT01593072     History of Changes
Other Study ID Numbers: 7537-us-101, W9113M-10-C-0056
Study First Received: May 3, 2012
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sarepta Therapeutics:
Multiple Ascending Dose (MAD)
Ebola Virus
Post Exposure Prophylaxis
EHF

Additional relevant MeSH terms:
Hemorrhagic Fever, Ebola
Hemorrhagic Fevers, Viral
Filoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014