A Pharmacokinetic Study on Co-administration of Tamiflu (Oseltamivir) and Rimantadine in Healthy Volunteers

Healthy Volunteer Clinical Trial

Official title:

An Open-label, Multiple Dose, Randomized, Three-period Crossover Study in Healthy Subjects to Evaluate the Effect of Co-administration of Oseltamivir (Ro 64-0796) 75 mg Twice Daily and Rimantadine 100 mg Twice Daily on the Pharmacokinetic Properties of Oseltamivir and Rimantadine.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172847
• Other study ID #: NP22770
• Secondary ID: 2009-012742-23
• Status: Completed
• Phase: Phase 1
• First received: July 29, 2010
• Last updated: August 17, 2016
• Start date: August 2009
• Est. completion date: February 2010

Study information

• Verified date: January 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This open label, randomized, three-period crossover study will evaluate the effect of co-administration of Tamiflu (oseltamivir) and rimantadine on the pharmacokinetics of Tamiflu and rimantadine. Healthy volunteers will receive multiple oral doses of Tamiflu, rimantadine or Tamiflu plus rimantadine in random order, with a minimum wash-out period of 7 days between treatments. Anticipated time on study is up to 11 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Adults, aged 18 to 45 years

• Healthy as judged by general physical examination, medical history, vital signs, 12-lead ECG and laboratory tests

• Body Mass Index (BMI) 18-34 kg/m2

• Willing not to participate in any other trial including an investigational drug for 3 months following the last dose

• Male subjects must agree to use a barrier contraception during the study and for 3 months after discontinuation of treatment

• Female subjects of non-child bearing potential or under effective contraception who are either post-menopausal, surgically sterile, or who agree to use barrier contraception during the whole study in addition to an intrauterine device or hormonal contraception for at least 3 months prior to 1st dose, during the study and for 3 months after discontinuation of treatment

Exclusion Criteria:

• History of or current clinically significant disease or disorder

• Positive Hepatitis B, Hepatitis C, HIV 1 or 2 test result

• Positive pregnancy test or lactating women

• Clinically relevant history of allergy or hypersensitivity

• Clinically relevant history of abuse of alcohol or other drugs; tobacco smoking is allowed (</= 10 cigarettes a day or equivalent of tobacco in cigars or pipe)

• Any major illness within 30 days prior to screening examination

• Administration of any medication during the 7 days prior to drug administration, except for paracetamol and aspirin (up to 48 hours before first dose) and oral contraceptives

• Participation in a clinical study with an investigational drug within 3 months prior to study day 1

• Donation or loss of more than 500 mL of blood within the 3 months prior to study day 1

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• oseltamivir [Tamiflu]
multiple oral doses
• rimantadine
multiple oral doses

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Oseltamivir and Oseltamivir Carboxylate	Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 of oseltamivir and oseltamivir carboxylate were calculated following the administration of oseltamivir alone or in combination with rimantadine, using the linear trapezoidal rule.	Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5	No
Primary	Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Rimantadine	AUC0-12 of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir, using the linear trapezoidal rule.	Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5	No
Secondary	Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate	Oseltamivir carboxylate is active metabolite of oseltamivir. Cmax of oseltamivir and oseltamivir carboxylate were calculated following the administration of oseltamivir alone or in combination with rimantadine and was directly observed from the data.	Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5	No
Secondary	Maximum Plasma Concentration (Cmax) of Rimantadine	Cmax of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir and was directly observed from the data.	Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5	No
Secondary	Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.	Up to 11 weeks	No
Secondary	Number of Participants With Abnormal Vital Signs	Vital signs included heart rate (HR), blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), and body temperature. Blood pressure and pulse rate were recorded when participants were rested in a supine position for at least 5 minutes and after standing for 2 minutes. Vital signs values that fall outside the investigator's normal ranges were recorded.	Screening (Days -28 to -2); pre-dose and 2h post-dose on D1 and D5 of each treatment period; at Follow-up visit (10 -14 days after last dose) for blood pressure and HR; Screening; Day -1 of each treatment period; Follow-up visit for temperature	No
Secondary	Number of Participants With Marked Abnormality in Laboratory Parameters	Laboratory analysis included hematology (hemoglobin, hematocrit, erythrocytes, platelets counts, leukocytes counts, neutrophils, eosinophils, lymphocytes, basophils, and monocytes);, biochemistry (aspartate aminotransferase , alanine aminotransferase, gamma glutamyl trans peptidase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, albumin, creatinine, urea, creatine phosphokinase, total protein, sodium, chloride, calcium, phosphate, potassium, glucose (fasting), amylase, lipase, total cholesterol, and calculated creatinine clearance); and urinalysis.; Marked laboratory test values (high and low) falling outside the marked reference range and which also represents a clinically relevant change from baseline of at least a designated amount were recoded. In this study, marked abnormality ranges for phosphate as 0.75 - 1.60 millimole (mmol)/L and proteinuria (0 to 4+, and 1).	Screening; Day -1 and Day 5 (pre-dose) of each treatment period; Follow-up visit	No
Secondary	Number of Participants With Clinically Significant or Treatment Related Changes in Electrocardiogram (ECG)	ECG was recorded when participants were rested in a supine position for at least 5 minutes.	Screening; pre-dose on Day 1 and Day 5 of each treatment period; Follow-up visit	No