Clincosm LogoSign in Get a demo

Effects of Cladribine Tablets on the PK of Microgynon®

Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03745144
Collaborator
(none)
24
Enrollment
7
Locations
2
Arms
40.5
Anticipated Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
24 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 PK of a Monophasic Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel (Microgynon®) in Pre-Menopausal Women With RMS
Actual Study Start Date :
Jan 17, 2019
Anticipated Primary Completion Date :
Jun 3, 2022
Anticipated Study Completion Date :
Jun 3, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 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]

  2. 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

  1. 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]

  2. 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]

  3. 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]

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

  6. Maximum Observed Plasma Concentration (Cmax) of Cladribine [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 [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) [Up to Day 84]

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

    Number of participants with clinically significant abnormalities will be reported.

Eligibility Criteria

Criteria

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 St. Josef und St. Elisabeth Hospital gGmbH Bochum Germany
2 Nuvisan GmbH Neu-Ulm Germany
3 M.A. - LEK A.M.Maciejowscy SC. Katowice Poland
4 BioResearch Group Sp. z o. o Nadarzyn Poland
5 IKARDIA Hospital Cardiology Nałęczów Poland
6 BioVirtus Research Site Sp Otwock Poland
7 MTZ Clinical Research Sp. z o.o. Warszawa Poland

Sponsors and Collaborators

  • Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT03745144
Other Study ID Numbers:
  • MS700568_0031
  • 2018-001015-70
  • NCT04086225
First Posted:
Nov 19, 2018
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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:
Multiple Sclerosis
Sclerosis
Cladribine
Ethinyl estradiol, levonorgestrel drug combination
Ethinyl Estradiol-Norgestrel Combination

Study Results

No Results Posted as of Feb 9, 2022