Trial Outcomes & Findings for A Pharmacokinetic Study on Co-administration of Tamiflu (Oseltamivir) and Rimantadine in Healthy Volunteers (NCT NCT01172847)
NCT ID: NCT01172847
Last Updated: 2016-08-19
Results Overview
Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 of oseltamivir and oseltamivir carboxylate were calculated following the administration of oseltamivir alone or in combination with rimantadine, using the linear trapezoidal rule.
COMPLETED
PHASE1
24 participants
Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5
2016-08-19
Participant Flow
This study was conducted at a single center in the United States from 04 August 2009 to 28 September 2009. A total of 40 participants were screened.
Of 40 participants, 24 participants were enrolled.
Participant milestones
| Measure |
Oseltamivir; Rimantadine; Oseltamivir + Rimantadine
Participants received treatments in 3 periods as: Oseltamivir 75 milligram \[mg\] (twice a day orally for 5 days), Rimantadine 100 mg (twice a day orally for 5 days), and Oseltamivir 75 mg + Rimantadine 100 mg (twice a day orally for 5 days) in a randomly determined sequence with a minimum 7-day wash out period between consecutive treatments periods.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
Oseltamivir
|
24
|
|
Overall Study
Rimantadine
|
22
|
|
Overall Study
Oseltamivir + Rimantadine
|
21
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Oseltamivir; Rimantadine; Oseltamivir + Rimantadine
Participants received treatments in 3 periods as: Oseltamivir 75 milligram \[mg\] (twice a day orally for 5 days), Rimantadine 100 mg (twice a day orally for 5 days), and Oseltamivir 75 mg + Rimantadine 100 mg (twice a day orally for 5 days) in a randomly determined sequence with a minimum 7-day wash out period between consecutive treatments periods.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
A Pharmacokinetic Study on Co-administration of Tamiflu (Oseltamivir) and Rimantadine in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Oseltamivir; Rimantadine; Oseltamivir + Rimantadine
n=24 Participants
Participants received treatments in 3 periods as: Oseltamivir 75 milligram \[mg\] (twice a day orally for 5 days), Rimantadine 100 mg (twice a day orally for 5 days), and Oseltamivir 75 mg + Rimantadine 100 mg (twice a day orally for 5 days) in a randomly determined sequence with a minimum 7-day wash out period between consecutive treatments periods.
|
|---|---|
|
Age, Continuous
|
33.5 years
STANDARD_DEVIATION 7.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5Population: Pharmacokinetics (PK) analysis population included all participants who were adhered to the protocol.
Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 of oseltamivir and oseltamivir carboxylate were calculated following the administration of oseltamivir alone or in combination with rimantadine, using the linear trapezoidal rule.
Outcome measures
| Measure |
Oseltamivir
n=21 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir
|
5.092 hours (h)*nanogram (ng)/milliliter (mL)
Interval 5.041 to 5.143
|
5.070 hours (h)*nanogram (ng)/milliliter (mL)
Interval 5.019 to 5.121
|
—
|
|
Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate
|
8.008 hours (h)*nanogram (ng)/milliliter (mL)
Interval 7.982 to 8.034
|
7.990 hours (h)*nanogram (ng)/milliliter (mL)
Interval 7.964 to 8.017
|
—
|
PRIMARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5Population: Pharmacokinetic analysis population included all participants who were adhered to the protocol.
AUC0-12 of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir, using the linear trapezoidal rule.
Outcome measures
| Measure |
Oseltamivir
n=21 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Rimantadine
|
8.371 h*ng/mL
Interval 8.349 to 8.394
|
8.398 h*ng/mL
Interval 8.376 to 8.421
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5Population: PK analysis population included all participants who were adhered to the protocol.
Oseltamivir carboxylate is active metabolite of oseltamivir. Cmax of oseltamivir and oseltamivir carboxylate were calculated following the administration of oseltamivir alone or in combination with rimantadine and was directly observed from the data.
Outcome measures
| Measure |
Oseltamivir
n=21 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir
|
4.395 ng/mL
Interval 4.317 to 4.472
|
4.249 ng/mL
Interval 4.171 to 4.326
|
—
|
|
Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate
|
5.940 ng/mL
Interval 5.894 to 5.986
|
5.921 ng/mL
Interval 5.874 to 5.967
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5Population: PK analysis population included all participants who were adhered to the protocol.
Cmax of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir and was directly observed from the data.
