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

NCT01556633 | Completed Phase 1 Results

• 1 other identifier: NV25655
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (7)

• 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

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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).

  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 (4)

• Number of Participants With Any Adverse Event (AEs) and Any Serious Adverse Events (SAEs)

  Approximately 7 weeks

• Number of Participants With Marked Abnormality in Laboratory Measurements

  Approximately 7 weeks

• Number of Participants With Change From Baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters at Follow-up Visit

  From Baseline (Day -1) to Follow-up visit (Days 15 to 22)

• Number of Participants With Abnormal Shifts in Vital Signs

  Days 1 (post-dose), 2, 3, 4, 5, 6, 7, 8; and Follow-up visit (Days 15 to 22)

Study Arms (2)

Volunteers on dialysis

EXPERIMENTAL

Drug: Tamiflu (oseltamivir)

Volunteers with reduced creatinine clearance

EXPERIMENTAL

Drug: Tamiflu (oseltamivir)

Interventions

Tamiflu (oseltamivir) DRUG

Single dose of Tamiflu in volunteers on dialysis

Volunteers on dialysis

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Unknown Facility

Christchurch, 8011, New Zealand

Location

Unknown Facility

Grafton, 1010, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 25289522 DERIVED

MeSH Terms

Interventions

Oseltamivir

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 616878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: March 16, 2012
• Study Start: March 1, 2012
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 7, 2016
• Results First Posted: July 7, 2016

Record last verified: 2016-05

Locations

NZ (2)