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Effects of Cladribine Tablets on the Pharmacokinetics of Microgynon®

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ClinicalTrials.gov Identifier: NCT03745144
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Brief 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).

Condition or disease Intervention/treatment Phase
Relapsing Multiple Sclerosis (RMS) Drug: Cladribine Drug: Placebo Drug: Microgynon® Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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).
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : April 6, 2020
Estimated Study Completion Date : April 6, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Cladribine

Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. 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 ]
  2. 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 Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Occurrence of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to Day 84 ]
  9. 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.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745144


Contacts
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Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
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Germany
St. Josef und St. Elisabeth Hospital gGmbH Recruiting
Bochum, Germany, 44791
Please Contact the Merck KGaA Communication Center Recruiting
Darmstadt, Germany, 64293
Nuvisan GmbH Recruiting
Neu-Ulm, Germany, 89231
NeuroPoint Recruiting
Ulm, Germany, 89073
Fachklinik für Neurologie Dietenbronn GmbH - Diagnostisches und therapeutisches Kompetenzzentrum für Multiple Sklerose Recruiting
Ulm, Germany, 89081
Universitätsklinikum Ulm (11785) Recruiting
Ulm, Germany, 89081
Poland
BioVirtus Research Site Sp (13013) Recruiting
Otwock, Poland, 04-749
MTZ Clinical Research Sp. z o.o. Recruiting
Warszawa, Poland, 02-106
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany

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Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT03745144     History of Changes
Obsolete Identifiers: NCT04086225
Other Study ID Numbers: MS700568_0031
2018-001015-70 ( EudraCT Number )
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck KGaA, Darmstadt, Germany:
Multiple Sclerosis
Cladribine
Microgynon®
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Cladribine
Ethinyl estradiol, levonorgestrel drug combination
Ethinyl Estradiol-Norgestrel Combination
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Contraceptives, Oral, Synthetic
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital