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A Pharmacokinetic/Pharmacodynamic Study of Oseltamivir in Immunocompromised Children With Confirmed Influenza Infection

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01715909
Collaborator
(none)
20
Enrollment
50
Locations
2
Arms
52.8
Actual Duration (Months)
0.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label, randomized, adaptive, 2-arm, multicenter study will evaluate the pharmacokinetics and pharmacodynamics of oseltamivir (Tamiflu) in immunocompromised children, less than (<) 13 years of age, with confirmed influenza infection. Participants will be randomized to receive either the standard dose or triple dose of oseltamivir orally daily for a minimum of 5 days and up to 20 days. Infants <1 year of age will be randomized to the standard dose arm only.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Randomized, Adaptive, Two-Arm, Multicenter Trial to Evaluate Pharmacokinetics And Pharmacodynamics of Two Doses of Oseltamivir (Tamiflu®) in The Treatment Of Influenza in Immunocompromised Children Less Than 13 Years Of Age, With Confirmed Influenza Infection
Actual Study Start Date :
Jan 22, 2014
Actual Primary Completion Date :
Jun 17, 2018
Actual Study Completion Date :
Jun 17, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Oseltamivir: Standard dose

Participants will receive standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight. Infants <1 year of age will receive oseltamivir at a dose of 3 milligrams per kilogram (mg/kg).

Drug: Oseltamivir
Participants will receive standard dose (30 to 75 milligrams [mg]) or triple standard dose (90 to 225 mg) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for </= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.
Other Names:
  • Tamiflu

    		•
    Experimental: Oseltamivir: Triple dose

    Participants will receive three times the standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight and age. Infants <1 year will receive standard dose at 3 mg/kg.

    Drug: Oseltamivir
    Participants will receive standard dose (30 to 75 milligrams [mg]) or triple standard dose (90 to 225 mg) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for </= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.
    Other Names:
  • Tamiflu

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    2. Steady State AUC0-12 of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    3. Maximum Plasma Concentration (Cmax) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    4. Cmax of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    5. Trough Plasma Concentration (Ctrough) of Oseltamivir [Pre-dose (within 30 minutes prior to administration) on Days 3 or 4]

    6. Ctrough of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration) on Days 3 or 4]

    7. Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) or Culture Testing [From randomization to negative PCR/culture test result (up to Day 50)]

    Secondary Outcome Measures

    1. Time to Resolution of Influenza Symptoms (including fever),, as Assessed by Canadian Acute Respiratory Infections Scale (CARIFS) [From randomization to resolution of all influenza symptoms (up to Day 50)]

    2. Number of Participants With Adverse Events [Baseline up to Day 50]

    3. Number of Participants With Influenza Associated Complications [Baseline up to Day 50]

    4. Number of Participants With Viral Resistance [Baseline up to Day 50]

    5. Half-life (t1/2) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    6. t1/2 of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    7. Time to Maximum Concentration (Tmax) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    8. Tmax of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    9. Elimination Rate Constant (Ke) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    10. Ke of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    11. Apparent Volume of Distribution (V/F) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    12. V/F of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    13. Apparent Clearance (CL/F) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    14. CL/F of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    15. Time to Last Measurable Concentration (Tlast) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    16. Tlast of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    17. Last Measurable Concentration (Clast) of Oseltamivir [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    18. Clast of Oseltamivir Carboxylate [Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 12 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female children, <13 years of age

    • Rapid influenza diagnostic test (RIDT), polymerase chain reaction (PCR), or viral culture positive for influenza

    • Immunocompromised

    • Symptoms/signs suggestive of influenza like illness (ILI)

    • Less than or equal to (</=) 96 hours between onset of ILI and first dose of study drug

    Exclusion Criteria:

    • Clinical evidence of severe hepatic impairment

    • Infants with post-menstrual age (PMA) <36 weeks

    • Clinical evidence of significant renal impairment

    • Allergy to oseltamivir or excipients

    • Hereditary fructose intolerance

    • Received anti-viral treatment with activity against influenza (for example amantadine, rimantadine, oseltamivir, laninamivir, peramivir, zanamivir, and ribavirin) or probenecid medication within 2 weeks prior to randomization

