Effects of Cladribine Tablets on the Pharmacokinetics of Microgynon®

Overview

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

Full Title of Study: “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).”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Other
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: April 6, 2020

Interventions

  • Drug: Cladribine
    • Participants will receive cladribine once-daily for 5 consecutive days in treatment period 1 and 2.
  • Drug: Placebo
    • Participants will receive placebo matched to cladribine once-daily for 5 consecutive days in treatment period 1 and 2.
  • Drug: Microgynon®
    • Participants will receive Microgynon® tablet once daily for 21 days in treatment period 1 and 2.

Arms, Groups and Cohorts

  • Experimental: First Cladribine, Then Placebo
    • Participants will receive 5-day once-daily cladribine treatment along with Microgynon® tablet once daily from Day 1 to Day 21 in period 1 followed by 5-day once daily cladribine matched placebo treatment along with Microgynon® tablet once daily from Day 1 to Day 21 in period 2.
  • Experimental: First Placebo, Then Cladribine
    • Participants 5-day once daily cladribine matched placebo treatment along with Microgynon® tablet once daily from Day 1 to Day 21 in period 1 followed by will receive 5-day once-daily cladribine treatment along with Microgynon® tablet once daily from Day 1 to Day 21 in period 2.

Clinical Trial Outcome Measures

Primary Measures

  • 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
  • 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

Secondary Measures

  • 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
  • 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
  • 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
  • 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
  • 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
  • Occurrence of Participants With Treatment Emergent Adverse Events (TEAEs)
    • Time Frame: Up to Day 84
  • Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Findings
    • Time Frame: Up to Day 84
    • Number of participants with clinically significant abnormalities will be reported.

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Merck KGaA, Darmstadt, Germany
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Responsible, Study Director, Merck KGaA, Darmstadt, Germany
  • Overall Contact(s)
    • Communication Center, +49 6151 72 5200, service@emdgroup.com

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