Effects of Cladribine Tablets on the PK of Microgynon®

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

CompletedPhase 1Relapsing MSNCT03745144

What it found

Results posted, not judged

Results are posted in the registry, but without a statistical test of the main measure. See the numbers below.

What was tested

Treatment tested

Placebo

  • Placebo

Results by group

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine789 hour*picograms per millilitre(h*pg/ml)56.9 (Geometric Coefficient of Variation)21
Microgynon + Placebo817 hour*picograms per millilitre(h*pg/ml)52.6 (Geometric Coefficient of Variation)21
Microgynon + Cladribine91400 hour*picograms per millilitre(h*pg/ml)45.2 (Geometric Coefficient of Variation)21
Microgynon + Placebo92000 hour*picograms per millilitre(h*pg/ml)46.8 (Geometric Coefficient of Variation)21

Microgynon + Cladribine

789

Microgynon + Placebo

817

Microgynon + Cladribine

91400

Microgynon + Placebo

92000

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine88.3 pg/ml46.5 (Geometric Coefficient of Variation)21
Microgynon + Placebo88.1 pg/ml45.7 (Geometric Coefficient of Variation)21
Microgynon + Cladribine7950 pg/ml33.9 (Geometric Coefficient of Variation)21
Microgynon + Placebo8150 pg/ml34.6 (Geometric Coefficient of Variation)21

Microgynon + Cladribine

88.3

Microgynon + Placebo

88.1

Microgynon + Cladribine

7950

Microgynon + Placebo

8150

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine14.8 pg/ml66.3 (Geometric Coefficient of Variation)21
Microgynon + Placebo14.7 pg/ml65.6 (Geometric Coefficient of Variation)21
Microgynon + Cladribine2520 pg/ml49.5 (Geometric Coefficient of Variation)21
Microgynon + Placebo2430 pg/ml56.3 (Geometric Coefficient of Variation)21

Microgynon + Cladribine

14.8

Microgynon + Placebo

14.7

Microgynon + Cladribine

2520

Microgynon + Placebo

2430

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine15.5 pg/ml66.8 (Geometric Coefficient of Variation)21
Microgynon + Placebo15.4 pg/ml66.9 (Geometric Coefficient of Variation)21
Microgynon + Cladribine2580 pg/ml48.5 (Geometric Coefficient of Variation)21
Microgynon + Placebo2580 pg/ml56 (Geometric Coefficient of Variation)21

Microgynon + Cladribine

15.5

Microgynon + Placebo

15.4

Microgynon + Cladribine

2580

Microgynon + Placebo

2580

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine1.00 hours0–221
Microgynon + Placebo1.00 hours0.417–221
Microgynon + Cladribine1.00 hours0.417–221
Microgynon + Placebo1.00 hours0.417–221

Microgynon + Cladribine

1

Microgynon + Placebo

1

Microgynon + Cladribine

1

Microgynon + Placebo

1

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine32.9 pg/ml56.9 (Geometric Coefficient of Variation)21
Microgynon + Placebo34.1 pg/ml52.6 (Geometric Coefficient of Variation)21
Microgynon + Cladribine3810 pg/ml45.2 (Geometric Coefficient of Variation)21
Microgynon + Placebo3830 pg/ml46.8 (Geometric Coefficient of Variation)21

Microgynon + Cladribine

32.9

Microgynon + Placebo

34.1

Microgynon + Cladribine

3810

Microgynon + Placebo

3830

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

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

GroupValueIntervalNumber analysed
Microgynon + Cladribine220 percentage fluctuation28 (Geometric Coefficient of Variation)21
Microgynon + Placebo213 percentage fluctuation23.2 (Geometric Coefficient of Variation)21
Microgynon + Cladribine140 percentage fluctuation29.7 (Geometric Coefficient of Variation)21
Microgynon + Placebo145 percentage fluctuation29 (Geometric Coefficient of Variation)21

Microgynon + Cladribine

220

Microgynon + Placebo

213

Microgynon + Cladribine

140

Microgynon + Placebo

145

Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.

Safety

GroupParticipants at riskSerious adverse eventsDeaths
Run-in Period: Microgynon (Day -28 to -1)280 (0.0%)0
Sequence 1 Period 1: Microgynon Alone (Day 1-8)130 (0.0%)0
Sequence 1 Period 1: Microgynon + Cladribine (Day 9-28)130 (0.0%)0
Sequence 1 Period 2: Microgynon Alone (Day 1-8)130 (0.0%)0
Sequence 1 Period 2: Microgynon + Placebo (Day 9-14)130 (0.0%)0
Sequence 1 Period 2: Microgynon + Cladribine (Day 15-28)130 (0.0%)0
Sequence 2 Period 1: Microgynon Alone (Day 1-8)110 (0.0%)0
Sequence 2 Period 1: Microgynon + Placebo (Day 9-28)100 (0.0%)0
Sequence 2 Period 2: Microgynon Alone (Day 1-8)100 (0.0%)0
Sequence 2 Period 2: Microgynon + Cladribine (Day 9-28)100 (0.0%)0

As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.

What it measured

Main measures

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

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

    How the body handles the medicine

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

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

    How the body handles the medicine

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

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

    How the body handles the medicine

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

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

    How the body handles the medicine

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

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

    How the body handles the medicine

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

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

    How the body handles the medicine

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

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

    How the body handles the medicine

Other measures (6)

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

    Up to Day 84

    Safety

  • 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

    Safety

  • 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

    How the body handles the medicine

  • Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cladribine

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

    How the body handles the medicine

Who could take part

Relapsing MS · 18 to 45

Show the full 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 * Had 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

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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).

Papers

Loading reviews and guidelines…

Related trials

History

    1. Started

      Jan 2019

    2. Main results due

      Sept 2022

    3. Finished

      Sept 2022

    4. Results posted

      Mar 2024

    Assembled by software from public sources.