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Lucile Packard Child Hosp; Pediatric Pulmonary Division Palo Alto California United States 94304
    2 The Children's Hospital; Pediatric Infectious Diseases Aurora Colorado United States 80045
    3 Tufts Medical Center Boston Massachusetts United States 02111
    4 University of Minnesota Minneapolis Minnesota United States 55455
    5 SUNY Upstate Medical University Syracuse New York United States 13210
    6 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    7 Seattle Children's Hospital Seattle Washington United States 98105
    8 UZ Brussel Brussel Belgium 1090
    9 Cliniques Universitaires St-Luc Bruxelles Belgium 1200
    10 UZ Leuven Gasthuisberg Leuven Belgium 3000
    11 Hospital Erasto Gaertner Curitiba PR Brazil 81520-060
    12 Hospital São Lucas da PUCRS Porto Alegre RS Brazil 90610-000
    13 Graacc-Grupo de Apoio ao adolescente e a crianca com cancer Sao Paulo SP Brazil 04023-062
    14 Casa de Saúde Santa Marcelina São Paulo SP Brazil 08270-070
    15 Children'S Hospital of Eastern Ontario Ottawa Ontario Canada K1H 8L1
    16 Hospital For Sick Children; Infectious Disease Dept Toronto Ontario Canada M5G 1X8
    17 McGill University; Montreal Children's Hospital; Oncology Montreal Quebec Canada H4A 3J1
    18 Hospital Dr. Gustavo Fricke Viña del Mar Chile 2520000
    19 Centro Medico Imbanaco Cali Colombia
    20 Fundacion Clinica Valle de Lili, Department Rheumatology Cali Colombia
    21 Turun yliopistollinen keskussairaala Turku Finland 20520
    22 Charité - Universitätsmedizin Berlin;Klinik für Allgemeine Pädiatrie Berlin Germany 13353
    23 Universitatsklinikum Frankfurt Frankfurt Germany 60590
    24 Dr. Von Haunersches Kinderspital München Germany 80337
    25 Universitätsklinikum Münster Münster Germany 48149
    26 Universitätsklinikum Tübingen UNI-Klinik für Kinder- und Jugendmedizin Tübingen Germany 72076
    27 Childrens Regional Hospital Aglaia Kyriakou Athens Greece 115 27
    28 Aghia Sophia Children's Hospital; Pediatric Rheumatology Unit; 1st Department of Pediatrics Athens Greece 11527
    29 Rambam Medical Center Haifa Israel 31096
    30 Hadassah University Hospital - Ein Kerem Jerusalem Israel 9112001
    31 Schneider Children's Medical Center of Israel; Pediatrics Department Petach Tikva Israel 49100
    32 The Chaim Sheba Medical Center; Multiple Sclerosis Center Ramat-Gan Israel 52621
    33 The Dana Children's Hospital Tel Aviv Israel 64239
    34 Ospedale Pediatrico Bambino Gesu Roma Lazio Italy 00165
    35 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa Pediatria 1 Milano Lombardia Italy 20122
    36 ASST DI MONZA; Divisione Malattie Infettive Monza Lombardia Italy 20052
    37 Instituto Nacional de Pediatria; Departmento de Neurologia Mexico Mexico 04530
    38 Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León Monterrey Mexico 64460
    39 Uniwersyteckie Centrum Kliniczne Gdansk Poland 80-214
    40 Children Hospital, Olsztyn; Ward of Pediatric Hematology and Oncology Olsztyn Poland 10-561
    41 Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego Szczecin Poland 71-242
    42 Medical University of Silesia; Department of Pediatric Hematology and Oncology Zabrze Poland 41-800
    43 Tygerberg Hospital; Rheumatology Cape Town South Africa 7500
    44 WWCT Lakeview Hospital Johannesburg South Africa 1501
    45 Chris Hani Baragwanath Hospital Johannesburg South Africa 2013
    46 Hospital Sant Joan De Deu Esplugues De Llobregas Barcelona Spain 08950
    47 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    48 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    49 Hospital Infantil Universitario Nino Jesus Madrid Spain 28009
    50 Hospital Universitario La Paz Madrid Spain 280146

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01715909
    Other Study ID Numbers:
    • NV25719
    • 2012-002633-11
    First Posted:
    Oct 29, 2012
    Last Update Posted:
    Oct 16, 2018
    Last Verified:
    Oct 1, 2018
    Additional relevant MeSH terms:
    Influenza, Human
    Oseltamivir

    Study Results

    No Results Posted as of Oct 16, 2018