Effects of Cladribine Tablets on the Pharmacokinetics of Microgynon®

• Register: ClinicalTrials.gov
• Last refreshed on: 16 September 2019
• Main ID: NCT04086225
• Date of registration: 09/09/2019
• Prospective Registration: No
• Primary sponsor: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Public title: Effects of Cladribine Tablets on the Pharmacokinetics of Microgynon®
• Scientific 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 Pharmacokinetics of a Monophasic Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel (Microgynon®) in Pre-Menopausal Women With Relapsing Multiple Sclerosis (RMS).
• Date of first enrolment: January 17, 2019
• Target sample size: 34
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT04086225
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Other. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Germany, Poland

Contacts

• Name: Communication Center

• Name: Medical Responsible
• Affiliation: Merck KGaA, Darmstadt, Germany

Key inclusion & exclusion 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

- Have 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



Age minimum: 18 Years
Age maximum: 45 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Relapsing Multiple Sclerosis (RMS)

Intervention(s)

Drug: Cladribine

Drug: Microgynon®

Drug: Placebo

Primary Outcome(s)

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Area Under Plasma Concentration Time Curve From Zero to Tau at Steady State (AUCtau,ss) of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Secondary Outcome(s)

Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Findings [Time Frame: Up to Day 84]

Minimum Observed Plasma Concentration From Time Zero to Tau at Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Occurrence of Participants With Treatment Emergent Adverse Events (TEAEs) [Time Frame: Up to Day 84]

Peak-to-Trough Fluctuation Over One Complete Dosing Interval at Steady State of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Average Plasma Concentration at Steady State (Cave,ss) of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Maximum Observed Plasma Concentration (Cmax) of Cladribine [Time Frame: Pre-dose up to 2.0 hour post-dose on Days 10, 11, 12, and 13]

Time to Reach Maximum Observed Plasma Concentration (tmax) of Cladribine [Time Frame: Pre-dose up to 2.0 hour post-dose on Days 10, 11, 12, and 13]

Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel [Time Frame: Pre-dose up to 24 hour (Day 15) post-dose]

Secondary ID(s)

2018-001015-70

MS700568_0031

Source(s) of Monetary Support

Please refer to primary and secondary sponsors