Effects of Cladribine Tablets on the PK of Microgynon®

NCT03745144 | Completed Phase 1 Results

• 2 other identifiers: MS700568_00312018-001015-70
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study was 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).

Conditions

Relapsing Multiple Sclerosis (RMS)

Keywords

Multiple Sclerosis; Cladribine; Microgynon®

Outcome Measures

Primary Outcomes (7)

• Area Under the Plasma Concentration-Time Curve From Zero to Tau at Steady State (AUCt,ss) of Ethinyl Estradiol and Levonorgestrel

  Area under the plasma concentration-time curve from zero to tau at steady state (AUCt,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

• Maximum Observed Plasma Concentration in Steady State (Cmax,ss) of Ethinyl Estradiol And Levonorgestrel

  Maximum observed plasma concentration in steady state (Cmax,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated using descriptive statistics.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

• Minimum Observed Plasma Concentration in Steady State (Cmin,ss) of Ethinyl Estradiol and Levonorgestrel

  Minimum observed plasma concentration in steady state (Cmin,ss) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

• Plasma Concentration at End of Dosing Interval at Steady State (Ctrough) of Ethinyl Estradiol and Levonorgestrel

  Plasma concentration at end of dosing interval at steady state (Ctrough) of ethinyl estradiol and levonorgestrel were reported. Calculated from descriptive statistics.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

• Time to Reach the Maximum Observed Plasma Concentration At Steady State (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel

  Time to reach the maximum observed plasma concentration at steady state (Tmax,ss) of Ethinyl Estradiol and Levonorgestrel were reported. Calculated using descriptive statistics.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

• Average Plasma Concentration at Steady State (Cav,ss) of Ethinyl Estradiol and Levonorgestrel

  Average plasma concentration at steady state (Cav,ss) ) of Ethinyl Estradiol and Levonorgestrel were reported. Cav,ss =AUCt,ss/ tau, where, AUCt,ss was defined as the area under the plasma concentration-time curve in steady state during a complete dosing interval (tau) and Tau is the Complete dosing interval. Calculated using descriptive statistics.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

• Peak-to-Trough Fluctuation Over One Complete Dosing Interval At Steady State (PTF%)

  The PTF within complete dosing interval at steady state, calculated as PTF (%) = (\[Cmax - Cmin\]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.

  Pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 14

Secondary Outcomes (6)

• Number of Participants With Treatment -Emergent Adverse Events (TEAEs)

  Up to Day 84

• Number of Participants With Clinically Relevant Change From Baseline in Laboratory Values

  Up to Day 84

• Number of Participants With Clinically Relevant Change From Baseline in Electrocardiogram (ECG)

  Up to Day 84

• Number of Participants With Clinically Relevant Change From Baseline in Vital Signs

  Up to Day 84

• Maximum Plasma Concentration (Cmax) of Cladribine

  Pre-dose, 0.25, 0.5, 1, 1.5 and 2 hours post-dose on Day 10, 11, 12 and 13

Study Arms (3)

Sequence 1: First Cladribine, Then Placebo

EXPERIMENTAL

Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 milligram(mg) depending on body weight along with Microgynon® tablet once daily from Day 9-28. Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® from Day 9-14. From Day 15-28 participants received once daily Microgynon® along with 5-day once-daily Cladribine 10 to 20 mg depending on body weight.

Drug: Cladribine; Drug: Placebo; Drug: Microgynon®

Sequence 2: First Placebo, Then Cladribine

EXPERIMENTAL

Participants 5-day once daily Period 1: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine matched Placebo along with Microgynon® tablet once daily from Day 9-28. Period 2: Participants received a single once daily dose of Microgynon® tablet from Day 1-8 followed by 5-day once-daily Cladribine 10 to 20 mg depending on body weight along with Microgynon® tablet once daily from Day 9-28.

Drug: Cladribine; Drug: Placebo; Drug: Microgynon®

Microgynon®

EXPERIMENTAL

Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle.

Drug: Microgynon®

Interventions

Cladribine DRUG

Participants received cladribine once-daily for 5 consecutive days in treatment period 1 and 2.

Sequence 1: First Cladribine, Then Placebo; Sequence 2: First Placebo, Then Cladribine

Placebo DRUG

Participants received placebo matched to cladribine once-daily for 5 consecutive days in treatment period 1 and 2.

Sequence 1: First Cladribine, Then Placebo; Sequence 2: First Placebo, Then Cladribine

Microgynon® DRUG

Participants received Microgynon® tablet once daily for 21 days in treatment period 1 and 2. Participants received Microgynon® for 21 days, starting on the first day of the menstrual cycle in Run-in period.

Microgynon®; Sequence 1: First Cladribine, Then Placebo; Sequence 2: First Placebo, Then Cladribine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Had a body weight and body mass index (BMI) within the range at screening

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (7)

St. Josef und St. Elisabeth Hospital gGmbH

Bochum, Germany

Location

Nuvisan GmbH

Neu-Ulm, Germany

Location

M.A. - LEK A.M.Maciejowscy SC.

Katowice, Poland

Location

BioResearch Group Sp. z o. o

Nadarzyn, Poland

Location

IKARDIA Hospital Cardiology

Nałęczów, Poland

Location

BioVirtus Research Site Sp

Otwock, Poland

Location

MTZ Clinical Research Sp. z o.o.

Warsaw, Poland

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine; ethinyl estradiol, levonorgestrel drug combination

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49 6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: November 19, 2018
• Study Start: January 17, 2019
• Primary Completion: September 2, 2022
• Study Completion: September 16, 2022
• Last Updated: March 15, 2024
• Results First Posted: March 15, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); PL (5)