Clinical trial NCT01172847: A Pharmacokinetic Study on Co-administration of Tamiflu (Oseltamivir) and Rimantadine in Healthy Volunteers
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-07-30
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5
measure: Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Rimantadine
timeFrame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5
measure: Maximum Plasma Concentration (Cmax) of Rimantadine
timeFrame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5
measure: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
timeFrame: Up to 11 weeks
measure: Number of Participants With Abnormal Vital Signs
timeFrame: 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
measure: Number of Participants With Marked Abnormality in Laboratory Parameters
timeFrame: Screening; Day -1 and Day 5 (pre-dose) of each treatment period; Follow-up visit
measure: Number of Participants With Clinically Significant or Treatment Related Changes in Electrocardiogram (ECG)
timeFrame: Screening; pre-dose on Day 1 and Day 5 of each treatment period; Follow-up visit
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: