A Single Dose Study of Tamiflu in Volunteers in Dialysis And in Volunteers With Reduced Creatinine Clearance

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01556633
First received: March 15, 2012
Last updated: May 26, 2016
Last verified: May 2016
  Purpose
This open-label, prospective, single dose study will evaluate the pharmacokinetics and safety of Tamiflu (oseltamivir) in volunteers on dialysis and in volunteers with a creatinine clearance from 10 to 30 mL/min. Volunteers will receive a single oral dose of Tamiflu.

Condition Intervention Phase
Healthy Volunteer
Drug: Tamiflu (oseltamivir)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Prospective, Single Oral Dose Study Evaluating the Pharmacokinetics, Safety, and Tolerability of Oseltamivir in Adult Subjects on Peritoneal Dialysis (PD) Using a Rapid Cycle Regimen to Simulate APD and in Adult Subjects With Creatinine Clearance From 10 to 30 mL/Min Not on Dialysis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Total Dialysate Clearance for Automated Peritoneal Dialysis (CLDAPD) of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose [ Time Frame: CCPD: pre-dose (0)-2.67, 2.67-5.33, 5.33-8; CAPD: 8-16, 16-24; CCPD: 24-26.67, 26.67-29.33, 29.33-32; CAPD: 32-40, 40-48 hrs post-dose for urine; CCPD and CAPD:0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48 hrs post-dose for blood ] [ Designated as safety issue: No ]

    CLDAPD is the total dialysate clearance for automated peritoneal dialysis, attributable to both continuous cycler-assisted peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD), which was calculated with the recovery method over the dense blood sampling collection interval from 0 to 48 hours post-dose.

    CLDAPD = the amount excreted into dialysate from 0 to 48 hours (Aed[0-48])/ plasma area under the concentration-time curve from time zero through 48 hours (AUC[0-48])

    CLDCCPD = mean of CLDCCPD from the 2 CCPD sessions, calculated as CLDCCPD = (Aed[0-8]/AUC[0-8] + Aed[24-32]/AUC[24-32]) / 2

    CLDCAPD = mean of CLDCAPD from the 3 CAPD sessions, calculated as CLDCAPD = (Aed[8-16]/AUC[8-16] + Aed[16-24]/AUC[16-24] + Aed[32-48]/AUC[32-48]) / 3


  • AUC120, AUC168 and AUCinf of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose [ Time Frame: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose ] [ Designated as safety issue: No ]
    AUC120 is defined as the area under the plasma concentration-time curve from time zero through 120 hours post-dose, AUC168 is defined as the area under the plasma concentration-time curve from time zero through 168 hours post-dose, and AUCinf is defined as the area under the plasma concentration-time curve from time zero extrapolated to infinity. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.

  • AUCinf of Oseltamivir and Oseltamivir Carboxylate for 30 mg Dose [ Time Frame: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose ] [ Designated as safety issue: No ]
    AUCinf is defined as the area under the plasma concentration-time curve from time zero extrapolated to infinity. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.

  • Cmax of Oseltamivir and Oseltamivir Carboxylate [ Time Frame: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose ] [ Designated as safety issue: No ]
    The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.

  • C120h, C168h and Clast of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose [ Time Frame: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose ] [ Designated as safety issue: No ]

    C120h is defined as the plasma concentration at 120 hours post-dose. C168h is defined as the plasma concentration at 168 hours post-dose. Clast is defined as the plasma concentration corresponding to the time of the last measureable (positive) plasma concentration.

    Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.


  • Tmax and T1/2 of Oseltamivir and Oseltamivir Carboxylate [ Time Frame: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose ] [ Designated as safety issue: No ]

    The Time of observed maximum plasma concentration (Tmax) is defined as actual sampling time to reach maximum observed analyte concentration.

    The Elimination Half-Life Period (T1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.


  • Renal Clearance (CLR) of Oseltamivir and Oseltamivir Carboxylate [ Time Frame: Pre-dose; 0.5, 1.33, 2, 2.5, 3, 4, 5, 6.67, 8, 10, 12, 14, 16, 20, 24, 28, 32, 48, 72, 96, 120, 144, and 168 hrs post-dose for blood; pre-dose and 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hrs post-dose for urine. ] [ Designated as safety issue: No ]
    CLR is calculated as the cumulative amount of drug excreted into urine from 0 to time t hours (Ae0-tlast) / area under the concentration-time curve from time zero through the last quantifiable concentration time (AUC0-t).


Secondary Outcome Measures:
  • Number of Participants With Any Adverse Event (AEs) and Any Serious Adverse Events (SAEs) [ Time Frame: Approximately 7 weeks ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the intervention. 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 Marked Abnormality in Laboratory Measurements [ Time Frame: Approximately 7 weeks ] [ Designated as safety issue: No ]

    Laboratory analysis included: hematology (hemoglobin, hematocrit, reticulocyte, red blood cell, platelet and white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin), prothrombin and activated partial thromboplastin time, biochemistry (sodium, potassium, bicarbonate, phosphate, chloride, calcium, urea, serum creatinine, bilirubin, cholesterol, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase [ALT], gamma-glutamyl transferase, protein, albumin, amylase, creatinine, lipase), random glucose, and urinalysis.

    Laboratory test result values falling outside of the marked abnormality range that also represent a defined change from baseline were considered as marked laboratory abnormalities. A marked reference range for sodium is 130-150 millimole (mmol)/L, chloride is 95-115 mmol/L, phosphate is 0.75-1.60 mmol/L, calcium is 2-2.90 mmol/L, glucose is 2.8-11.10 mmol/L, bicarbonate is 18-28 mmol/L, and ALT is 0-110 Unit/L.


  • Number of Participants With Change From Baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters at Follow-up Visit [ Time Frame: From Baseline (Day -1) to Follow-up visit (Days 15 to 22) ] [ Designated as safety issue: No ]
    ECG parameter included QT interval, QTcB interval and QTcF interval (all intervals are measured in millisecond [msec]). Marked abnormality in ECG is predefined for QT, QTcB, and QTcF interval as <=30, >30-60, and >60 msec increase from baseline.

  • Number of Participants With Abnormal Shifts in Vital Signs [ Time Frame: Days 1 (post-dose), 2, 3, 4, 5, 6, 7, 8; and Follow-up visit (Days 15 to 22) ] [ Designated as safety issue: No ]

    Vital signs included pulse rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body temperature.

    Vital sign with abnormal shifts from normal at baseline to high or low at post-baseline time points were recorded. Blood pressure was recorded in millimeter of mercury (mmHg), and temperature in degrees Celsius. Low blood pressure defined as <=70 mmHg (SBP) and <=40 mmHg (DBP); high blood pressure defined as >=140 mmHg (SBP) and >=90 mmHg (DBP); low temperature defined as <=36.5 degrees Celsius and high temperature defined as >=37.5 degrees Celsius.



Enrollment: 16
Study Start Date: March 2012
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Volunteers on dialysis Drug: Tamiflu (oseltamivir)
Single dose of Tamiflu in volunteers on dialysis
Experimental: Volunteers with reduced creatinine clearance Drug: Tamiflu (oseltamivir)
Single dose of Tamiflu in volunteers with creatinine clearance from 10 to 30 mL/min

  Eligibility

Ages Eligible for Study:   19 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

General

  • Adult volunteers, aged 19 to 90 years
  • Medically stable with no hospitalization for a significant disease in the 3 months before study start

Volunteers on dialysis

  • A documented and well-established dialysis therapy

Volunteers with reduced creatinine clearance

  • Creatinine clearance from 10 to 30 mL/min
  • Stable renal function

Exclusion Criteria:

  • Clinically significant and unstable disease (e.g., cardiac, hepatic, pulmonary)
  • Medical history of concurrent medical condition that would compromise participation in the study
  • Hypotensive episodes or symptoms of fainting, dizziness or lightheadedness in the 4 weeks before screening
  • Uncontrolled hypotension or hypertension
  • Infection with hepatitis B, hepatitis C or human immunodeficiency virus
  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: NCT01556633

Locations
New Zealand
Christchurch, New Zealand, 8011
Grafton, New Zealand, 1010
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01556633     History of Changes
Other Study ID Numbers: NV25655 
Study First Received: March 15, 2012
Results First Received: November 30, 2015
Last Updated: May 26, 2016
Health Authority: New Zealand: Ministry of Health

Additional relevant MeSH terms:
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 24, 2016