Observational Study on the Pharmacokinetics of Oseltamivir in the Treatment of Influenza During Lactation

• ClinicalTrials.gov Identifier: NCT01130636
• Recruitment Status: Completed
• First Posted: May 26, 2010
• Last Update Posted: October 8, 2012
• Sponsor: Pharmahungary Group
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Pharmahungary Group

Study Description

Brief Summary:

The main purpose of this study is to assess the potential exposure of neonates to oseltamivir during lactation by examining oseltamivir concentrations in maternal blood, urine, and breast milk in breastfeeding women who are treated with oseltamivir, an anti-flu medication.

Condition or disease	Intervention/treatment	Phase
Influenza	Drug: Oseltamivir	Phase 4

Detailed Description:

Investigational Medical Product: Tamiflu® 75 mg hard capsules

Objective: The main purpose of this study is to assess the potential neonatal exposure to oseltamivir during lactation by examining oseltamivir concentrations in maternal blood, urine, and breast milk/colostrum.

Study design: Single-country, multicenter, observational pharmacokinetic study

Enrolment and follow-up: Lactating women (up to 20 subjects) who present with clinical symptoms indicative of influenza will be recruited (a maximum of 6 months period of recruitment) to receive immediate treatment with oseltamivir (Tamiflu® 75 mg hard capsules, provided free of charges for the study) at a standard dose of 75 mg twice daily. These subjects will have a 12 hour pharmacokinetic plasma, urine and breast milk study undertaken after the steady state in oseltamivir concentrations (both active and inactive metabolites will be measured) is reached in blood, i.e. after three days after treatment. Subjects do not need laboratory confirmation of influenza infection for inclusion in this study, although the results of any virological tests that seek to confirm influenza infection will be recorded. Maternal venous blood (2 samples, one pre-dose sample and one 2.5-hours-after-dose sample), urine samples (obtained from total urine output within 12 h), and breast milk/colostrum samples (8 samples within 12 h) are taken to determine oseltamivir phosphate (inactive metabolite) and oseltamivir carboxylate (active metabolite) levels.

Safety: Adverse events (AEs) and serious adverse events (SAEs) will be recorded. SAEs will be reported to the Ethics Committee and Regulatory authorities according to the reporting requirements in Hungary.

Number of patients: A total of 20 lactating patients will be enrolled.

Number of centres: Up to 3 investigational sites in Hungary will participate in the study. All sites will belong to an academic institution.

According to the approved protocol amendment 1 (dated: 31/Aug/2010) the time schedule is the following: The patient visits are planned as soon as possible during the pandemic season in Q3-Q4 2010 and Q1-Q2 2011. The study will run until enrollment is completed and all study procedures have been completed for the last subject in 2011.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Observational Study on the Pharmacokinetics of Oseltamivir in the Treatment of Influenza During Lactation, Phase IV Trial
• Study Start Date: June 2010
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: July 2012

Arms and Interventions

Arm

Intervention/treatment

Experimental: Tamiflu; Lactating women (up to 20 subjects) who present with clinical symptoms indicative of influenza will be recruited (a maximum of 6 months period of recruitment) to receive immediate treatment with oseltamivir (Tamiflu® 75 mg hard capsules, provided free of charges for the study) at a standard dose of 75 mg twice daily. These subjects will have a 12 hour pharmacokinetic plasma, urine and breast milk study undertaken after the steady state in oseltamivir concentrations (both active and inactive metabolites will be measured) is reached in blood, i.e. after three days after treatment.

Drug: Oseltamivir; Lactating women who present with clinical symptoms indicative of influenza will receive immediate treatment with oseltamivir (Tamiflu® 75 mg hard capsules) at a standard dose of 75 mg twice daily.; Other Name: Tamiflu® 75 mg hard capsules

Outcome Measures

Primary Outcome Measures :

1. Oseltamivir phosphate and oseltamivir carboxylate concentration in venous blood, breast milk/colostrums, and urine. [ Time Frame: 12 hour period ]
   For lactating women, the plasma concentrations of oseltamivir phosphate and oseltamivir carboxylate in venous blood, breast milk/colostrums, and urine measured over a 12 hour period after three days after treatment, when the steady state in oseltamivir concentrations (both active and inactive metabolites) is reached in the blood.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. The patient is breastfeeding, or has just given birth.
2. The age of the patient is at least 18 years.
3. Written Informed Consent obtained from the patient.

4. The patient has received a diagnosis of influenza based upon the following clinical symptoms, during a time when influenza is known to be circulating:

   • fever ≥37.8oC at the time of examination or a history of fever and
   • at least one respiratory symptom (cough, coryza, sore throat, rhinitis)
5. Confirmation of infection with influenza is not required for inclusion. As H1N1v infection in pregnancy and lactation is a dangerous condition, and recommendations are that clinicians should commence antiviral therapy on an empiric basis and not wait for the results for laboratory investigations. Therefore, this study will not undertake or require any virological investigations, although these will be recorded if undertaken as part of routine care.

Exclusion Criteria:

1. Clinical suspicion of infection with a respiratory virus other than influenza and a decision by the treating physician that treatment with oseltamivir is not indicated.
2. Suspicion of invasive bacterial infection requiring immediate admission to hospital.

3. Evidence of a poorly controlled underlying medical condition, with the specific understanding that pregnancy does constitute an exclusion factor in this influenza-related study. Positive test with one of the following methods for pregnancy excludes patient from participation:

   • β-HCG blood test
   • β-HCG urine test
   • ultrasound examination confirming pregnancy.
4. Known or suspected immunosuppression (malignancy, transplant, immunosuppressive drugs)
5. Known allergy to oseltamivir.
6. Participation in any clinical trials with an investigational drug or vaccine within the previous 3 months.
7. A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the Investigator to be clinically significant and adversely affecting compliance to study drug.

Contacts and Locations

Locations

Hungary

DEOEC University of Debrecen, Clinic of Obstetrics and Gynecology

Debrecen, Hungary, H-4032

Selye János Hospital, Department of Obstetrics and Gynecology

Komárom, Hungary, 2921

Sponsors and Collaborators

Pharmahungary Group

Hoffmann-La Roche

Investigators

• Principal Investigator: Péter Vadász, MD; Selye János Hospital, Department of Obstetric and Gynecology,Komárom, Széchényi u.2. H-2921, Hungary
• Principal Investigator: Tamás Major, MD PhD; DEOEC University of Debrecen, Clinic of Obstetrics and Gynecology, Debrecen, Nagyerdei krt. 98. H-4032, Hungary
• Principal Investigator: Attila Pál, MD PhD DSc; Szeged University, Faculty of Medicine Szent-Györgyi Albert Clinical Center Clinic of Obstetrics and Gynecology
• Principal Investigator: Nándor Ács, MD PhD; Semmelweis University II. Clinic of Obstetrics and Gynecology

More Information

• Responsible Party: Pharmahungary Group
• ClinicalTrials.gov Identifier: NCT01130636
• Other Study ID Numbers: MV22970
• First Posted: May 26, 2010
• Last Update Posted: October 8, 2012
• Last Verified: October 2012

Keywords provided by Pharmahungary Group:

oseltamivir carboxylate; oseltamivir phosphate; Tamiflu pharmacokinetics in lactating women with influenza

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Oseltamivir; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action