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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01715909
• Other study ID #: NV25719
• Secondary ID: 2012-002633-11
• Status: Completed
• Phase: Phase 1
• Start date: January 22, 2014
• Est. completion date: June 17, 2018

Study information

• Verified date: October 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 17, 2018
• Est. primary completion date: June 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

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.

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Hospital Erasto Gaertner	Curitiba	PR
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	RS
Brazil	Graacc-Grupo de Apoio ao adolescente e a crianca com cancer	Sao Paulo	SP
Brazil	Casa de Saúde Santa Marcelina	São Paulo	SP
Canada	McGill University; Montreal Children's Hospital; Oncology	Montreal	Quebec
Canada	Children'S Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Hospital For Sick Children; Infectious Disease Dept	Toronto	Ontario
Chile	Hospital Dr. Gustavo Fricke	Viña del Mar
Colombia	Centro Medico Imbanaco	Cali
Colombia	Fundacion Clinica Valle de Lili, Department Rheumatology	Cali
Finland	Turun yliopistollinen keskussairaala	Turku
Germany	Charité - Universitätsmedizin Berlin;Klinik für Allgemeine Pädiatrie	Berlin
Germany	Universitatsklinikum Frankfurt	Frankfurt
Germany	Dr. Von Haunersches Kinderspital	München
Germany	Universitätsklinikum Münster	Münster
Germany	Universitätsklinikum Tübingen UNI-Klinik für Kinder- und Jugendmedizin	Tübingen
Greece	Aghia Sophia Children's Hospital; Pediatric Rheumatology Unit; 1st Department of Pediatrics	Athens
Greece	Childrens Regional Hospital Aglaia Kyriakou	Athens
Israel	Rambam Medical Center	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Schneider Children's Medical Center of Israel; Pediatrics Department	Petach Tikva
Israel	The Chaim Sheba Medical Center; Multiple Sclerosis Center	Ramat-Gan
Israel	The Dana Children's Hospital	Tel Aviv
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa Pediatria 1	Milano	Lombardia
Italy	ASST DI MONZA; Divisione Malattie Infettive	Monza	Lombardia
Italy	Ospedale Pediatrico Bambino Gesu	Roma	Lazio
Mexico	Instituto Nacional de Pediatria; Departmento de Neurologia	Mexico
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León	Monterrey
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Children Hospital, Olsztyn; Ward of Pediatric Hematology and Oncology	Olsztyn
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego	Szczecin
Poland	Medical University of Silesia; Department of Pediatric Hematology and Oncology	Zabrze
South Africa	Tygerberg Hospital; Rheumatology	Cape Town
South Africa	Chris Hani Baragwanath Hospital	Johannesburg
South Africa	WWCT Lakeview Hospital	Johannesburg
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Universitario La Paz	Madrid
United States	The Children's Hospital; Pediatric Infectious Diseases	Aurora	Colorado
United States	Tufts Medical Center	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Minnesota	Minneapolis	Minnesota
United States	Lucile Packard Child Hosp; Pediatric Pulmonary Division	Palo Alto	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Finland,  Germany,  Greece,  Israel,  Italy,  Mexico,  Poland,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Cmax of Oseltamivir Carboxylate		Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Primary	Trough Plasma Concentration (Ctrough) of Oseltamivir		Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
Primary	Ctrough of Oseltamivir Carboxylate		Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
Primary	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	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)
Secondary	Number of Participants With Adverse Events		Baseline up to Day 50
Secondary	Number of Participants With Influenza Associated Complications		Baseline up to Day 50
Secondary	Number of Participants With Viral Resistance		Baseline up to Day 50
Secondary	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
Secondary	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
Secondary	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
Secondary	Tmax of Oseltamivir Carboxylate		Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Secondary	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
Secondary	Ke of Oseltamivir Carboxylate		Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Tlast of Oseltamivir Carboxylate		Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
Secondary	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
Secondary	Clast of Oseltamivir Carboxylate		Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4