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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01556633




Registration number
NCT01556633
Ethics application status
Date submitted
15/03/2012
Date registered
16/03/2012
Date last updated
7/07/2016

Titles & IDs
Public title
A Single Dose Study of Tamiflu in Volunteers in Dialysis And in Volunteers With Reduced Creatinine Clearance
Scientific 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
Secondary ID [1] 0 0
NV25655
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Volunteer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tamiflu (oseltamivir)
Treatment: Drugs - Tamiflu (oseltamivir)

Experimental: Volunteers on dialysis -

Experimental: Volunteers with reduced creatinine clearance -


Treatment: Drugs: Tamiflu (oseltamivir)
Single dose of Tamiflu in volunteers on dialysis

Treatment: Drugs: Tamiflu (oseltamivir)
Single dose of Tamiflu in volunteers with creatinine clearance from 10 to 30 mL/min

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Total Dialysate Clearance for Automated Peritoneal Dialysis (CLDAPD) of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose - 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
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
AUC120, AUC168 and AUCinf of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose - 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.
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
AUCinf of Oseltamivir and Oseltamivir Carboxylate for 30 mg Dose - 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.
Timepoint [3] 0 0
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
Primary outcome [4] 0 0
Cmax of Oseltamivir and Oseltamivir Carboxylate - The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Oseltamivir carboxylate is a clinically active metabolite of oseltamivir.
Timepoint [4] 0 0
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
Primary outcome [5] 0 0
C120h, C168h and Clast of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose - 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.
Timepoint [5] 0 0
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
Primary outcome [6] 0 0
Tmax and T1/2 of Oseltamivir and Oseltamivir Carboxylate - 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.
Timepoint [6] 0 0
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
Primary outcome [7] 0 0
Renal Clearance (CLR) of Oseltamivir and Oseltamivir Carboxylate - 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).
Timepoint [7] 0 0
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.
Secondary outcome [1] 0 0
Number of Participants With Any Adverse Event (AEs) and Any Serious Adverse Events (SAEs) - 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.
Timepoint [1] 0 0
Approximately 7 weeks
Secondary outcome [2] 0 0
Number of Participants With Marked Abnormality in Laboratory Measurements - 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.
Timepoint [2] 0 0
Approximately 7 weeks
Secondary outcome [3] 0 0
Number of Participants With Change From Baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters at Follow-up Visit - 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.
Timepoint [3] 0 0
From Baseline (Day -1) to Follow-up visit (Days 15 to 22)
Secondary outcome [4] 0 0
Number of Participants With Abnormal Shifts in Vital Signs - 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.
Timepoint [4] 0 0
Days 1 (post-dose), 2, 3, 4, 5, 6, 7, 8; and Follow-up visit (Days 15 to 22)

Eligibility
Key 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
Minimum age
19 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch
Country [2] 0 0
New Zealand
State/province [2] 0 0
Grafton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01556633
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications