Trial Outcomes & Findings for Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19 and CYP3A4 (NCT NCT04246762)

NCT ID: NCT04246762

Last Updated: 2024-08-15

Results Overview

Area under the AUC from time zero extrapolated to infinity, calculated by linear up/log down trapezoidal summation. In case of anomalous predose concentration of greater than 5% of Cmax was indicated, the PK parameters for the affected analyte and given subject were excluded from the analyses. Since caffeine is contained in the plethora of foods and beverages, most subjects had predose caffeine concentrations on Day 1 and Day 22 that exceeded 5% of their Maximum plasma concentration (Cmax). Caffeine PK parameter calculations and analyses were performed using concentrations adjusted by subtracting the contribution of the predose caffeine levels at each postdose timepoint using the following equation: Concentration (adjusted) = Concentration (observed) - \[C predose \* exp(-k\*t)\], with 'k' representing the patient-specific elimination rate constant (λz) determined using observed caffeine concentration data on Day 1 and Day 22 and 't' representing the actual time postdose.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 17 participants
• Primary outcome timeframe: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24 (Day 2), 30 (Day 2, only caffeine) hours post-dose; Day 22: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24 (Day 23), 30 (Day 23, only caffeine) hours post-dose
• Results posted on: 2024-08-15

Participant Flow

Enrollment was conducted at 2 sites in 2 countries (Bulgaria and Moldova). A total of 17 subjects were enrolled into Period 1 of the study and 16 subjects each were enrolled into Period 2 and Period 3 of the study. All 17 subjects who received the first dose were enrolled into Safety Analysis Set and 16 subjects were enrolled into Pharmacokinetics (PK) and Pharmacodynamics (PD) Analysis Sets.

Participant milestones

Measure	Olokizumab 128 mg + Cocktail Drugs All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Period 1: Cocktail Alone STARTED	17
Period 1: Cocktail Alone COMPLETED	16
Period 1: Cocktail Alone NOT COMPLETED	1
Period 2: Olokizumab Administration STARTED	16
Period 2: Olokizumab Administration COMPLETED	16
Period 2: Olokizumab Administration NOT COMPLETED	0
Period 3: Olokizumab + Cocktail STARTED	16
Period 3: Olokizumab + Cocktail COMPLETED	16
Period 3: Olokizumab + Cocktail NOT COMPLETED	0
Safety Follow-up STARTED	16
Safety Follow-up COMPLETED	16
Safety Follow-up NOT COMPLETED	0

Reasons for withdrawal

Measure

Olokizumab 128 mg + Cocktail Drugs All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.

Period 1: Cocktail Alone Protocol Violation

1

Baseline Characteristics

Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19 and CYP3A4

Baseline characteristics by cohort

Measure	Olokizumab 128 mg + Cocktail Drugs n=17 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Age, Continuous	51.1 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Body Mass Index (BMI)	27.58 kg/m^2 n=5 Participants
C-reactive protein (CRP)	21.996 mg/L STANDARD_DEVIATION 33.0943 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24 (Day 2), 30 (Day 2, only caffeine) hours post-dose; Day 22: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24 (Day 23), 30 (Day 23, only caffeine) hours post-dose

Population: These subjects were excluded: For 1 subject the Percentage of AUC(0-inf) obtained by extrapolation (%AUCex) was \> 20.0 % for midazolam on Day 1. 1 subject had a quantifiable predose concentration of Omeprazole on Day 1 that exceeded 5% of Cmax. For 3 subjects the %AUCex exceeded 20.0 % for baseline-adjusted caffeine on Day 22 and for 1 subject - on Day 1 also. For 1 subject λz calculated from the observed caffeine concentration data on Day 1 was not adequate for baseline adjustment purposes.

Area under the AUC from time zero extrapolated to infinity, calculated by linear up/log down trapezoidal summation.

In case of anomalous predose concentration of greater than 5% of Cmax was indicated, the PK parameters for the affected analyte and given subject were excluded from the analyses.

