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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-012742-23 |
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This open label, randomized, three-period crossover study will evaluate the effect of co-administration of Tamiflu (oseltamivir) and rimantadine on the pharmacokinetics of Tamiflu and rimantadine. Healthy volunteers will receive multiple oral doses of Tamiflu, rimantadine or Tamiflu plus rimantadine in random order, with a minimum wash-out period of 7 days between treatments. Anticipated time on study is up to 11 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Active Comparator |
| |
| B | Active Comparator |
| |
| C | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oseltamivir [Tamiflu] | Drug | multiple oral doses |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 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. | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
| Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Rimantadine | AUC0-12 of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir, using the linear trapezoidal rule. | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate | 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. | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Little Rock | Arkansas | 72204 | United States |
Of 40 participants, 24 participants were enrolled.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 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. | Pharmacokinetics (PK) analysis population included all participants who were adhered to the protocol. | Posted | Least Squares Mean | 90% Confidence Interval | hours (h)*nanogram (ng)/milliliter (mL) | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oseltamivir | Participants received oseltamivir 75 mg twice a day orally for 5 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Toothache | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roche Trial Information Hotline | F. Hoffmann-La Roche AG | +41 61 6878333 | global.trial_information@roche.com |
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| ID | Term |
|---|---|
| D053139 | Oseltamivir |
| D012299 | Rimantadine |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D053138 | Cyclohexenes |
| D003510 |
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| rimantadine |
| Drug |
multiple oral doses |
|
| Maximum Plasma Concentration (Cmax) of Rimantadine | Cmax of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir and was directly observed from the data. | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
| Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | 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. | Up to 11 weeks |
| Number of Participants With Abnormal Vital Signs | 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. | 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 temperature |
| Number of Participants With Marked Abnormality in Laboratory Parameters | 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). | Screening; Day -1 and Day 5 (pre-dose) of each treatment period; Follow-up visit |
| Number of Participants With Clinically Significant or Treatment Related Changes in Electrocardiogram (ECG) | ECG was recorded when participants were rested in a supine position for at least 5 minutes. | Screening; pre-dose on Day 1 and Day 5 of each treatment period; Follow-up visit |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Oseltamivir + Rimantadine |
Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days. |
|
|
|
| Primary | Steady State Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours After Dosing (AUC0-12) of Rimantadine | AUC0-12 of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir, using the linear trapezoidal rule. | Pharmacokinetic analysis population included all participants who were adhered to the protocol. | Posted | Least Squares Mean | 90% Confidence Interval | h*ng/mL | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
|
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate | 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. | PK analysis population included all participants who were adhered to the protocol. | Posted | Least Squares Mean | 90% Confidence Interval | ng/mL | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
|
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of Rimantadine | Cmax of rimantadine was calculated following the administration of rimantadine alone or in combination with oseltamivir and was directly observed from the data. | PK analysis population included all participants who were adhered to the protocol. | Posted | Least Squares Mean | 90% Confidence Interval | ng/mL | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 5 |
|
|
|
|
| Secondary | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | 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. | Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not. | Posted | Number | participants | Up to 11 weeks |
|
|
|
| Secondary | Number of Participants With Abnormal Vital Signs | 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. | Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not. | Posted | Number | participants | 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 temperature |
|
|
|
| Secondary | Number of Participants With Marked Abnormality in Laboratory Parameters | 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). | Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not. | Posted | Number | participants | Screening; Day -1 and Day 5 (pre-dose) of each treatment period; Follow-up visit |
|
|
|
| Secondary | Number of Participants With Clinically Significant or Treatment Related Changes in Electrocardiogram (ECG) | ECG was recorded when participants were rested in a supine position for at least 5 minutes. | Safety Population included all participants who received at least one dose of the study medication, whether prematurely withdrawn from the study or not. | Posted | Number | participants | Screening; pre-dose on Day 1 and Day 5 of each treatment period; Follow-up visit |
|
|
|
| 0 |
| 24 |
| 8 |
| 24 |
| EG001 | Rimantadine | Participants received rimantadine 100 mg twice a day orally for 5 days. | 0 | 22 | 6 | 22 |
| EG002 | Oseltamivir + Rimantadine | Participants received oseltamivir 75 mg + rimantadine 100 mg twice a day orally for 5 days. | 0 | 21 | 4 | 21 |
| Nausea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Psychomotor hyperactivity | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 12.1 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
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.
| Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
Mean exposure ratio of oseltamivir carboxylate
| mean exposure ratio |
| 0.98 |
| 2-Sided |
| 90 |
| 0.92 |
| 1.05 |
Estimate of the treatment difference and corresponding 90% CI was derived from the back-transformed model. |
| No |
| Superiority or Other |
| Title | Measurements |
|---|---|
|
| High- DBP standing |
|
| High- SBP standing |
|
| High- HR |
|
| High- HR standing |
|
| Low- Temperature |
|
| Title | Measurements |
|---|---|
|
| Proteinuria |
|