Effects of Cladribine Tablets on the PK of Microgynon®

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Relapsing Multiple Sclerosis (RMS)

Treatments: Drug: Placebo; Drug: Microgynon®; Drug: Cladribine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03745144

2018-001015-70 (EudraCT Number)

MS700568_0031

Details and patient eligibility

About

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).

Enrollment: 28 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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28 participants in 3 patient groups

Sequence 1: First Cladribine, Then Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Cladribine

Drug: Microgynon®

Sequence 2: First Placebo, Then Cladribine

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Cladribine

Drug: Microgynon®

Microgynon®

Experimental group

Description:

Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle.

Treatment:

Drug: Microgynon®