Outcome measures
| Measure |
Oseltamivir
n=21 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Rimantadine
|
6.036 ng/mL
Interval 6.01 to 6.061
|
6.062 ng/mL
Interval 6.036 to 6.087
|
—
|
SECONDARY outcome
Timeframe: Up to 11 weeksPopulation: Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. 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.
Outcome measures
| Measure |
Oseltamivir
n=24 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=22 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
|
8 participants
|
6 participants
|
4 participants
|
SECONDARY outcome
Timeframe: Screening (Days -28 to -2); pre-dose and 2h post-dose on D1 and D5 of each treatment period; at Follow-up visit (10 -14 days after last dose) for blood pressure and HR; Screening; Day -1 of each treatment period; Follow-up visit for temperaturePopulation: Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
Vital signs included heart rate (HR), blood pressure (systolic blood pressure \[SBP\] and diastolic blood pressure \[DBP\]), and body temperature. Blood pressure and pulse rate were recorded when participants were rested in a supine position for at least 5 minutes and after standing for 2 minutes. Vital signs values that fall outside the investigator's normal ranges were recorded.
Outcome measures
| Measure |
Oseltamivir
n=24 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=22 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs
High- DBP
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Vital Signs
High- SBP
|
6 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Abnormal Vital Signs
High- DBP standing
|
8 participants
|
6 participants
|
2 participants
|
|
Number of Participants With Abnormal Vital Signs
High- SBP standing
|
7 participants
|
4 participants
|
3 participants
|
|
Number of Participants With Abnormal Vital Signs
High- HR
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Vital Signs
High- HR standing
|
2 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Abnormal Vital Signs
Low- Temperature
|
7 participants
|
11 participants
|
8 participants
|
SECONDARY outcome
Timeframe: Screening; Day -1 and Day 5 (pre-dose) of each treatment period; Follow-up visitPopulation: Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
Laboratory analysis included hematology (hemoglobin, hematocrit, erythrocytes, platelets counts, leukocytes counts, neutrophils, eosinophils, lymphocytes, basophils, and monocytes);, biochemistry (aspartate aminotransferase , alanine aminotransferase, gamma glutamyl trans peptidase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, albumin, creatinine, urea, creatine phosphokinase, total protein, sodium, chloride, calcium, phosphate, potassium, glucose (fasting), amylase, lipase, total cholesterol, and calculated creatinine clearance); and urinalysis. Marked laboratory test values (high and low) falling outside the marked reference range and which also represents a clinically relevant change from baseline of at least a designated amount were recoded. In this study, marked abnormality ranges for phosphate as 0.75 - 1.60 millimole (mmol)/L and proteinuria (0 to 4+, and 1).
Outcome measures
| Measure |
Oseltamivir
n=24 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=22 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Number of Participants With Marked Abnormality in Laboratory Parameters
Phosphate High
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Marked Abnormality in Laboratory Parameters
Phosphate Low
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Abnormality in Laboratory Parameters
Proteinuria
|
1 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Screening; pre-dose on Day 1 and Day 5 of each treatment period; Follow-up visitPopulation: Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
ECG was recorded when participants were rested in a supine position for at least 5 minutes.
Outcome measures
| Measure |
Oseltamivir
n=24 Participants
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=22 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 Participants
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant or Treatment Related Changes in Electrocardiogram (ECG)
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Oseltamivir
Rimantadine
Oseltamivir + Rimantadine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Oseltamivir
n=24 participants at risk
Participants received oseltamivir 75 mg twice a day orally for 5 days.
|
Rimantadine
n=22 participants at risk
Participants received rimantadine 100 mg twice a day orally for 5 days.
|
Oseltamivir + Rimantadine
n=21 participants at risk
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days.
|
|---|---|---|---|
|
Gastrointestinal disorders
Toothache
|
4.2%
1/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.5%
1/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.8%
1/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Gastrointestinal disorders
Nausea
|
4.2%
1/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.5%
1/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.5%
1/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.8%
1/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.5%
1/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Gastrointestinal disorders
Dry mouth
|
4.2%
1/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Nervous system disorders
Headache
|
12.5%
3/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.5%
1/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
9.1%
2/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.8%
1/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Nervous system disorders
Psychomotor hyperactivity
|
4.2%
1/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Cardiac disorders
Tachycardia
|
4.2%
1/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/24 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
0.00%
0/22 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
4.8%
1/21 • Up to 11 weeks
SAEs and other AEs were collected in the safety population which included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not.
|
Additional Information
Roche Trial Information Hotline
F. Hoffmann-La Roche AG
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER