Phase 3
N=215
A Study of Oseltamivir (Tamiflu) for Treatment of Influenza in Immunocompromised Participants.
Influenza, Human
Bottom Line
View on ClinicalTrials.gov: NCT00545532 ↗Enrolled (actual)
215
Serious AEs
8.4%
Results posted
Jul 2018
Primary outcome: Primary: Percentage of Participants With Adverse Events — 40.0; 47.3; 25.7; 29.1 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- oseltamivir (Drug); placebo (Other)
- Age
- Pediatric, Adult, Older Adult · 1+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- May 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Adverse Events |
40.0; 47.3; 25.7; 29.1 | — |
| PRIMARY Percentage of Participants Who Developed Viral Resistance to Oseltamivir |
8.2; 1.3; 9.6; 2.6; 25.0; 0 | — |
| PRIMARY Percentage of Participants With Tissue Rejection or Graft Versus Host Disease (GVHD) |
0; 0 | — |
| SECONDARY Time to Resolution (TTR) of All Clinical Influenza Symptoms |
103.3; 103.6; 103.4; 107.2; 32.1; 115.9 | — |
| SECONDARY Total Symptom Score Area Under the Efficacy Curve (AUE) |
774.7; 811.5 | — |
| SECONDARY Time to Resolution of Fever |
11.0; 0.5; 11.0; 0.5; NA; 26.0 | — |
| SECONDARY Change From Baseline in Viral Load Assessed by Culture |
3.38; 3.75; -1.50; -1.50; -2.50; -3.00 | — |
| SECONDARY Percentage of Participants With Viral Shedding Assessed by Culture Over Time |
91.4; 84.2; 67.2; 58.9; 15.4; 18.3 | — |
| SECONDARY Time to Cessation of Viral Shedding by Cell Culture |
105.0; 105.4; 150.3; 94.9 | — |
| SECONDARY Change From Baseline in Viral Load Assessed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) |
6.47; 6.52; -1.20; -1.35; -2.36; -2.34 | — |
| SECONDARY Percentage of Participants With Viral Shedding Assessed by RT-PCR Over Time |
100.0; 97.4; 92.8; 88.0; 56.7; 49.3 | — |
| SECONDARY Time to Cessation of Viral Shedding by RT-PCR |
178.0; 154.1; 181.0; 180.5 | — |
| SECONDARY Percentage of Participants With Persistent Viral Shedding |
1.2; 4.7 | — |
| SECONDARY Percentage of Participants Who Developed Secondary Illness |
8.2; 5.1; 12.5; 0.0 | — |
| SECONDARY Percentage of Participants Who Initiated Antibiotic Treatment |
8.2; 5.0; 14.3; 0.0 | — |
| SECONDARY Percentage of Participants Hospitalized |
6.8; 7.7; 11.1; 0.0 | — |
| SECONDARY Duration of Hospitalization |
7.0; 6.50; 5.0; NA | — |
| SECONDARY Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Oseltamivir in Adults |
65.5; 149 | — |
| SECONDARY Pharmacokinetics: Trough Plasma Concentration (Ctrough) of Oseltamivir in Adults |
2.33; 6.98 | — |
| SECONDARY Pharmacokinetics : Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC0-12) at Steady State of Oseltamivir in Adults |
197; 501 | — |
| SECONDARY Pharmacokinetics: Time to Maximum Concentration (Tmax) of Oseltamivir in Adults |
1.08; 1.08 | — |
| SECONDARY Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adults |
5.15; 4.79 | — |
| SECONDARY Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adults |
402; 367 | — |
| SECONDARY Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adults |
77.5; 75.4 | — |
| SECONDARY Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adults |
655; 1420 | — |
| SECONDARY Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adults |
363; 831 | — |
| SECONDARY Pharmacokinetics : AUC0-12 at Steady State of Oseltamivir Carboxylate in Adults |
6240; 13800 | — |
| SECONDARY Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adults |
3.83; 3.96 | — |
| SECONDARY Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adults |
1.67; 1.61 | — |
| SECONDARY Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir Carboxylate in Adults |
14.0; 13.5 | — |
| SECONDARY Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adults |
8.39; 8.39 | — |
| SECONDARY Pharmacokinetics: Cmax of Oseltamivir in Adolescents and Children |
61.9; 45.9; 107; 86.6 | — |
| SECONDARY Pharmacokinetics: Ctrough of Oseltamivir in Adolescents and Children |
2.84; 3.37; 6.65; 3.88 | — |
| SECONDARY Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir in Adolescents and Children |
229; 171; 425; 339 | — |
| SECONDARY Pharmacokinetics: Tmax of Oseltamivir in Adolescents and Children |
1; 1; 1; 1.25 | — |
| SECONDARY Pharmacokinetics: Cmax of Oseltamivir Carboxylate in Adolescents and Children |
363; 848; 770; 906 | — |
| SECONDARY Pharmacokinetics: Ctrough of Oseltamivir Carboxylate in Adolescents and Children |
215; 459; 445; 464 | — |
| SECONDARY Pharmacokinetics: AUC0-12 at Steady State of Oseltamivir Carboxylate in Adolescents and Children |
3550; 8010; 7460; 8420 | — |
| SECONDARY Pharmacokinetics: Tmax of Oseltamivir Carboxylate in Adolescents and Children |
3.75; 4; 4; 4 | — |
| SECONDARY Pharmacokinetics: Elimination Constant (ke) of Oseltamivir in Adolescents and Children |
4.22; 4.56; 3.40; 5.74 | — |
| SECONDARY Pharmacokinetics: Apparent Clearance (CL/F) of Oseltamivir in Adolescents and Children |
263; 439; 212; 442 | — |
| SECONDARY Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir in Adolescents and Children |
62.3; 96.4; 62.3; 76.9 | — |
| SECONDARY Pharmacokinetics: Elimination Constant (ke) of Oseltamivir Carboxylate in Adolescents and Children |
2.01; 1.12; 1.44; 2.12 | — |
| SECONDARY Pharmacokinetics: Apparent Clearance (CL/F), of Oseltamivir Carboxylate in Adolescents and Children |
16.9; 9.36; 12.1; 17.8 | — |
| SECONDARY Pharmacokinetics: Apparent Volume of Distribution (Vc/F) of Oseltamivir Carboxylate in Adolescents and Children |
8.39; 8.39; 8.39; 8.39 | — |
Summary
This 2-arm study will investigate the safety and tolerability of oseltamivir for the treatment of influenza in immunocompromised participants and characterize the effects of oseltamivir in immunocompromised participants on the development of resistant influenza virus. Eligible immunocompromised participants with laboratory-confirmed influenza will be randomized to receive either conventional dose (30 milligrams [mg] to 75 mg twice daily orally [po], depending on age and weight) or double dose (60 mg-150 mg twice daily po depending on age and weight) olseltamivir for 10 days. Nasal and throat swabs will be taken, and safety evaluations made, at intervals during the study. The anticipated time on study medication is 10 days and the anticipated time on study is 40 days.
Eligibility Criteria
Inclusion Criteria
- Rapid diagnostic test, PCR, or viral culture positive for influenza in the 96 hours prior to first dose
- Immunocompromised participants with primary or secondary immunodeficiency
- Symptoms suggestive of influenza-like illness
- Use of an effective contraceptive, as specified by protocol; women of childbearing potential cannot be pregnant or breastfeeding
Exclusion Criteria
- Influenza vaccination with live attenuated vaccine in the 2 weeks prior to randomization
- Antiviral treatment for influenza in 2 weeks prior to randomization
- Severe hepatic impairment
- Any current renal replacement therapy
- Any gastrointestinal disorders which may interfere with the absorption of oseltamivir
- Participation in a study with an investigational drug from 4 weeks prior to study start until study end
Data sourced from ClinicalTrials.gov (NCT00545532). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.