Relapsing Multiple Sclerosis (RMS)Phase 1NCT03745144

Effects of Cladribine Tablets on the PK of Microgynon®

A Phase 1 study testing Cladribine and Microgynon® in people with Relapsing Multiple Sclerosis (RMS), run by Merck KGaA, Darmstadt, Germany at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study was to investigate the potential effects of cladribine on the pharmacokinetics (PK) of monophasic oral contraceptive microgynon® by assessment of its constituents, ethinyl estradiol (EE) and levonorgestrel (LNG). Read more about this study

Who is it for?: Ages 18 to 45 years, women only
Conditions the study is for: Relapsing Multiple Sclerosis (RMS)
What is being tested?: Cladribine and Microgynon®
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 28 participants
Where: 7 sitesin 2 countries
Study dates: 17 Jan 2019to 16 Sep 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
Women only
No healthy volunteers
Adult

Who may be able to join

Are pre-menopausal women with or without child-bearing potential with a negative serum pregnancy test, and women with child-bearing potential receiving adequate birth control
Participants with diagnosis of clinically stable and definite relapsing multiple sclerosis (RMS)
Adequate hematological, hepatic and renal function as defined in the protocol
Are able and willing to accept dietary restrictions and restrictions regarding the use of concomitant medications (including over-the-counter products, herbal medicines and dietary supplements) over the course of the study
Had a body weight and body mass index (BMI) within the range at screening
Other protocol defined inclusion criteria could apply

Who cannot join

History of clinically relevant allergy or known hypersensitivity to the active substance or to any of the excipients of cladribine tablets or hypersensitivity to drugs with a similar chemical structure to cladribine - History of clinically relevant allergy or known hypersensitivity to 1 of the active substances levonorgestrel (LNG) or ethinylestradiol (EE) or to any excipients of Microgynon® tablets
Positive results from serology examination for Hepatitis B surface antigen (HbsAg) not due to vaccination, hepatitis B core antibody (HbcAb), Hepatitis C virus antibody (anti- HCV) or Human Immunodeficiency antibody (anti-HIV)
Presence or risk of venous thromboembolism (VTE) arterial thromboembolism (ATE)
Diabetes mellitus (Type 1 or Type 2) with vascular manifestations
Signs or symptoms of neurological disease other than multiple sclerosis (MS) that could explain the symptoms of the participant
Presence of gastrointestinal (GI) disease or history of gastrointestinal -tract surgery
Exposure to another investigational drug within the last 2 months or within last 6 month if agent is known to be immunosuppressive
Other protocol defined exclusion criteria could apply

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

Poland5 sites

M.A. - LEK A.M.Maciejowscy SC.
Katowice
BioResearch Group Sp. z o. o
Nadarzyn
IKARDIA Hospital Cardiology
Nałęczów
BioVirtus Research Site Sp
Otwock
MTZ Clinical Research Sp. z o.o.
Warsaw

Other trials in Poland

Germany2 sites

St. Josef und St. Elisabeth Hospital gGmbH
Bochum
Nuvisan GmbH
Neu-Ulm

Other trials in Germany

About this study

Official title: A Randomized, Double-blind, 2-Period, 2-Sequence Crossover Phase I Study With a 1 Month run-in Period to Examine the Effect of Cladribine Tablets on the PK of a Monophasic Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel (Microgynon®) in Pre-Menopausal Women With RMS

Conditions: Relapsing Multiple Sclerosis (RMS)
Being tested: Cladribine, Placebo, Microgynon®
Keywords: Multiple Sclerosis, Cladribine, Microgynon®
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CladribineDrug
Participants received cladribine once-daily for 5 consecutive days in treatment period 1 and 2.
PlaceboDrug
Participants received placebo matched to cladribine once-daily for 5 consecutive days in treatment period 1 and 2.
Microgynon®Drug
Participants received Microgynon® tablet once daily for 21 days in treatment period 1 and 2. Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle in Run-in period.

Study groups in NCT03745144
Study group	Role	What they receive
Sequence 1: First Cladribine, Then Placebo	Experimental	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. Receives: Drug: Cladribine; Drug: Placebo; Drug: Microgynon®
Sequence 2: First Placebo, Then Cladribine	Experimental	Participants 5-day once daily 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. Receives: Drug: Cladribine; Drug: Placebo; Drug: Microgynon®
Microgynon®	Experimental	Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle. Receives: Drug: Microgynon®

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel
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.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel
Maximum observed plasma concentration in steady state (Cmax,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel
Minimum observed plasma concentration in steady state (Cmin,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel
Plasma concentration at end of dosing interval at steady state (Ctrough) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Time to Reach the Maximum Observed Plasma Concentration At Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel
Time to reach the maximum observed plasma concentration at steady state (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel were reported. Calculated using descriptive statistics.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Average Plasma Concentration at Steady State (Cav,ss) of Ethinyl Estradiol and Levonorgestrel
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.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Peak-to-Trough Fluctuation Over One Complete Dosing Interval At Steady State (PTF%)
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.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

Secondary outcomes (6)

Number of Participants With Treatment -Emergent Adverse Events (TEAEs)
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.
Measured: Up to Day 84
Number of Participants With Clinically Relevant Change From Baseline in Laboratory Values
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.
Measured: Up to Day 84
Number of Participants With Clinically Relevant Change From Baseline in Electrocardiogram (ECG)
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.
Measured: Up to Day 84
Number of Participants With Clinically Relevant Change From Baseline in Vital Signs
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.
Measured: Up to Day 84
Maximum Plasma Concentration (Cmax) of Cladribine
Cmax was obtained from plasma concentration time curve.
Measured: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
Tmax was obtained from plasma concentration time curve.
Measured: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jan 201916 Sep 2022

First posted19 Nov 2018
Study start17 Jan 2019
Primary completion2 Sep 2022
Study completion16 Sep 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Relapsing Multiple Sclerosis (RMS)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03745144
Sponsor's protocol ID: MS700568_0031
Other IDs: 2018-001015-70, 2018
Status last verified: Aug 2023
First submitted: 14 Nov 2018
Last updated: 15 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, 2-Period, 2-Sequence Crossover Phase I Study With a 1 Month run-in Period to Examine the Effect of Cladribine Tablets on the PK of a Monophasic Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel (Microgynon®) in Pre-Menopausal Women With RMS
ClinicalTrials.gov ID: NCT03745144
Acronym / sponsor ID: MS700568_0031
Conditions: Relapsing Multiple Sclerosis (RMS)
Keywords: Multiple Sclerosis, Cladribine, Microgynon®
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 17 Jan 2019 (actual)
Primary completion: 2 Sep 2022 (actual)
Study completion: 16 Sep 2022 (actual)
First posted: 19 Nov 2018 (actual)
Results: Posted 15 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Sequence 1: First Cladribine, Then Placebo	Experimental	Drug: Cladribine, Drug: Placebo, Drug: Microgynon®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	Experimental	Drug: Cladribine, Drug: Placebo, Drug: Microgynon®Participants 5-day once daily 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.
Microgynon®	Experimental	Drug: Microgynon®Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle.

Who may qualify

Ages: 18 to 45 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Are pre-menopausal women with or without child-bearing potential with a negative serum pregnancy test, and women with child-bearing potential receiving adequate birth control
Participants with diagnosis of clinically stable and definite relapsing multiple sclerosis (RMS)
Adequate hematological, hepatic and renal function as defined in the protocol
Are able and willing to accept dietary restrictions and restrictions regarding the use of concomitant medications (including over-the-counter products, herbal medicines and dietary supplements) over the course of the study
Had a body weight and body mass index (BMI) within the range at screening

Key exclusion criteria (8 listed)

History of clinically relevant allergy or known hypersensitivity to the active substance or to any of the excipients of cladribine tablets or hypersensitivity to drugs with a similar chemical structure to cladribine - History of clinically relevant allergy or known hypersensitivity to 1 of the active substances levonorgestrel (LNG) or ethinylestradiol (EE) or to any excipients of Microgynon® tablets
Positive results from serology examination for Hepatitis B surface antigen (HbsAg) not due to vaccination, hepatitis B core antibody (HbcAb), Hepatitis C virus antibody (anti- HCV) or Human Immunodeficiency antibody (anti-HIV)
Presence or risk of venous thromboembolism (VTE) arterial thromboembolism (ATE)
Diabetes mellitus (Type 1 or Type 2) with vascular manifestations
Signs or symptoms of neurological disease other than multiple sclerosis (MS) that could explain the symptoms of the participant

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CladribineParticipants received cladribine once-daily for 5 consecutive days in treatment period 1 and 2.	Drug	Sequence 1: First Cladribine, Then Placebo, Sequence 2: First Placebo, Then Cladribine
PlaceboParticipants received placebo matched to cladribine once-daily for 5 consecutive days in treatment period 1 and 2.	Drug	Sequence 1: First Cladribine, Then Placebo, Sequence 2: First Placebo, Then Cladribine
Microgynon®Participants received Microgynon® tablet once daily for 21 days in treatment period 1 and 2. Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle in Run-in period.	Drug	Microgynon®, Sequence 1: First Cladribine, Then Placebo, Sequence 2: First Placebo, Then Cladribine

Primary outcome

Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
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.
Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Maximum observed plasma concentration in steady state (Cmax,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.
Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Minimum observed plasma concentration in steady state (Cmin,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Plasma concentration at end of dosing interval at steady state (Ctrough) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.
Time to Reach the Maximum Observed Plasma Concentration At Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Time to reach the maximum observed plasma concentration at steady state (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel were reported. Calculated using descriptive statistics.
Average Plasma Concentration at Steady State (Cav,ss) of Ethinyl Estradiol and Levonorgestrel
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
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.
Peak-to-Trough Fluctuation Over One Complete Dosing Interval At Steady State (PTF%)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
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.

6 secondary outcomes

Number of Participants With Treatment -Emergent Adverse Events (TEAEs)
Time frame: Up to Day 84
Number of Participants With Clinically Relevant Change From Baseline in Laboratory Values
Time frame: Up to Day 84
Number of Participants With Clinically Relevant Change From Baseline in Electrocardiogram (ECG)
Time frame: Up to Day 84
Number of Participants With Clinically Relevant Change From Baseline in Vital Signs
Time frame: Up to Day 84
Maximum Plasma Concentration (Cmax) of Cladribine
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13

Results and safety

Results posted to the registry on 15 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Microgynon®	28	24
Sequence 1: First Cladribine, Then Placebo	0	0
Sequence 2: First Placebo, Then Cladribine	0	0

Primary outcome: Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14. Geometric mean (Geometric Coefficient of Variation). Unit: hour*picograms per millilitre(h*pg/ml)

Measure	Microgynon + Cladribine n = 21	Microgynon + Placebo n = 21
Ethinyl Estradiol	789 (56.9)	817 (52.6)
Levonorgestrel	91400 (45.2)	92000 (46.8)

Population analysed: 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).

Primary outcome: Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14. Geometric mean (Geometric Coefficient of Variation). Unit: pg/ml

Measure	Microgynon + Cladribine n = 21	Microgynon + Placebo n = 21
Ethinyl Estradiol	88.3 (46.5)	88.1 (45.7)
Levonorgestrel	7950 (33.9)	8150 (34.6)

Primary outcome: Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14. Geometric mean (Geometric Coefficient of Variation). Unit: pg/ml

Measure	Microgynon + Cladribine n = 21	Microgynon + Placebo n = 21
Ethinyl Estradiol	14.8 (66.3)	14.7 (65.6)
Levonorgestrel	2520 (49.5)	2430 (56.3)

Primary outcome: Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel

Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14. Geometric mean (Geometric Coefficient of Variation). Unit: pg/ml

Measure	Microgynon + Cladribine n = 21	Microgynon + Placebo n = 21
Ethinyl Estradiol	15.5 (66.8)	15.4 (66.9)
Levonorgestrel	2580 (48.5)	2580 (56.0)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 84. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Run-in Period: Microgynon (Day -28 to -1)	0 of 28 (0%)	7 of 28 (25%)	0 of 28
Sequence 1 Period 1: Microgynon Alone (Day 1-8)	0 of 13 (0%)	3 of 13 (23.1%)	0 of 13
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)	0 of 13 (0%)	9 of 13 (69.2%)	0 of 13
Sequence 1 Period 2: Microgynon Alone (Day 1-8)	0 of 13 (0%)	5 of 13 (38.5%)	0 of 13
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)	0 of 13 (0%)	5 of 13 (38.5%)	0 of 13
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)	0 of 13 (0%)	4 of 13 (30.8%)	0 of 13
Sequence 2 Period 1: Microgynon Alone (Day 1-8)	0 of 11 (0%)	1 of 11 (9.1%)	0 of 11
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)	0 of 10 (0%)	5 of 10 (50%)	0 of 10
Sequence 2 Period 2: Microgynon Alone (Day 1-8)	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)	0 of 10 (0%)	7 of 10 (70%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Trial Awareness and Transparency websiteLink provided by the sponsor.
Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
Individual participant dataSharing planned: No. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

Merck KGaA, Darmstadt, Germany

7 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cladribine and Microgynon® in people with Relapsing Multiple Sclerosis (RMS), run by Merck KGaA, Darmstadt, Germany at 7 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Poland, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel (time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03745144.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.