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

NCT01715909 | Completed Phase 1

• 2 other identifiers: NV257192012-002633-11
• Study Type: interventional
• Target: 20
• Locations: 15 countries
• Sites: 50

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.

Conditions

Influenza

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• Cmax of Oseltamivir Carboxylate

  Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

• Trough Plasma Concentration (Ctrough) of Oseltamivir

  Pre-dose (within 30 minutes prior to administration) on Days 3 or 4

• Ctrough of Oseltamivir Carboxylate

  Pre-dose (within 30 minutes prior to administration) on Days 3 or 4

• 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 Outcomes (18)

• 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)

• Number of Participants With Adverse Events

  Baseline up to Day 50

• Number of Participants With Influenza Associated Complications

  Baseline up to Day 50

• Number of Participants With Viral Resistance

  Baseline up to Day 50

• 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

Study Arms (2)

Oseltamivir: Standard dose

EXPERIMENTAL

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

Oseltamivir: Triple dose

EXPERIMENTAL

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

Interventions

Oseltamivir DRUG

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.

Also known as: Tamiflu

Oseltamivir: Standard dose; Oseltamivir: Triple dose

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (50)

Lucile Packard Child Hosp; Pediatric Pulmonary Division

Palo Alto, California, 94304, United States

Location

The Children's Hospital; Pediatric Infectious Diseases

Aurora, Colorado, 80045, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Hospital Erasto Gaertner

Curitiba, Paraná, 81520-060, Brazil

Location

Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Graacc-Grupo de Apoio ao adolescente e a crianca com cancer

São Paulo, São Paulo, 04023-062, Brazil

Location

Casa de Saúde Santa Marcelina

São Paulo, São Paulo, 08270-070, Brazil

Location

Children'S Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital For Sick Children; Infectious Disease Dept

Toronto, Ontario, M5G 1X8, Canada

Location

McGill University; Montreal Children's Hospital; Oncology

Montreal, Quebec, H4A 3J1, Canada

Location

Hospital Dr. Gustavo Fricke

Viña del Mar, 2520000, Chile

Location

Centro Medico Imbanaco

Cali, Colombia

Location

Fundacion Clinica Valle de Lili, Department Rheumatology

Cali, Colombia

Location

Turun yliopistollinen keskussairaala

Turku, 20520, Finland

Location

Charité - Universitätsmedizin Berlin;Klinik für Allgemeine Pädiatrie

Berlin, 13353, Germany

Location

Universitatsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Dr. Von Haunersches Kinderspital

München, 80337, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen UNI-Klinik für Kinder- und Jugendmedizin

Tübingen, 72076, Germany

Location

Childrens Regional Hospital Aglaia Kyriakou

Athens, 115 27, Greece

Location

Aghia Sophia Children's Hospital; Pediatric Rheumatology Unit; 1st Department of Pediatrics

Athens, 11527, Greece

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

Location

Schneider Children's Medical Center of Israel; Pediatrics Department

Petah Tikva, 49100, Israel

Location

The Chaim Sheba Medical Center; Multiple Sclerosis Center

Ramat Gan, 52621, Israel

Location

The Dana Children's Hospital

Tel Aviv, 64239, Israel

Location

Ospedale Pediatrico Bambino Gesu

Rome, Lazio, 00165, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa Pediatria 1

Milan, Lombardy, 20122, Italy

Location

ASST DI MONZA; Divisione Malattie Infettive

Monza, Lombardy, 20052, Italy

Location

Instituto Nacional de Pediatria; Departmento de Neurologia

México, 04530, Mexico

Location

Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León

Monterrey, 64460, Mexico

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Children Hospital, Olsztyn; Ward of Pediatric Hematology and Oncology

Olsztyn, 10-561, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego

Szczecin, 71-242, Poland

Location

Medical University of Silesia; Department of Pediatric Hematology and Oncology

Zabrze, 41-800, Poland

Location

Tygerberg Hospital; Rheumatology

Cape Town, 7500, South Africa

Location

WWCT Lakeview Hospital

Johannesburg, 1501, South Africa

Location

Chris Hani Baragwanath Hospital

Johannesburg, 2013, South Africa

Location

Hospital Sant Joan De Deu

Esplugues de Llobregas, Barcelona, 08950, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 280146, Spain

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 29, 2012
• Study Start: January 22, 2014
• Primary Completion: June 17, 2018
• Study Completion: June 17, 2018
• Last Updated: October 16, 2018

Record last verified: 2018-10

Locations

CO (2); PL (4); IT (3); FI (1); CA (3); ES (5); GR (2); IL (5); DE (5); ME (2); US (7); ZA (3); BR (4); CL (1); BE (3)