Trial Outcomes & Findings for A Study of Tocilizumab in Combination With an Oral Contraceptive in Patients With Rheumatoid Arthritis (NCT NCT01044498)
NCT ID: NCT01044498
Last Updated: 2013-04-01
Results Overview
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.
COMPLETED
PHASE3
46 participants
Day 21 of Cycles 1-3 for Group 1 and Day 21 of Cycle 1 for Group 2
2013-04-01
Participant Flow
Participant milestones
| Measure |
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.
|
Ortho-Novum® 1/35 (Group 2)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
23
|
|
Overall Study
COMPLETED
|
20
|
21
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
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.
|
Ortho-Novum® 1/35 (Group 2)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Overall Study
Withdrew consent
|
1
|
1
|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
A Study of Tocilizumab in Combination With an Oral Contraceptive in Patients With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=23 Participants
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)
n=23 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
35.8 years
STANDARD_DEVIATION 7.66 • n=99 Participants
|
25.7 years
STANDARD_DEVIATION 5.04 • n=107 Participants
|
30.7 years
STANDARD_DEVIATION 8.22 • n=206 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 21 of Cycles 1-3 for Group 1 and Day 21 of Cycle 1 for Group 2Population: 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.
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.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=22 Participants
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)
n=16 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Serum Progesterone Level
Cycle 1 (n=22, 16)
|
0.21 ng/mL
Standard Deviation 0.07
|
0.57 ng/mL
Standard Deviation 0.39
|
|
Serum Progesterone Level
Cycle 2 (n=19, NA)
|
0.22 ng/mL
Standard Deviation 0.10
|
NA ng/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Serum Progesterone Level
Cycle 3 (n=18, NA)
|
0.19 ng/mL
Standard Deviation 0.00
|
NA ng/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
SECONDARY outcome
Timeframe: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2Population: 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.
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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=22 Participants
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)
n=21 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Cycle 1, ethinyl estradiol, N=22,21
|
183 pg/mL
Standard Deviation 86.2
|
157 pg/mL
Standard Deviation 53.3
|
|
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Cycle 2, ethinyl estradiol, N=18,NA
|
163 pg/mL
Standard Deviation 71.4
|
NA pg/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Cycle 3, ethinyl estradiol, N=18,NA
|
177 pg/mL
Standard Deviation 104.2
|
NA pg/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Cycle 1, norethindrone, N=22,21
|
13396 pg/mL
Standard Deviation 4687.9
|
18943 pg/mL
Standard Deviation 5570.6
|
|
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Cycle 2, norethindrone, N=18,NA
|
14747 pg/mL
Standard Deviation 4215.8
|
NA pg/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Cycle 3, norethindrone, N=18,NA
|
15772 pg/mL
Standard Deviation 4863.4
|
NA pg/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
SECONDARY outcome
Timeframe: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=22 Participants
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)
n=21 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
Cycle 1, ethinyl estradiol
|
1.42 hr
Standard Deviation 0.68
|
1.28 hr
Standard Deviation 0.54
|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
Cycle 2, ethinyl estradiol
|
1.90 hr
Standard Deviation 2.69
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
Cycle 3, ethinyl estradiol
|
1.58 hr
Standard Deviation 0.73
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
Cycle 1, norethindrone
|
1.33 hr
Standard Deviation 0.73
|
1.02 hr
Standard Deviation 0.47
|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
Cycle 2, norethindrone
|
1.82 hr
Standard Deviation 1.59
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Ethinyl Estradiol and Norethindrone
Cycle 3, norethindrone
|
1.30 hr
Standard Deviation 0.46
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
SECONDARY outcome
Timeframe: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=22 Participants
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)
n=21 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
Cycle 1, ethinyl estradiol
|
1387 pg•hr/mL
Standard Deviation 453
|
1389 pg•hr/mL
Standard Deviation 502
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
Cycle 2, ethinyl estradiol
|
1409 pg•hr/mL
Standard Deviation 552
|
NA pg•hr/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
Cycle 3, ethinyl estradiol
|
1455 pg•hr/mL
Standard Deviation 487
|
NA pg•hr/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
Cycle 1, norethindrone
|
108513 pg•hr/mL
Standard Deviation 39795
|
128975 pg•hr/mL
Standard Deviation 53276
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
Cycle 2, norethindrone
|
120505 pg•hr/mL
Standard Deviation 43285
|
NA pg•hr/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Ethinyl Estradiol and Norethindrone
Cycle 3, norethindrone
|
121667 pg•hr/mL
Standard Deviation 47828
|
NA pg•hr/mL
Standard Deviation NA
There was only 1 cycle for Group 2.
|
SECONDARY outcome
Timeframe: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=22 Participants
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)
n=21 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
Cycle 1, ethinyl estradiol
|
14.71 hr
Standard Deviation 9.10
|
17.05 hr
Standard Deviation 9.71
|
|
Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
Cycle 2, ethinyl estradiol
|
14.70 hr
Standard Deviation 7.47
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
Cycle 3, ethinyl estradiol
|
15.24 hr
Standard Deviation 6.78
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
Cycle 1, norethindrone
|
12.18 hr
Standard Deviation 4.49
|
11.54 hr
Standard Deviation 4.20
|
|
Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
Cycle 2, norethindrone
|
13.48 hr
Standard Deviation 3.69
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Terminal Half-life (t½) of Ethinyl Estradiol and Norethindrone
Cycle 3, norethindrone
|
16.14 hr
Standard Deviation 10.97
|
NA hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
SECONDARY outcome
Timeframe: Day 7 of Cycles 1-3 for Group 1 and Day 7 of Cycle 1 for Group 2Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=22 Participants
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)
n=21 Participants
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
Cycle 1, ethinyl estradiol
|
28.49 mL/hr
Standard Deviation 11.40
|
28.64 mL/hr
Standard Deviation 11.06
|
|
Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
Cycle 2, ethinyl estradiol
|
29.23 mL/hr
Standard Deviation 12.88
|
NA mL/hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
Cycle 3, ethinyl estradiol
|
26.86 mL/hr
Standard Deviation 9.38
|
NA mL/hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
Cycle 1, norethindrone
|
10.40 mL/hr
Standard Deviation 3.59
|
9.05 mL/hr
Standard Deviation 3.71
|
|
Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
Cycle 2, norethindrone
|
9.45 mL/hr
Standard Deviation 3.59
|
NA mL/hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
|
Apparent Oral Clearance (CL/F) of Ethinyl Estradiol and Norethindrone
Cycle 3, norethindrone
|
9.53 mL/hr
Standard Deviation 3.72
|
NA mL/hr
Standard Deviation NA
There was only 1 cycle for Group 2.
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=20 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Maximum Observed Serum Concentration (Cmax) of Tocilizumab
|
204 µg/mL
Standard Deviation 63.4
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=20 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Time to Reach Maximum Serum Concentration (Tmax) of Tocilizumab
|
4.41 hr
Standard Deviation 8.39
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=20 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Area Under the Serum Concentration-time Curve From 0 to Infinity (AUCinf) of Tocilizumab
|
35038 µg•hr/mL
Standard Deviation 8324
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=20 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Terminal Half-life (t½) of Tocilizumab
|
145.92 hr
Standard Deviation 57.69
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=20 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Clearance (CL) of Tocilizumab
|
17.51 mL/hr
Standard Deviation 4.59
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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).
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=20 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz) of Tocilizumab
|
3.60 L
Standard Deviation 1.37
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=21 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 1
|
38.5 ng/mL
Standard Deviation 10.3
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 2
|
100.6 ng/mL
Standard Deviation 23.7
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 3
|
162.5 ng/mL
Standard Deviation 52.8
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 5
|
249.1 ng/mL
Standard Deviation 68.2
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 7
|
312.9 ng/mL
Standard Deviation 63.6
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 12
|
425.1 ng/mL
Standard Deviation 78.0
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 14
|
476.2 ng/mL
Standard Deviation 89.1
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 2, Day 21
|
503.2 ng/mL
Standard Deviation 131.8
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 3, Day 1
|
534.9 ng/mL
Standard Deviation 169.4
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 3, Day 7
|
387.3 ng/mL
Standard Deviation 188.0
|
—
|
|
Serum Soluble Interleukin-6 Receptor (sIL-6R) Level
Cycle 3, Day 21
|
45.7 ng/mL
Standard Deviation 12.4
|
—
|
SECONDARY outcome
Timeframe: From Day 1 of Cycle 2 to Day 21 of Cycle 3 for Group 1Population: 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 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.
Outcome measures
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=21 Participants
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)
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 1
|
16.86 mg/L
Standard Deviation 21.55
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 2
|
12.76 mg/L
Standard Deviation 16.07
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 3
|
7.53 mg/L
Standard Deviation 12.61
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 5
|
4.62 mg/L
Standard Deviation 12.47
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 7
|
3.90 mg/L
Standard Deviation 12.42
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 12
|
3.95 mg/L
Standard Deviation 13.22
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 14
|
3.92 mg/L
Standard Deviation 13.03
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 2, Day 21
|
3.97 mg/L
Standard Deviation 12.95
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 3, Day 1
|
3.74 mg/L
Standard Deviation 11.96
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 3, Day 7
|
8.11 mg/L
Standard Deviation 13.62
|
—
|
|
Serum C-reactive Protein (CRP) Level
Cycle 3, Day 21
|
12.37 mg/L
Standard Deviation 9.42
|
—
|
Adverse Events
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
Ortho-Novum® 1/35 (Group 2)
Serious adverse events
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=23 participants at risk
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)
n=23 participants at risk
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Immune system disorders
Hypersensitivity
|
4.3%
1/23 • 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.
|
0.00%
0/23 • 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.
|
Other adverse events
| Measure |
Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1)
n=23 participants at risk
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)
n=23 participants at risk
Healthy volunteers received Ortho-Novum® 1/35 tablets daily on Days 1-21 of one 28-day cycle.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
8.7%
2/23 • 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.
|
0.00%
0/23 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
8.7%
2/23 • 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.
|
0.00%
0/23 • 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.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.7%
2/23 • 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.
|
0.00%
0/23 • 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.
|
|
Nervous system disorders
Headache
|
13.0%
3/23 • 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.
|
0.00%
0/23 • 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.
|
|
Investigations
LFT abnormal
|
8.7%
2/23 • 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.
|
0.00%
0/23 • 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.
|
|
Gastrointestinal disorders
Nausea
|
8.7%
2/23 • 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.
|
8.7%
2/23 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
2/23 • 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.
|
13.0%
3/23 • 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.
|
|
Blood and lymphatic system disorders
Neutropenia
|
13.0%
3/23 • 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.
|
0.00%
0/23 • 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.
|
|
Vascular disorders
Systolic hypertension
|
8.7%
2/23 • 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.
|
0.00%
0/23 • 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.
|
Additional Information
Medical Communications
Hoffmann-La Roche
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