Since caffeine is contained in the plethora of foods and beverages, most subjects had predose caffeine concentrations on Day 1 and Day 22 that exceeded 5% of their Maximum plasma concentration (Cmax). Caffeine PK parameter calculations and analyses were performed using concentrations adjusted by subtracting the contribution of the predose caffeine levels at each postdose timepoint using the following equation: Concentration (adjusted) = Concentration (observed) - [C predose * exp(-k*t)], with 'k' representing the patient-specific elimination rate constant (λz) determined using observed caffeine concentration data on Day 1 and Day 22 and 't' representing the actual time postdose.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC(0-inf)) for Caffeine, Omeprazole and Midazolam Midazolam	38.23 h*ng/mL Interval 30.32 to 48.21
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC(0-inf)) for Caffeine, Omeprazole and Midazolam Midazolam + OKZ	26.94 h*ng/mL Interval 21.43 to 33.86
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC(0-inf)) for Caffeine, Omeprazole and Midazolam Omeprazole	1408 h*ng/mL Interval 933.5 to 2124.0
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC(0-inf)) for Caffeine, Omeprazole and Midazolam Omeprazole + OKZ	955.8 h*ng/mL Interval 635.3 to 1438.0
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC(0-inf)) for Caffeine, Omeprazole and Midazolam Caffeine (baseline-adjusted)	21820 h*ng/mL Interval 17610.0 to 27040.0
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC(0-inf)) for Caffeine, Omeprazole and Midazolam Caffeine + OKZ (baseline-adjusted)	26830 h*ng/mL Interval 21580.0 to 33340.0

PRIMARY outcome

Timeframe: Day 1: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24(Day 2), 48(Day 3), 72 (Day 4), 120 (Day 6), 168 (Day 8) hours post-dose; Day 22: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24(Day 23), 48(Day 24), 72 (Day 25), 120 (Day 27), 168 (Day 29) hours post-dose

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, calculated by linear up/log down trapezoidal summation for S-warfarin (10 mg warfarin contains 5 mg S-warfarin)

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
AUC From Time Zero to the Time "t" (AUC(0-last)) for S-warfarin S-Warfarin	21350 h*ng/mL Interval 18360.0 to 24820.0
AUC From Time Zero to the Time "t" (AUC(0-last)) for S-warfarin S-Warfarin + OKZ	19390 h*ng/mL Interval 16680.0 to 22540.0

PRIMARY outcome

Timeframe: Day 1: pre-dose, 0.5 - 24, 30 (only caffeine), 48 (only S-warfarin), 72 (only S-warfarin), 120 (only S-warfarin), 168 (only S-warfarin) hours post-dose; Day 22: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose

Population: One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax and all PK parameters were excluded from summary presentations and statistical analysis for that study day. For one subject lambda-z (observed) of caffeine was not adequate for baseline adjustment and Cmax was excluded from summary presentations and statistical analysis.

Cmax for all cocktail substrates (caffeine, omeprazole, midazolam and S-warfarin), obtained directly from the observed concentration versus time data.

In case of anomalous predose concentration of greater than 5% of Cmax was indicated, the PK parameters for the affected analyte and given subject were excluded from the analyses.

Since caffeine is contained in the plethora of foods and beverages, most subjects had predose caffeine concentrations on Day 1 and Day 22 that exceeded 5% of their Cmax. Caffeine PK parameter calculations and analyses were performed using concentrations adjusted by subtracting the contribution of the predose caffeine levels at each postdose timepoint using the following equation: Concentration (adjusted) = Concentration (observed) - [C predose * exp(-k*t)], with 'k' representing the patient-specific elimination rate constant (λz) determined using observed caffeine concentration data on Day 1 and Day 22 and 't' representing the actual time postdose.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates Midazolam	13.29 ng/mL Interval 11.08 to 15.93
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates Midazolam + OKZ	9.101 ng/mL Interval 7.593 to 10.91
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates Omeprazole	668.6 ng/mL Interval 522.4 to 855.6
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates Omeprazole + OKZ	491.7 ng/mL Interval 385.2 to 627.7
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates Caffeine (baseline adjusted)	2803 ng/mL Interval 2570.0 to 3057.0
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates Caffeine + OKZ (baseline adjusted)	2746 ng/mL Interval 2523.0 to 2990.0
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates S-Warfarin	627.0 ng/mL Interval 571.5 to 688.0
Maximum Plasma Concentration (Cmax) for All Cocktail Substrates S-Warfarin + OKZ	641.5 ng/mL Interval 584.6 to 703.9

SECONDARY outcome

Timeframe: Day 1: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24 (Day 2), 30 (Day 2, only caffeine) hours post-dose; Day 22: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24 (Day 23), 30 (Day 23, only caffeine) hours post-dose

Population: One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax and all PK parameters were excluded from summary presentations and statistical analysis for that study day. For one subject lambda-z (observed) of caffeine was not adequate for baseline adjustment and AUC(0-last) was excluded from summary presentations and statistical analysis.

AUC from time zero to the time of the last quantifiable concentration, calculated by linear up/log down trapezoidal summation for Caffeine, Omeprazole, Midazolam.

In case of anomalous predose concentration of greater than 5% of Cmax was indicated, the PK parameters for the affected analyte and given subject were excluded from the analyses. Since caffeine is contained in the plethora of foods and beverages, most subjects had predose caffeine concentrations on Day 1 and Day 22 that exceeded 5% of their Cmax. Caffeine PK parameter calculations and analyses were performed using concentrations adjusted by subtracting the contribution of the predose caffeine levels at each postdose timepoint using the following equation: Concentration (adjusted) = Concentration (observed) - [C predose * exp(-k*t)], with 'k' representing the patient-specific elimination rate constant (λz) determined using observed caffeine concentration data on Day 1 and Day 22 and 't' representing the actual time postdose.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Plasma AUC(0-last) for Cocktail Parent Compounds (for Caffeine, Omeprazole and Midazolam) Midazolam	36.77 h*ng/mL Geometric Coefficient of Variation 43.0
Plasma AUC(0-last) for Cocktail Parent Compounds (for Caffeine, Omeprazole and Midazolam) Midazolam + OKZ	24.73 h*ng/mL Geometric Coefficient of Variation 49.6
Plasma AUC(0-last) for Cocktail Parent Compounds (for Caffeine, Omeprazole and Midazolam) Omeprazole	1461 h*ng/mL Geometric Coefficient of Variation 92.2
Plasma AUC(0-last) for Cocktail Parent Compounds (for Caffeine, Omeprazole and Midazolam) Omeprazole + OKZ	951.1 h*ng/mL Geometric Coefficient of Variation 86.3
Plasma AUC(0-last) for Cocktail Parent Compounds (for Caffeine, Omeprazole and Midazolam) Caffeine (baseline-adjusted)	21860 h*ng/mL Geometric Coefficient of Variation 42.2
Plasma AUC(0-last) for Cocktail Parent Compounds (for Caffeine, Omeprazole and Midazolam) Caffeine (baseline-adjusted) + OKZ	26910 h*ng/mL Geometric Coefficient of Variation 42.8

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24, 48, 72, 120, 168 hours post-dose; Day 22: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 7, 12, 24, 48, 72, 120, 168 hours post-dose

Area under the plasma concentration-time curve from time zero extrapolated to infinity, calculated by linear up/log down trapezoidal summation for S-warfarin (10 mg warfarin contains 5 mg S-warfarin).

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Plasma AUC From Time Zero to Infinity (AUC(0-inf)) for Cocktail Parent Compounds (for S-warfarin) S-warfarin	21350 h*ng/mL Geometric Coefficient of Variation 29.4
Plasma AUC From Time Zero to Infinity (AUC(0-inf)) for Cocktail Parent Compounds (for S-warfarin) S-warfarin + OKZ	19390 h*ng/mL Geometric Coefficient of Variation 28.7

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.5 - 24, 30 (only caffeine), 48 (only S-warfarin), 72 (only S-warfarin), 120 (only S-warfarin), 168 (only S-warfarin) hours post-dose; Day 22: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose

Population: One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax and all PK parameters were excluded from summary presentations and statistical analysis for that study day. For one subject lambda-z (observed) of caffeine was not adequate for baseline adjustment and tmax was excluded from summary presentations and statistical analysis.

tmax for cocktail parent compounds (caffeine, S-warfarin, omeprazole and midazolam), obtained directly from the observed concentration versus time data.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds Midazolam	0.500 hours Interval 0.48 to 1.03
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds Midazolam + OKZ	0.533 hours Interval 0.5 to 1.03
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds Omeprazole	2.000 hours Interval 1.0 to 3.03
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds Omeprazole + OKZ	2.000 hours Interval 1.0 to 4.03
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds Caffeine (baseline-adjusted)	0.533 hours Interval 0.23 to 2.0
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds Caffeine (baseline-adjusted) + OKZ	0.558 hours Interval 0.5 to 2.03
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds S-Warfarin	1.500 hours Interval 0.5 to 3.03
Time to Maximum Plasma Concentration (Tmax) for Cocktail Parent Compounds S-Warfarin + OKZ	1.500 hours Interval 0.25 to 4.0

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose; Day 22: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose

Population: One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax and all PK parameters were excluded from summary presentations and statistical analysis for that study day. For one subject lambda-z (observed) of caffeine was not adequate for baseline adjustment and t1/2 was excluded from summary presentations and statistical analysis.

Terminal half-life (t1/2) for cocktail parent compounds (caffeine, S-warfarin (10 mg warfarin contains 5 mg S-warfarin), omeprazole, and midazolam)

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Terminal Half-life (t1/2) for Cocktail Parent Compounds Midazolam	6.726 hours Geometric Coefficient of Variation 28.6
Terminal Half-life (t1/2) for Cocktail Parent Compounds Omeprazole	1.279 hours Geometric Coefficient of Variation 59.8
Terminal Half-life (t1/2) for Cocktail Parent Compounds Omeprazole + OKZ	0.9859 hours Geometric Coefficient of Variation 51.5
Terminal Half-life (t1/2) for Cocktail Parent Compounds Caffeine (baseline-adjusted)	6.375 hours Geometric Coefficient of Variation 43.1
Terminal Half-life (t1/2) for Cocktail Parent Compounds Caffeine (baseline-adjusted) + OKZ	8.046 hours Geometric Coefficient of Variation 48.2
Terminal Half-life (t1/2) for Cocktail Parent Compounds S-Warfarin	43.94 hours Geometric Coefficient of Variation 13.6
Terminal Half-life (t1/2) for Cocktail Parent Compounds S-Warfarin + OKZ	38.57 hours Geometric Coefficient of Variation 14.6
Terminal Half-life (t1/2) for Cocktail Parent Compounds Midazolam + OKZ	6.520 hours Geometric Coefficient of Variation 32.8

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose; Day 22: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose

Population: One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax and all PK parameters were excluded from summary presentations and statistical analysis for that study day. For one subject lambda-z (observed) of caffeine was not adequate for baseline adjustment.

elimination rate constant (λz) for cocktail parent compounds (caffeine, S-warfarin (10 mg warfarin contains 5 mg S-warfarin), omeprazole, and midazolam), determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin was used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Elimination Rate Constant (λz) for Cocktail Parent Compounds Midazolam	0.1031 1/hours Geometric Coefficient of Variation 28.6
Elimination Rate Constant (λz) for Cocktail Parent Compounds Midazolam + OKZ	0.1063 1/hours Geometric Coefficient of Variation 32.8
Elimination Rate Constant (λz) for Cocktail Parent Compounds Omeprazole	0.5418 1/hours Geometric Coefficient of Variation 59.8
Elimination Rate Constant (λz) for Cocktail Parent Compounds Omeprazole + OKZ	0.7031 1/hours Geometric Coefficient of Variation 51.5
Elimination Rate Constant (λz) for Cocktail Parent Compounds Caffeine (baseline-adjusted)	0.1087 1/hours Geometric Coefficient of Variation 43.1
Elimination Rate Constant (λz) for Cocktail Parent Compounds Caffeine (baseline-adjusted) + OKZ	0.08615 1/hours Geometric Coefficient of Variation 48.2
Elimination Rate Constant (λz) for Cocktail Parent Compounds S-Warfarin	0.01578 1/hours Geometric Coefficient of Variation 13.6
Elimination Rate Constant (λz) for Cocktail Parent Compounds S-Warfarin + OKZ	0.01797 1/hours Geometric Coefficient of Variation 14.6

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose; Day 22: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose

Population: These subjects were excluded: For one subject the %AUCex was \> 20.0% for midazolam on Day 1. For 3 subjects the %AUCex exceeded 20.0 % for baseline-adjusted caffeine on Day 22 and for 1 subject - on Day 1 also. For 1 subject λz calculated from the observed caffeine concentration data on Day 1 was not adequate for baseline adjustment purposes. One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax.

Apparent systemic clearance (CL/F) for cocktail parent compounds (caffeine, omeprazole, and midazolam), calculated as dose divided by AUC(0-inf).

In case of anomalous predose concentration of greater than 5% of Cmax was indicated, the PK parameters for the affected analyte and given subject were excluded from the analyses. Since caffeine is contained in the plethora of foods and beverages, most subjects had predose caffeine concentrations on Day 1 and Day 22 that exceeded 5% of their Cmax. Caffeine PK parameter calculations and analyses were performed using concentrations adjusted by subtracting the contribution of the predose caffeine levels at each postdose timepoint using the following equation: Concentration (adjusted) = Concentration (observed) - [C predose * exp(-k*t)], with 'k' representing the patient-specific elimination rate constant (λz) determined using observed caffeine concentration data on Day 1 and Day 22 and 't' representing the actual time postdose.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Apparent Systemic Clearance (CL/F) for Cocktail Parent Compounds Midazolam	53.23 L/hours Geometric Coefficient of Variation 41.4
Apparent Systemic Clearance (CL/F) for Cocktail Parent Compounds Midazolam + OKZ	74.24 L/hours Geometric Coefficient of Variation 50.2
Apparent Systemic Clearance (CL/F) for Cocktail Parent Compounds Omeprazole	13.58 L/hours Geometric Coefficient of Variation 94.3
Apparent Systemic Clearance (CL/F) for Cocktail Parent Compounds Omeprazole + OKZ	20.93 L/hours Geometric Coefficient of Variation 86.9
Apparent Systemic Clearance (CL/F) for Cocktail Parent Compounds Caffeine (baseline-adjusted)	4.582 L/hours Geometric Coefficient of Variation 37.9
Apparent Systemic Clearance (CL/F) for Cocktail Parent Compounds Caffeine (baseline-adjusted) + OKZ	3.805 L/hours Geometric Coefficient of Variation 40.9

SECONDARY outcome

Timeframe: Day 1: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose; Day 22: pre-dose, 0.5 - 24, 30 (only caffeine), 48 - 168 (only S-warfarin) hours post-dose

Population: These subjects were excluded: For one subject the %AUCex was \> 20.0% for midazolam on Day 1. For 3 subjects the %AUCex exceeded 20.0 % for baseline-adjusted caffeine on Day 22 and for 1 subject - on Day 1 also. For 1 subject λz calculated from the observed caffeine concentration data on Day 1 was not adequate for baseline adjustment purposes. One subject had a quantifiable predose concentration of omeprazole on Day 1 that exceeded 5% of Cmax.

Vz/F during terminal phase for cocktail parent compounds (caffeine, omeprazole and midazolam), calculated as dose divided by [λz *AUC(0-inf)] In case of anomalous predose concentration of greater than 5% of Cmax was indicated, the PK parameters for the affected analyte and given subject were excluded from the analyses. Since caffeine is contained in the plethora of foods and beverages, most subjects had predose caffeine concentrations on Day 1 and Day 22 that exceeded 5% of their Cmax. Caffeine PK parameter calculations and analyses were performed using concentrations adjusted by subtracting the contribution of the predose caffeine levels at each postdose timepoint using the following equation: Concentration (adjusted) = Concentration (observed) - [C predose * exp(-k*t)], with 'k' representing the patient-specific elimination rate constant (λz) determined using observed caffeine concentration data on Day 1 and Day 22 and 't' representing the actual time postdose.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Apparent Volume of Distribution (Vz/F) for Cocktail Parent Compounds Midazolam	492.6 L Geometric Coefficient of Variation 35.4
Apparent Volume of Distribution (Vz/F) for Cocktail Parent Compounds Omeprazole	25.06 L Geometric Coefficient of Variation 31.4
Apparent Volume of Distribution (Vz/F) for Cocktail Parent Compounds Caffeine (baseline-adjusted)	38.86 L Geometric Coefficient of Variation 19.9
Apparent Volume of Distribution (Vz/F) for Cocktail Parent Compounds Caffeine (baseline-adjusted) + OKZ	37.70 L Geometric Coefficient of Variation 37.70
Apparent Volume of Distribution (Vz/F) for Cocktail Parent Compounds Midazolam + OKZ	698.3 L Geometric Coefficient of Variation 43.3
Apparent Volume of Distribution (Vz/F) for Cocktail Parent Compounds Omeprazole + OKZ	29.76 L Geometric Coefficient of Variation 33.4

SECONDARY outcome

Timeframe: Predose: within 30 min of OKZ administration on Day 8; postdose: Day 9, Day 15 (sample collection clock-matched to Day 8 sample), Day 22 (collected prior to administration of DDI cocktail), Day 24, Day 29 (sample collection clock-matched to Day 22 sample)

Maximum concentration obtained directly from the observed concentration versus time data for Olokizumab.

Outcome measures

Measure

Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.

Plasma Concentrations (Cmax) for Olokizumab

15670 ng/mL Interval 5030.0 to 24100.0

SECONDARY outcome

Timeframe: Days 1, 8, 9, 15, 22, 29

Blood sampling for the measurement of IL-6 were performed at Screening, prior to dosing with the cocktail on Day 1, prior to dose administration with OKZ on Day 8, and post OKZ dose administration on Day 9, Day 15, Day 22 (prior to dose administration of the cocktail on Day 22), and Day 29, which were considered the EOT visit.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Baseline	26.224 pg/mL Standard Deviation 35.0576
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Day 8	16.414 pg/mL Standard Deviation 20.2591
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 8	-9.810 pg/mL Standard Deviation 34.8049
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Day 9	2.518 pg/mL Standard Deviation 1.2827
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 9	-23.706 pg/mL Standard Deviation 35.4123
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Day 22	6.796 pg/mL Standard Deviation 7.5603
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 22	-19.429 pg/mL Standard Deviation 35.4360
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Day 29	5.699 pg/mL Standard Deviation 4.8192
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 29	-20.526 pg/mL Standard Deviation 34.8727
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Day 15	6.434 pg/mL Standard Deviation 6.7420
Change in Interleukin-6 (IL-6) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 15	-19.790 pg/mL Standard Deviation 35.0774

SECONDARY outcome

Timeframe: Days 1, 8, 9, 15, 22, 29

Blood sampling for the measurement of CRP were performed at Screening, prior to dosing with the cocktail on Day 1, prior to dose administration with OKZ on Day 8, and post OKZ dose administration on Day 9, Day 15, Day 22 (prior to dose administration of the cocktail on Day 22), and Day 29, which were considered the EOT visit.

Outcome measures

Measure	Olokizumab 128 mg + Cocktail Drugs n=16 Participants All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Baseline	22.969 mg/L Standard Deviation 33.9274
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Day 8	15.153 mg/L Standard Deviation 15.3990
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 8	-7.817 mg/L Standard Deviation 26.8275
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Day 9	11.783 mg/L Standard Deviation 11.5188
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 9	-11.187 mg/L Standard Deviation 29.3898
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Day 15	2.266 mg/L Standard Deviation 2.0937
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 15	-20.703 mg/L Standard Deviation 34.3184
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Day 22	2.044 mg/L Standard Deviation 2.5411
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 22	-20.926 mg/L Standard Deviation 34.5988
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Day 29	2.312 mg/L Standard Deviation 2.8719
Change in C-reactive Protein (CRP) Concentrations Collected Periodically Throughout the Study Change from Baseline on Day 29	-20.657 mg/L Standard Deviation 34.8682

Adverse Events

Olokizumab 128 mg + Cocktail Drugs

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Olokizumab 128 mg + Cocktail Drugs n=17 participants at risk All subjects have received the following treatment: Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered with 240 mL of water on Day 1 (Period 1), single subcutaneous injection of Olokizumab 128 mg administered on Day 8 (Period 2) and second dose of Cocktail drugs (Omeprazole + Caffeine + Warfarin (+ vitamin K solution) + Midazolam) orally administered on Day 22 (Period 3). Olokizumab: Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection); Omeprazole: Tablets, 20 mg, oral; Caffeine: Tablets, 100 mg, oral; Warfarin + Vitamin K: Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral; Vitamin K - solution for intravenous injection, 10 mg/mL ampoule (orally); Midazolam: Syrup, 2 mg/mL, oral.
Blood and lymphatic system disorders Anaemia	11.8% 2/17 • Number of events 2 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.
Gastrointestinal disorders Nausea	5.9% 1/17 • Number of events 1 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.
Hepatobiliary disorders Drug-Induced Liver Injury	5.9% 1/17 • Number of events 1 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.
Infections and infestations Urinary Tract Infection	11.8% 2/17 • Number of events 2 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.
Investigations Blood Cholesterol Increased	5.9% 1/17 • Number of events 1 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.
Investigations Lymphocyte Count Decreased	5.9% 1/17 • Number of events 1 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.
Investigations White Blood Cell Count Decreased	5.9% 1/17 • Number of events 1 • From the signing of the Informed Consent Form (ICF) until the final end of study (EOS) telephonic follow-up visit (Day 161 ±10 days) Safety population included all subjects who received at least 1 dose of study treatment (CYP450 probe cocktail or OKZ). Subjects were analyzed according to the treatment they received.

Additional Information

Marina Beloukhova, Scientific advisor

R-Pharm

Phone: 0074959567937

Email: beloukhova@rpharm.ru

Results disclosure agreements

• Principal investigator is a sponsor employee Any study related information could be made public available only after Sponsors written permission.
• Publication restrictions are in place

Restriction type: OTHER