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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01172847
First received: July 29, 2010
Last updated: February 19, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Healthy Volunteer
Drug: oseltamivir [Tamiflu]
Drug: rimantadine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
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.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Oseltamivir and Oseltamivir Carboxylate [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 ] [ Designated as safety issue: No ]
    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.

  • Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Rimantadine [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 ] [ Designated as safety issue: No ]
    AUC0-12 of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir, using the linear trapezoidal rule.


Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 ] [ Designated as safety issue: No ]
    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.

  • Maximum Plasma Concentration (Cmax) of Rimantadine [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 ] [ Designated as safety issue: No ]
    Cmax of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir and was directly observed from the data.

  • Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) [ Time Frame: Up to 11 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Abnormal Vital Signs [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Marked Abnormality in Laboratory Parameters [ Time Frame: Screening; Day -1 and Day 5 (pre-dose) of each treatment period; Follow-up visit ] [ Designated as safety issue: No ]

    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).


  • Number of Participants With Clinically Significant or Treatment Related Changes in Electrocardiogram (ECG) [ Time Frame: Screening; pre-dose on Day 1 and Day 5 of each treatment period; Follow-up visit ] [ Designated as safety issue: No ]
    ECG was recorded when participants were rested in a supine position for at least 5 minutes.


Enrollment: 24
Study Start Date: August 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: oseltamivir [Tamiflu]
multiple oral doses
Active Comparator: B Drug: rimantadine
multiple oral doses
Experimental: C Drug: oseltamivir [Tamiflu]
multiple oral doses
Drug: rimantadine
multiple oral doses

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01172847

Locations
United States, Arkansas
Little Rock, Arkansas, United States, 72204
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01172847     History of Changes
Other Study ID Numbers: NP22770  2009-012742-23 
Study First Received: July 29, 2010
Results First Received: January 5, 2016
Last Updated: February 19, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Oseltamivir
Rimantadine
Anti-Infective Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 04, 2016