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This open-label, randomized, cross-over study evaluated the effect of tocilizumab (TCZ) on the pharmacokinetics and pharmacodynamics of a common oral contraceptive (OC) in female patients with active rheumatoid arthritis (RA) and in healthy female volunteers of child bearing age. The RA patients received OC in combination with TCZ, whereas the healthy volunteers received OC only. The RA patients received OC in 3 cycles of 21 days each; TCZ 8 mg/kg was administered once as an intravenous infusion on the first day of Cycle 2. The healthy volunteers received OC for only one 21-day cycle.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1) | Experimental | Patients with rheumatoid arthritis received Ortho-Novum® 1/35 daily on Days 1-21 of 3 consecutive 28-day cycles. On the first day of Cycle 2, patients received tocilizumab 8 mg/kg administered intravenously. |
|
| Ortho-Novum® 1/35 (Group 2) | Other | Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tocilizumab | Drug | Tocilizumab 8 mg/kg was administered in a single 1-hour infusion on Day 1 of Cycle 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Serum Progesterone Level | Blood samples were collected prior to the administration of Ortho-Novum® 1/35 on Day 21 of each cycle. Serum levels of progesterone were quantitatively determined using the ADVIA Centaur and ADVIA Centaur XP systems (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA). The assay was a competitive immunoassay using direct chemiluminescent technology. | Day 21 of Cycles 1-3 for Group 1 and Day 21 of Cycle 1 for Group 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The maximum observed plasma concentration (Cmax) was derived from the plasma concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). |
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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 | 72212 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24161161 | Derived | Zhang X, Rowell L, Fettner S, Lau C, Teuber D. Assessment of disease-drug-drug interaction between single-dose tocilizumab and oral contraceptives in women with active rheumatoid arthritis. Int J Clin Pharmacol Ther. 2014 Jan;52(1):27-38. doi: 10.5414/CP201951. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1) | Patients with rheumatoid arthritis received Ortho-Novum® 1/35 daily on Days 1-21 of 3 consecutive 28-day cycles. On the first day of Cycle 2, patients received tocilizumab 8 mg/kg administered intravenously. |
| FG001 | Ortho-Novum® 1/35 (Group 2) | Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1) | Patients with rheumatoid arthritis received Ortho-Novum® 1/35 daily on Days 1-21 of 3 consecutive 28-day cycles. On the first day of Cycle 2, patients received tocilizumab 8 mg/kg administered intravenously. |
| BG001 | Ortho-Novum® 1/35 (Group 2) |
| 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 | Serum Progesterone Level | Blood samples were collected prior to the administration of Ortho-Novum® 1/35 on Day 21 of each cycle. Serum levels of progesterone were quantitatively determined using the ADVIA Centaur and ADVIA Centaur XP systems (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA). The assay was a competitive immunoassay using direct chemiluminescent technology. | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. Blood samples were not available for all patients at all time points. | Posted | Mean | Standard Deviation | ng/mL | Day 21 of Cycles 1-3 for Group 1 and Day 21 of Cycle 1 for Group 2 |
|
Adverse events were reported from the date of signing informed consent through the follow-up visit.
The safety analysis population included all subjects who received at least 1 study dose and had at least 1 post-dose safety assessment.
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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 | Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1) | Patients with rheumatoid arthritis received Ortho-Novum® 1/35 daily on Days 1-21 of 3 consecutive 28-day cycles. On the first day of Cycle 2, patients received tocilizumab 8 mg/kg administered intravenously. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypersensitivity | Immune system disorders | MedDRA (14.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 |
Not provided
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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| Ortho-Novum® 1/35 | Drug | Each Ortho-Novum® 1/35 tablet contained 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. |
|
| Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
| Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The time to reach the maximum plasma concentration (Tmax) was derived from the plasma concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
| Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) was derived from the plasma concentrations using a non-compartmental method and computed using the linear trapezoidal rule with the software WinNonlin Enterprise version 5.2 (or above). | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
| Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The terminal half-life (t½) was derived from the plasma concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
| Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The apparent oral clearance (CL/F) was derived from the plasma concentrations using a non-compartmental method and computed as dose/AUC0-24 with the software WinNonlin Enterprise version 5.2 (or above). | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
| Maximum Observed Serum Concentration (Cmax) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated enzyme-linked immunosorbent assay (ELISA). The maximum observed plasma concentration (Cmax) was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Time to Reach Maximum Serum Concentration (Tmax) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The time to reach maximum serum concentration was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Area Under the Serum Concentration-time Curve From 0 to Infinity (AUCinf) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The area under the serum concentration-time curve from 0 to infinity (AUCinf) was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). AUCinf was computed using the linear trapezoidal rule to tlast plus Clast/Kel, where tlast is the time of the last measurable concentration, Clast is the last measurable concentration, and Kel is the apparent elimination rate, computed as the magnitude of the slope from the log-linear regression of the apparent terminal elimination phase of the serum concentration-versus-time curve. | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Terminal Half-life (t½) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The terminal half-life (t½) was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Clearance (CL) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. Clearance (CL), computed as dose/AUCinf, was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Apparent Volume of Distribution (Vz) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The apparent volume of distribution (Vz), computed as CL/Kel where CL is clearance and Kel is the apparent elimination rate, was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Serum Soluble Interleukin-6 Receptor (sIL-6R) Level | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, and 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. Serum levels of soluble interleukin-6 receptor were analyzed using a validated ELISA. | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Serum C-reactive Protein (CRP) Level | Blood samples were collected pre-dose of tocilizumab infusion on Day 1 of Cycle 2 and on Days 2, 3, 5, 7, 12, 14, and 21 of Cycle 2, and on Days 1, 7, and 21 of Cycle 3. Serum levels of C-reactive protein were measured by the Tina-quant CRP (latex) high-sensitivity Roche Immunoturbidimetric method. | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
| Beverly Hills |
| California |
| 90211 |
| United States |
| Ormond Beach | Florida | 32174 | United States |
| Port Orange | Florida | 32127 | United States |
| Duncansville | Pennsylvania | 16635 | United States |
| San Antonio | Texas | 78222 | United States |
| Other |
|
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Ortho-Novum® 1/35 (Group 2) | Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle. |
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The maximum observed plasma concentration (Cmax) was derived from the plasma concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. Blood samples were not available for all patients at all time points. | Posted | Mean | Standard Deviation | pg/mL | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
|
|
|
| Secondary | Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The time to reach the maximum plasma concentration (Tmax) was derived from the plasma concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | hr | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
|
|
|
| Secondary | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) was derived from the plasma concentrations using a non-compartmental method and computed using the linear trapezoidal rule with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | pg•hr/mL | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
|
|
|
| Secondary | Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The terminal half-life (t½) was derived from the plasma concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | hr | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
|
|
|
| Secondary | Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone | Blood samples were collected prior to and at 0.5, 1, 1.5, 2, 3, 5, 8, 12 and 24 hours after administration of Ortho-Novum® 1/35 on Day 7 of each cycle. The concentrations of ethinyl estradiol and norethindrone were determined in human heparinized plasma according to a validated gas chromatography coupled to mass spectrometry (GC-MS) method. The apparent oral clearance (CL/F) was derived from the plasma concentrations using a non-compartmental method and computed as dose/AUC0-24 with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | mL/hr | Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2 |
|
|
|
| Secondary | Maximum Observed Serum Concentration (Cmax) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated enzyme-linked immunosorbent assay (ELISA). The maximum observed plasma concentration (Cmax) was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | µg/mL | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Time to Reach Maximum Serum Concentration (Tmax) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The time to reach maximum serum concentration was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | hr | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Area Under the Serum Concentration-time Curve From 0 to Infinity (AUCinf) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The area under the serum concentration-time curve from 0 to infinity (AUCinf) was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). AUCinf was computed using the linear trapezoidal rule to tlast plus Clast/Kel, where tlast is the time of the last measurable concentration, Clast is the last measurable concentration, and Kel is the apparent elimination rate, computed as the magnitude of the slope from the log-linear regression of the apparent terminal elimination phase of the serum concentration-versus-time curve. | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | µg•hr/mL | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Terminal Half-life (t½) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The terminal half-life (t½) was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | hr | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Clearance (CL) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. Clearance (CL), computed as dose/AUCinf, was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | mL/hr | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Apparent Volume of Distribution (Vz) of Tocilizumab | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. The concentration of tocilizumab was determined in serum samples using a validated ELISA. The apparent volume of distribution (Vz), computed as CL/Kel where CL is clearance and Kel is the apparent elimination rate, was derived from the serum concentrations using a non-compartmental method with the software WinNonlin Enterprise version 5.2 (or above). | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | L | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Serum Soluble Interleukin-6 Receptor (sIL-6R) Level | Blood samples were collected pre-dose and at the end of infusion of tocilizumab on Day 1 of Cycle 2. Additional blood samples were collected on Days 2, 3, 5, 7, 12, 14, and 21 of Cycle 2, and Days 1, 7, and 21 of Cycle 3. Serum levels of soluble interleukin-6 receptor were analyzed using a validated ELISA. | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | ng/mL | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| Secondary | Serum C-reactive Protein (CRP) Level | Blood samples were collected pre-dose of tocilizumab infusion on Day 1 of Cycle 2 and on Days 2, 3, 5, 7, 12, 14, and 21 of Cycle 2, and on Days 1, 7, and 21 of Cycle 3. Serum levels of C-reactive protein were measured by the Tina-quant CRP (latex) high-sensitivity Roche Immunoturbidimetric method. | Pharmacokinetic (PK) and pharmacodynamic (PD) population: All patients enrolled in the study who had at least 1 evaluable PK or PD sample reading. | Posted | Mean | Standard Deviation | mg/L | From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1 |
|
|
|
| 1 |
| 23 |
| 12 |
| 23 |
| EG001 | Ortho-Novum® 1/35 (Group 2) | Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle. | 0 | 23 | 4 | 23 |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| LFT abnormal | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Systolic hypertension | Vascular disorders | MedDRA (14.1) | 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.
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Cycle 3, ethinyl estradiol, N=18,NA |
|
| Cycle 1, norethindrone, N=22,21 |
|
| Cycle 2, norethindrone, N=18,NA |
|
| Cycle 3, norethindrone, N=18,NA |
|
| Cycle 3, ethinyl estradiol |
|
| Cycle 1, norethindrone |
|
| Cycle 2, norethindrone |
|
| Cycle 3, norethindrone |
|
| Cycle 3, ethinyl estradiol |
|
| Cycle 1, norethindrone |
|
| Cycle 2, norethindrone |
|
| Cycle 3, norethindrone |
|
| Cycle 3, ethinyl estradiol |
|
| Cycle 1, norethindrone |
|
| Cycle 2, norethindrone |
|
| Cycle 3, norethindrone |
|
| Cycle 3, ethinyl estradiol |
|
| Cycle 1, norethindrone |
|
| Cycle 2, norethindrone |
|
| Cycle 3, norethindrone |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 5 |
|
| Cycle 2, Day 7 |
|
| Cycle 2, Day 12 |
|
| Cycle 2, Day 14 |
|
| Cycle 2, Day 21 |
|
| Cycle 3, Day 1 |
|
| Cycle 3, Day 7 |
|
| Cycle 3, Day 21 |
|
| Title | Measurements |
|---|---|
|
| Cycle 2, Day 5 |
|
| Cycle 2, Day 7 |
|
| Cycle 2, Day 12 |
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| Cycle 2, Day 14 |
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| Cycle 2, Day 21 |
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| Cycle 3, Day 1 |
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| Cycle 3, Day 7 |
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| Cycle 3, Day 21 |
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