Clinical trial NCT01556633: A Single Dose Study of Tamiflu in Volunteers in Dialysis And in Volunteers With Reduced Creatinine Clearance
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-03-16
Enrollment: 16
Sex: ALL
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Total Dialysate Clearance for Automated Peritoneal Dialysis (CLDAPD) of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose
timeFrame: 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
measure: AUC120, AUC168 and AUCinf of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose
timeFrame: 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
measure: AUCinf of Oseltamivir and Oseltamivir Carboxylate for 30 mg Dose
timeFrame: 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
measure: Cmax of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: C120h, C168h and Clast of Oseltamivir and Oseltamivir Carboxylate for 75 mg Dose
timeFrame: 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
measure: Tmax and T1/2 of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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
measure: Renal Clearance (CLR) of Oseltamivir and Oseltamivir Carboxylate
timeFrame: 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 outcomes:
measure: Number of Participants With Any Adverse Event (AEs) and Any Serious Adverse Events (SAEs)
timeFrame: Approximately 7 weeks
measure: Number of Participants With Marked Abnormality in Laboratory Measurements
timeFrame: Approximately 7 weeks
measure: Number of Participants With Change From Baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters at Follow-up Visit
timeFrame: From Baseline (Day -1) to Follow-up visit (Days 15 to 22)
measure: Number of Participants With Abnormal Shifts in Vital Signs
timeFrame: Days 1 (post-dose), 2, 3, 4, 5, 6, 7, 8; and Follow-up visit (Days 15 to 22)
Other outcomes:
Locations:
city: Christchurch
country: New Zealand
city: Grafton
country: New Zealand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Patel K, Rayner CR, Giraudon M, Kamal MA, Morcos PN, Robson R, Kirkpatrick CM. Pharmacokinetics and safety of oseltamivir in patients with end-stage renal disease treated with automated peritoneal dialysis. Br J Clin Pharmacol. 2015 Apr;79(4):624-35. doi: 10.1111/bcp.12526.