Trial Outcomes & Findings for Effects of Cladribine Tablets on the PK of Microgynon® (NCT NCT03745144)
NCT ID: NCT03745144
Last Updated: 2024-03-15
Results Overview
Area under the plasma concentration-time curve from zero to tau at steady state (AUCt,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Results posted on
2024-03-15
Participant Flow
A total of 37 participants were screened, out of which 28 participants enrolled in the study.
Participant milestones
| Measure |
Microgynon®
Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle.
|
Sequence 1: First Cladribine, Then Placebo
Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® from Day 9-14. From Day 15-28 participants received once daily Microgynon® along with 5-day once-daily Cladribine 10 to 20 mg depending on body weight.
|
Sequence 2: First Placebo, Then Cladribine
Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® tablet once daily from Day 9-28.
Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|
|
Run-in-Period (Day 0 to Day 28)
STARTED
|
28
|
0
|
0
|
|
Run-in-Period (Day 0 to Day 28)
Safety Analysis Set
|
28
|
0
|
0
|
|
Run-in-Period (Day 0 to Day 28)
Pharmacokinetic Analysis Set
|
21
|
0
|
0
|
|
Run-in-Period (Day 0 to Day 28)
COMPLETED
|
24
|
0
|
0
|
|
Run-in-Period (Day 0 to Day 28)
NOT COMPLETED
|
4
|
0
|
0
|
|
Period 1
STARTED
|
0
|
13
|
11
|
|
Period 1
COMPLETED
|
0
|
13
|
10
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
1
|
|
Period 2
STARTED
|
0
|
13
|
10
|
|
Period 2
COMPLETED
|
0
|
13
|
10
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Microgynon®
Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle.
|
Sequence 1: First Cladribine, Then Placebo
Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® from Day 9-14. From Day 15-28 participants received once daily Microgynon® along with 5-day once-daily Cladribine 10 to 20 mg depending on body weight.
|
Sequence 2: First Placebo, Then Cladribine
Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® tablet once daily from Day 9-28.
Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|
|
Run-in-Period (Day 0 to Day 28)
Other
|
4
|
0
|
0
|
|
Period 1
Other
|
0
|
0
|
1
|
Baseline Characteristics
Effects of Cladribine Tablets on the PK of Microgynon®
Baseline characteristics by cohort
| Measure |
All Participants
n=28 Participants
All participants who received Microgynon® for 21 days and received cladribine treatment of 10 to 20 mg depending on body weight or matching placebo treatment in either of Treatment groups.
|
|---|---|
|
Age, Continuous
|
34 Years
STANDARD_DEVIATION 6.3 • n=99 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Area under the plasma concentration-time curve from zero to tau at steady state (AUCt,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel
Ethinyl Estradiol
|
789 hour*picograms per millilitre(h*pg/ml)
Geometric Coefficient of Variation 56.9
|
817 hour*picograms per millilitre(h*pg/ml)
Geometric Coefficient of Variation 52.6
|
—
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—
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—
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—
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—
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—
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—
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—
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|
Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel
Levonorgestrel
|
91400 hour*picograms per millilitre(h*pg/ml)
Geometric Coefficient of Variation 45.2
|
92000 hour*picograms per millilitre(h*pg/ml)
Geometric Coefficient of Variation 46.8
|
—
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—
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—
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—
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—
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—
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—
|
—
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Maximum observed plasma concentration in steady state (Cmax,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel
Levonorgestrel
|
7950 pg/ml
Geometric Coefficient of Variation 33.9
|
8150 pg/ml
Geometric Coefficient of Variation 34.6
|
—
|
—
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—
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—
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—
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—
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—
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—
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Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel
Ethinyl Estradiol
|
88.3 pg/ml
Geometric Coefficient of Variation 46.5
|
88.1 pg/ml
Geometric Coefficient of Variation 45.7
|
—
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—
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—
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—
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—
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—
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—
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—
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Minimum observed plasma concentration in steady state (Cmin,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel
Ethinyl Estradiol
|
14.8 pg/ml
Geometric Coefficient of Variation 66.3
|
14.7 pg/ml
Geometric Coefficient of Variation 65.6
|
—
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—
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—
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—
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—
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—
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—
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—
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Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel
Levonorgestrel
|
2520 pg/ml
Geometric Coefficient of Variation 49.5
|
2430 pg/ml
Geometric Coefficient of Variation 56.3
|
—
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—
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—
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—
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—
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—
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—
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—
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Plasma concentration at end of dosing interval at steady state (Ctrough) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel
Ethinyl Estradiol
|
15.5 pg/ml
Geometric Coefficient of Variation 66.8
|
15.4 pg/ml
Geometric Coefficient of Variation 66.9
|
—
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—
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—
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—
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—
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—
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—
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—
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Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel
Levonorgestrel
|
2580 pg/ml
Geometric Coefficient of Variation 48.5
|
2580 pg/ml
Geometric Coefficient of Variation 56.0
|
—
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—
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—
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—
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—
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—
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—
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—
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Time to reach the maximum observed plasma concentration at steady state (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel were reported. Calculated using descriptive statistics.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
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Time to Reach the Maximum Observed Plasma Concentration At Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel
Ethinyl Estradiol
|
1.00 hours
Interval 0.0 to 2.0
|
1.00 hours
Interval 0.417 to 2.0
|
—
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—
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—
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—
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—
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—
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—
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—
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Time to Reach the Maximum Observed Plasma Concentration At Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel
Levonorgestrel
|
1.00 hours
Interval 0.417 to 2.0
|
1.00 hours
Interval 0.417 to 2.0
|
—
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—
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—
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—
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—
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—
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—
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—
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PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Average plasma concentration at steady state (Cav,ss) ) of Ethinyl Estradiol and Levonorgestrel were reported. Cav,ss =AUCt,ss/ tau, where, AUCt,ss was defined as the area under the plasma concentration-time curve in steady state during a complete dosing interval (tau) and Tau is the Complete dosing interval. Calculated using descriptive statistics.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Average Plasma Concentration at Steady State (Cav,ss) of Ethinyl Estradiol and Levonorgestrel
Ethinyl Estradiol
|
32.9 pg/ml
Geometric Coefficient of Variation 56.9
|
34.1 pg/ml
Geometric Coefficient of Variation 52.6
|
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—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Average Plasma Concentration at Steady State (Cav,ss) of Ethinyl Estradiol and Levonorgestrel
Levonorgestrel
|
3810 pg/ml
Geometric Coefficient of Variation 45.2
|
3830 pg/ml
Geometric Coefficient of Variation 46.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
The PTF within complete dosing interval at steady state, calculated as PTF (%) = (\[Cmax - Cmin\]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=21 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Peak-to-Trough Fluctuation Over One Complete Dosing Interval At Steady State (PTF%)
Ethinyl Estradiol
|
220 percentage fluctuation
Geometric Coefficient of Variation 28.0
|
213 percentage fluctuation
Geometric Coefficient of Variation 23.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Peak-to-Trough Fluctuation Over One Complete Dosing Interval At Steady State (PTF%)
Levonorgestrel
|
140 percentage fluctuation
Geometric Coefficient of Variation 29.7
|
145 percentage fluctuation
Geometric Coefficient of Variation 29.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to Day 84Population: Safety Analysis Set included all participant who were administered any dose of the trial medication.
Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.
Outcome measures
| Measure |
Microgynon + Cladribine
n=28 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=13 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
n=13 Participants
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
n=13 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
n=13 Participants
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
n=13 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
n=11 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
n=10 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment -Emergent Adverse Events (TEAEs)
|
7 Participants
|
3 Participants
|
9 Participants
|
5 Participants
|
5 Participants
|
4 Participants
|
1 Participants
|
5 Participants
|
1 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Up to Day 84Population: Safety Analysis Set included all participant who were administered any dose of the trial medication.
Laboratory investigation included hematology, biochemistry and urinalysis. Clinical relevance was decided by the investigator. Number of participants with clinically relevant change from baseline in laboratory values were reported.
Outcome measures
| Measure |
Microgynon + Cladribine
n=28 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=13 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
n=13 Participants
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
n=13 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
n=13 Participants
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
n=13 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
n=11 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
n=10 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Relevant Change From Baseline in Laboratory Values
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 84Population: Safety Analysis Set included all participant who were administered any dose of the trial medication.
The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula. Clinical Relevance was decided by the investigator. Number of participants with clinical relevant change from baseline in ECG parameters were reported.
Outcome measures
| Measure |
Microgynon + Cladribine
n=28 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=13 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
n=13 Participants
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
n=13 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
n=13 Participants
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
n=13 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
n=11 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
n=10 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Relevant Change From Baseline in Electrocardiogram (ECG)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 84Population: Safety Analysis Set included all participant who were administered any dose of the trial medication.
Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. Clinical Relevance was decided by the investigator. Number of participants with clinically relevant change from baseline in vital signs were reported.
Outcome measures
| Measure |
Microgynon + Cladribine
n=28 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
n=13 Participants
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
n=13 Participants
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
n=13 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
n=13 Participants
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
n=13 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
n=11 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
n=10 Participants
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
n=10 Participants
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Relevant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Cmax was obtained from plasma concentration time curve.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Cladribine
Day 10
|
29.3 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 39.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Cladribine
Day 11
|
28.2 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 45.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Cladribine
Day 12
|
23.6 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 37.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) of Cladribine
Day 13
|
22.7 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 40.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13Population: Pharmacokinetic Analysis Set included all participants in the Safety Set without clinically important protocol deviations/violations and absence of factors/events likely to affect Pharmacokinetics (PK).
Tmax was obtained from plasma concentration time curve.
Outcome measures
| Measure |
Microgynon + Cladribine
n=21 Participants
Participants received once-daily Cladribine at a dose of 10 milligrams (mg) or 20 mg from Day 9 to Day 13 in period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 micrograms \[mcg\], levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Microgynon + Placebo
Participants received 5-day once daily cladribine matched placebo from Day 15 to Day 19 in Period 1 and from Day 15 to Day 19 in Period 2 along with Microgynon® tablet (ethinyl estradiol 30 mcg, levonorgestrel 150 mcg) once daily from Day 1 to Day 21 in either treatment period 1 or period 2.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
Day 10
|
0.500 hours
Interval 0.5 to 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
Day 11
|
0.500 hours
Interval 0.25 to 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
Day 12
|
0.500 hours
Interval 0.5 to 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
Day 13
|
0.500 hours
Interval 0.25 to 2.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Run-in Period: Microgynon (Day -28 to -1)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Sequence 1 Period 1: Microgynon Alone (Day 1-8)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Run-in Period: Microgynon (Day -28 to -1)
n=28 participants at risk
Participants received Microgynon for 21 days, starting on the first day of the menstrual cycle.
|
Sequence 1 Period 1: Microgynon Alone (Day 1-8)
n=13 participants at risk
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)
n=13 participants at risk
Participants received 5-day once daily dose of Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
Sequence 1 Period 2: Microgynon Alone (Day 1-8)
n=13 participants at risk
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)
n=13 participants at risk
Participants received 5-day once daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-14.
|
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)
n=13 participants at risk
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 15-28.
|
Sequence 2 Period 1: Microgynon Alone (Day 1-8)
n=11 participants at risk
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)
n=10 participants at risk
Participants received 5-day once-daily dose of Cladribine matched Placebo along with Microgynon® from Day 9-28.
|
Sequence 2 Period 2: Microgynon Alone (Day 1-8)
n=10 participants at risk
Participants received a single once daily dose of Microgynon® tablet from Day 1-8.
|
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)
n=10 participants at risk
Participants received 5-day once-daily dose of Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Blood and lymphatic system disorders
Lymphocytosis
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
General disorders
Fatigue
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
15.4%
2/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
20.0%
2/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
30.0%
3/10 • Up to Day 84
|
|
Infections and infestations
Tonsilitis
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Infections and infestations
Urinary Tract Infection
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Investigations
Haematocrit Decreased
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Nervous system disorders
Headache
|
10.7%
3/28 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
46.2%
6/13 • Up to Day 84
|
23.1%
3/13 • Up to Day 84
|
15.4%
2/13 • Up to Day 84
|
23.1%
3/13 • Up to Day 84
|
9.1%
1/11 • Up to Day 84
|
30.0%
3/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
30.0%
3/10 • Up to Day 84
|
|
Nervous system disorders
Migraine
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Reproductive system and breast disorders
Hypomenorrhoea
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Reproductive system and breast disorders
Intermenstrual Bleeding
|
7.1%
2/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.6%
1/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Cardiac disorders
Sinus Bradycardia
|
0.00%
0/28 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
General disorders
Chills
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
General disorders
Feeling Cold
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
General disorders
Mucosal Dryness
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
General disorders
Pain
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/28 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Nervous system disorders
Multiple Sclerosis Relapse
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Psychiatric disorders
Sleep Disorder
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Infections and infestations
Vaginal Infection
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Investigations
Blood Pressure Increased
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Eye disorders
Eye Pruritus
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Eye disorders
Lacrimation Increased
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Eye disorders
Vision Blurred
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
20.0%
2/10 • Up to Day 84
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
General disorders
Asthenia
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
General disorders
Pyrexia
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Injury, poisoning and procedural complications
Tooth Fracture
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Investigations
Alanine Aminotransferase Increased
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Investigations
Blood Creatine Phosphokinase MB Increased
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Investigations
Low Density Lipoprotein Increased
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Investigations
Weight Decreased
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Musculoskeletal and connective tissue disorders
Joint Swelling
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Nervous system disorders
Meralgia Paraesthetica
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
7.7%
1/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/28 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/13 • Up to Day 84
|
0.00%
0/11 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
0.00%
0/10 • Up to Day 84
|
10.0%
1/10 • Up to Day 84
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Phone: +49 6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER