Effects of Cladribine Tablets on the PK of Microgynon®

Study Overview
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Brief Summary
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The purpose of this study is 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).

Official Title
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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
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Relapsing Multiple Sclerosis (RMS)

Intervention / Treatment
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* Drug: Cladribine
* Drug: Placebo
* Drug: Microgynon®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: First Cladribine, Then Placebo<br>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. | Drug: Cladribine<br>* Participants will receive cladribine once-daily for 5 consecutive days in treatment period 1 and 2.<br>Drug: Placebo<br>* Participants will receive placebo matched to cladribine once-daily for 5 consecutive days in treatment period 1 and 2.<br>Drug: Microgynon®<br>* Participants will receive Microgynon® tablet once daily for 21 days in treatment period 1 and 2.<br>|
| Experimental: First Placebo, Then Cladribine<br>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. | Drug: Cladribine<br>* Participants will receive cladribine once-daily for 5 consecutive days in treatment period 1 and 2.<br>Drug: Placebo<br>* Participants will receive placebo matched to cladribine once-daily for 5 consecutive days in treatment period 1 and 2.<br>Drug: Microgynon®<br>* Participants will receive Microgynon® tablet once daily for 21 days in treatment period 1 and 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Plasma Concentration Time Curve From Zero to Tau at Steady State (AUCtau,ss) of Ethinyl Estradiol and Levonorgestrel |  | Pre-dose up to 24 hour (Day 15) post-dose | 
| Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Ethinyl Estradiol and Levonorgestrel |  | Pre-dose up to 24 hour (Day 15) post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimum Observed Plasma Concentration From Time Zero to Tau at Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel |  | 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 |  | 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 |  | Pre-dose up to 24 hour (Day 15) post-dose | 
| Average Plasma Concentration at Steady State (Cave,ss) of Ethinyl Estradiol and Levonorgestrel |  | 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 |  | Pre-dose up to 24 hour (Day 15) post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of Cladribine |  | 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 |  | 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) |  | Up to Day 84 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Findings | Number of participants with clinically significant abnormalities will be reported. | Up to Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Cladribine, Microgynon®