Clinical trial NCT01728753: T-705a Multicenter Study in Adults Subjects With Uncomplicated Influenza
Official title: Randomized, Double Blind,Placebo-Controlled, Multicenter Study Evaluating the Safety and Pharmacokinetics of Different Dosing Regimens of Favipiravir in Healthy Adult Subjects and Adult Subjects With Uncomplicated Influenza
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza
Lead sponsor: MDVI, LLC
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2012-11-20
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is safety and pharmacokinetics (PK) of favipiravir study in adults 18-80 years of age diagnosed with uncomplicated influenza.


Eligibility criteria: Inclusion Criteria:

1. Understand the requirements of the study and has provided written informed consent prior to undergoing any study-related procedures.
2. Is male or female between the ages of 18 and 80 years old, inclusive.
3. Tests positive for influenza A or B by a commercially available Rapid Antigen Test (RAT) -OR- Has influenza confirmed by diagnostic assay (e.g. non-study RAT or PCR) from another clinic during the 48 hours between onset of symptoms and anticipated dosing.

   (Note: A subject with a negative RAT result may still enroll if the Medical Monitor and Investigator agree that there is a known influenza outbreak circulating in the community or the subject has been in close contact with a person who was recently confirmed to have influenza by RAT or another lab test).
4. Has a fever, defined for subjects ≥18 but ≤65 years old as a temperature (oral) of 100.4°F (38.0°C) or more; subjects \>65 years old with a temperature (oral) of 100.0°F (37.8°C) or more at the first visit or in the 6 hours prior if antipyretics were taken before the visit.
5. If male, subject must:

   a. Be sterile (have had a vasectomy at least 6 months prior to Day 1 dosing and had sperm counts verifying that he is no longer fertile) OR b. Agree he will not donate sperm during the study and for 3 months following the last dose of study medication, and c. Will strictly adhere to the following contraceptive measures for 3 months after the last dose of study medication: i. Abstain from sexual intercourse or; ii. Use a condom during sexual intercourse with a female of child-bearing potential. In addition to the male condom, the female partner must use another form of contraception (e.g. intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal implants) for at least 3 months following Day 1 dosing).
6. If female, subject must:

   a. Be unable to bear children (have not had a period for ≥12 consecutive months, have had her uterus or ovaries removed, or have had a tubal ligation) OR b. Have a male partner incapable of fathering a child (has had a vasectomy at least 6 months prior to study entry and has had sperm counts verifying that he is no longer fertile) OR c. Have a negative urine pregnancy test at screening AND d. Not have had unprotected sex within the last month AND e. If she is of childbearing potential, will strictly adhere to the following contraceptive measures during the study and for 3 months following the last dose of study medication: i. Abstain from sexual intercourse or ii. Her male partner agrees to use a condom during sexual intercourse AND iii. She agrees to use an approved method of contraception (e.g., IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal implants).
7. Has 2 or more of the following symptoms (moderate to severe in intensity) at the time of enrollment that began 48 hours or less prior to first dose:

   1. Cough
   2. Sore throat
   3. Headache
   4. Nasal congestion
   5. Body aches and pains
   6. Fatigue

Influenza Symptom Intensity:

0: None

1. Mild, Symptoms are tolerable, possible to perform daily activities
2. Moderate, Symptoms are disturbing, partially interfere with daily activities
3. Severe, Symptoms are intolerable, impossible to perform daily activities

Exclusion Criteria:

1. Has taken an anti-influenza drug (e.g., amantadine hydrochloride, rimantadine, oseltamivir phosphate, zanamivir hydrate, or peramivir) or live vaccination within 4 weeks prior to signing of the informed consent.
2. Has underlying chronic respiratory disease (e.g., Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, diffuse panbronchiolitis, bronchiectasis, pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or active tuberculosis).
3. At the beginning of the study, is suspected of having bacterial respiratory infection (i.e., expectoration of purulent or mucopurulent sputum and/or infiltrate in lung in a chest x-ray, or is on antibiotics for lung disease).
4. Has a history of gout or is under treatment for gout or hyperuricemia.
5. Has hereditary xanthinuria.
6. Has a history of hypouricemia (under 1 mg/dL) or xanthine calculi of the urinary tract.
7. Has a history of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase.
8. Is using adrenocorticosteroids, except topical preparations, or immunosuppressive drugs (e.g., immunosuppressants, anticancer drugs).
9. Has an allergy to acetaminophen or has a contraindication for acetaminophen.
10. Has a serious chronic disease (e.g., HIV, cancer requiring chemotherapy within the preceding 6 months, moderate or severe hepatic insufficiency and/or unstable renal, cardiac, pulmonary, neurologic, vascular, or endocrinologic disease states requiring medication dose adjustments within the last 30 days).
11. Has previously received favipiravir (T-705a).
12. Has renal insufficiency requiring hemodialysis or central auditory processing disorder (CAPD).
13. Has a Class II or greater cardiac impairment defined by the New York Heart Association (NYHA)Functional Classification.
14. Has a history of alcohol or drug abuse in the preceding 2 years.
15. Has a psychiatric disease that is not well controlled (not on a stable regimen for greater than one year)
16. Has taken another investigational drug within 30 days prior to signing the informed consent.
17. Is deemed by the Investigator to be ineligible for any reason.
18. Is employed by or is related to an employee of the clinical study site.
19. Female patients who are pregnant, breast-feeding, or have a positive urine pregnancy test at Visit 1.

Primary outcomes:
measure: Cmax of favipiravir
timeFrame: Post-dose on Days 1 and 5: 1, 2, 4, 9, 10, and 12 hours
measure: Area Under the Curve (AUC) of favipiravir
timeFrame: Post-dose on Days 1 and 5: 1, 2, 4, 9, 10, and 12 hours
Secondary outcomes:
measure: time to alleviation of influenza symptoms
timeFrame: 15 days
measure: Adverse Event[AE]
timeFrame: 15 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
Study officials:
affiliation: Sunrise Medical Research, Lauderdale Lakes, FL 33319
name: Jason M Hafizullah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Riverside Clinical Research, Edgewater, FL 32132
name: Susan Hole, D.O.
role: PRINCIPAL_INVESTIGATOR
affiliation: Health Concepts, Rapid City, SD 57702
name: Richard L. Beasley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oakland Medical Research Center, Troy, MI 48085
name: Jay H Sandberg, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Holy Trinity Medical Clinic, Harbor City, CA 90710
name: Edgardo A. Osea, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HCCA Clinical Research Solutions, Columbia, TN 38401
name: Shawn N. Gentry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Burke Primary Care, Morganton, NC 28655
name: Stephen K. Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Institute of South Florida, Inc., Miami, FL 33173
name: Roberto Sotolongo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Torrance Clinical Research Institute Inc., Lomita, CA 90717
name: Marina Raikhel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asthma & Allergy Center, Toledo, OH 43617
name: Syed M. Rehman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Integrated Clinca Trial Services Inc., West Des Moines, IA 50265
name: Jeffrey Lenz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: APF Research LLC, Miami, FL 33135
name: Jorge L. Santander, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Meridian Clinical Research, Bellevue, NE 68005
name: James A. Cervantes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Center of Fresno, Inc., Fresno, CA 93726
name: Hipolito G. Mariano Jr., MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Field of Dreams PC, dba Bozeman Urgent Care Center, Bozeman, MT 59715
name: John M. Wise, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associated Pharmaceutical Research Center, Inc., Buena Park, CA 90620
name: Mercedes B. Samson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Joseph's Medical Associates, Stockton, CA 95204
name: Shaukat A. Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pioneer Clinical Research LLC, Bellevue, NE 68005
name: Darin Gregory, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asthma and Allergy Research Associates, Upland, PA 19013
name: Sandra M. Gawchik, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Fay West Family Practice, Scottdale, PA 15683
name: Tiffany M. Pluto, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: HCCA Clinical Research Solutions, Franklin, TN 37067
name: Rennee N. Dhillon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pinnacle Research Group LLC, Anniston, AL 36207
name: Almena L. Free, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: South Florida Research Phase I-IV, Inc., Miami, FL 33165
name: Esperanza Arce-Nunez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Trials of America, Inc., Winston Salem, NC 27103
name: Robert D. Rosen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lovelace Scientific Resources, Inc., Venice, FL 34292
name: Charles M. Schwarz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Marcus Research Clinic Inc., Miami, FL 33015
name: Idalia A. Acosta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cherry Tree Medical Associates/Alternative Clinical Trials LLC, Uniontown, PA 15401
name: Kishor E. Joshi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diversified Medical Practices, P.A., Houston, TX 77057
name: Patricia D. Salvato, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HCCA Clinical Research Solutions, New York, NY 10016
name: Lawrence P. Schwartz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montana Health Research Institute Inc., Billings, MT 59102
name: Michael C. Hagan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dayton Clinical Research, Dayton, OH 45406
name: Martin J. Schear, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MD Medical Research, Oxon Hill, MD 20745
name: Stephen Ong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Trials Of America Inc., Shreveport, LA 71105
name: April Palmer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Highland Clinical Research, Salt Lake City, UT 84124
name: Derek D. Muse, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Community Research of South Florida, Hialeah, FL 33016
name: Jose M. Carpio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Holy Name Medical Center, Teaneck, NJ 07666
name: Thomas M Birch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cahaba Research, Birmingham, AL 35242
name: Barry K McLean, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Novo Research Inc., Highland Heights, KY 41076
name: Barry N Heller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Little Rock Allergy & Asthma Clinical Research Center, Little Rock, AR 72205
name: Karl V Sitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Midwest Allergy and Asthma Clinic, P.C., Omaha, NE 68130
name: Thomas C Nilsson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Trial Connection, Flagstaff, AZ 86001
name: Douglas W Mapel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: DeGarmo Institute of Medical Research, Greer, SC 29651
name: Ronald G DeGarmo, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Clinical Research, North Hollywood, CA 91606
name: Teresa S Sligh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HealthCare Partners Medical Group LLC, Los Angeles, CA 90015
name: Gary L Sutter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Integrated Medical Research, PC, Ashland, Oregon 97520
name: John P Delgado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: American Health Network of IN, LLC, Avon, IN 46123
name: Ronald K Stegemoller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Global Clinical Professionals, Miami, FL 33156
name: Edgar A Marin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Acadia Clinical Research, LLC, Bangor, Maine 04401
name: Marie R Albert, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Advanced Clinical Research Inc., Meridian, ID 83642
name: Mark A Turner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heartland Research Associates, LLC, Wichita, KS 67207
name: Terry L Poling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Comprehensive Clinical Research, Berlin, NJ 08009
name: David R Hassman, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Professional Research Network of Kansas, LLC, Wichita, KS 67203
name: William C Simon, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin La Crosse, La Crosse, WI 54601
name: Brian K Allen, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: North Alabama Research Center LLC, Athens, Alabama 35611
name: Ernest L Hendrix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HCCA Clinical Research Solutions, Middleburg Heights, OH 44130
name: John A Panuto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: HCCA Clinical Research Solutions, Smyrna, TN 37167
name: Sadia Dar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: North Central Arkansas Medical Associates, Mountain Home, AZ 72653
name: Michael E Hodges, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Physicians Quality Care, Jackson, TN 38305
name: Melanie Hoppers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lakeview Medical Research, Summerfield, FL 34491
name: Khai S Chang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Best Quality Research, Hialeah, FL 33016
name: Arles Perdomo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Quick Care Medical, Hamilton, NJ 08690
name: Neerja Misra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Urgent Care Specialist, LLC DBA Hometown Urgent Care & Occupational Health, Dayton, OH 45432
name: Steve Choi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRC Clinics, Towson, MD 21204
name: Gregory Pokrywka, MD
role: PRINCIPAL_INVESTIGATOR
References: