Effects of Cladribine Tablets on the Pharmacokinetics of Microgynon®

Relapsing Multiple Sclerosis (RMS) Clinical Trial

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 Pharmacokinetics of a Monophasic Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel (Microgynon®) in Pre-Menopausal Women With Relapsing Multiple Sclerosis (RMS).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04086225
• Other study ID #: MS700568_0031
• Secondary ID: 2018-001015-70
• Status: Recruiting
• Phase: Phase 1
• Start date: January 17, 2019
• Est. completion date: April 6, 2020

Study information

• Verified date: September 2019
• Source: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: Communication Center
• Phone: +49 6151 72 5200
• Email: service[@]emdgroup.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: April 6, 2020
• Est. primary completion date: April 6, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis (RMS)
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Germany	St. Josef und St. Elisabeth Hospital gGmbH	Bochum
Germany	Please Contact the Merck KGaA Communication Center	Darmstadt
Germany	Nuvisan GmbH	Neu-Ulm
Germany	Fachklinik für Neurologie Dietenbronn GmbH - Diagnostisches und therapeutisches Kompetenzzentrum für Multiple Sklerose	Ulm
Germany	NeuroPoint	Ulm
Germany	Universitätsklinikum Ulm (11785)	Ulm
Poland	BioVirtus Research Site Sp (13013)	Otwock
Poland	MTZ Clinical Research Sp. z o.o.	Warszawa

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Average Plasma Concentration at Steady State (Cave,ss) of Ethinyl Estradiol and Levonorgestrel		Pre-dose up to 24 hour (Day 15) post-dose
Secondary	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
Secondary	Maximum Observed Plasma Concentration (Cmax) of Cladribine		Pre-dose up to 2.0 hour post-dose on Days 10, 11, 12, and 13
Secondary	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
Secondary	Occurrence of Participants With Treatment Emergent Adverse Events (TEAEs)		Up to Day 84
Secondary	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