Clinical trial NCT03745144: Effects of Cladribine Tablets on the PK of Microgynon®
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsing Multiple Sclerosis (RMS)
Keywords: Multiple Sclerosis
Cladribine
Microgynon®
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-11-19
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
measure: Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
measure: Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
measure: Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
measure: Time to Reach the Maximum Observed Plasma Concentration At Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
measure: Average Plasma Concentration at Steady State (Cav,ss) of Ethinyl Estradiol and Levonorgestrel
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
measure: Peak-to-Trough Fluctuation Over One Complete Dosing Interval At Steady State (PTF%)
timeFrame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14
Secondary outcomes:
measure: Number of Participants With Treatment -Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 84
measure: Number of Participants With Clinically Relevant Change From Baseline in Laboratory Values
timeFrame: Up to Day 84
measure: Number of Participants With Clinically Relevant Change From Baseline in Electrocardiogram (ECG)
timeFrame: Up to Day 84
measure: Number of Participants With Clinically Relevant Change From Baseline in Vital Signs
timeFrame: Up to Day 84
measure: Maximum Plasma Concentration (Cmax) of Cladribine
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: St. Josef und St. Elisabeth Hospital gGmbH
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
city: Katowice
country: Poland
facility: M.A. - LEK A.M.Maciejowscy SC.
city: Nadarzyn
country: Poland
facility: BioResearch Group Sp. z o. o
city: Nałęczów
country: Poland
facility: IKARDIA Hospital Cardiology
city: Otwock
country: Poland
facility: BioVirtus Research Site Sp
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: