check_circleStudy Completed

Biological availability

Bayer Identifier:

19604

ClinicalTrials.gov Identifier:

NCT03353857

EudraCT Number:

2017-002792-26

EU CT Number:

Not Available
Drug-drug interaction between rifampicin and progestins/ethinylestradiol and midazolam

Trial purpose

Quantify the effect of a probe CYP3A4 inducer (Rifampicin) on the pharmacokinetics of levonorgestrel, norethindrone, desogestrel, dienogest, drospirenone,estradiol and midazolam

Key Participants Requirements

Sex

Female

Age

45 - 70 Years
  • - Healthy female subject based on a complete medical history, physical examination, ECG, and clinical laboratory tests
    - Age: 45 to 70 years (inclusive) at the first screening visit
    - Minimum body weight 50 kg with Body mass index (BMI) above or equal to 18.5 kg/m², and below or equal to 30 kg/m² at the first screening visit
    - Postmenopausal state, revealed indicated by either:
     -- medical history, if applicable (natural menopause at least 12 months prior to first study drug administration, for women younger than 60 years confirmed by follicle stimulating hormone (FSH) >40 IU/L AND estradiol ≤ 20 pg/mL; or
     -- surgical menopause by bilateral ovariectomy at least 3 months prior to first study drug administration)

  • - Relevant diseases within the last 4 weeks prior to the first study drug administration, i.e. any disease requiring treatment by a health-care provider
    - Febrile illness within 1 week before the first study drug administration
    - Known severe allergies, non-allergic drug reactions, or multiple drug allergies
    - Presence or history of thrombosis, thrombophlebitis, thromboembolic diseases of veins and/or arteries, e.g. deep vein thrombosis, stroke, myocardial infarction, pulmonary embolism, transient ischemic attack, angina pectoris
    - Presence or history of conditions that increase the risk of thromboembolic diseases, e.g. disturbances of the coagulation system, thromboembolic diseases in close relatives at age ≤50 years], valvular heart disease, atrial fibrillation, cardiac dysfunction)
    - Presence, history, or suspected presence of malignant tumors or tumors of the liver and pituitary
    - Presence or history of liver disease e.g. disturbances of the bilirubin excretion (Dubin-Johnson and Rotor syndromes), cholecystectomy ; cholestasis, idiopathic icterus or pruritus during a previous pregnancy or estrogen-progestogen treatment
    - Relevant kidney diseases or renal injury associated with multisystem diseases/disorders, e.g. glomerulonephritis systemic lupus erythematous, diabetic nephropathy. A history of a single episode of uncomplicated nephrolithiasis does not prevent participation
    - Known metabolic disorder, e.g. diabetes mellitus, severe hypertriglyceridemia
    - Migraine with neurologic symptoms
    - Clinically significant depression, current or in the last year
    - Known current thyroid disorders which require treatment. Subjects with an euthyroid struma who do not need any treatment can participate.
    - Chronic respiratory insufficiency
    - History of porphyria
    - Contraindications for midazolam, e.g. myasthenia gravis, and sleep apnea

Trial summary

Enrollment Goal
68
Trial Dates
November 2017 - February 2019
Phase
Phase 1
Could I Receive a placebo
No
Products
BAY1902607
Accepts Healthy Volunteer
Yes

Where to participate

StatusInstitutionLocation
Completed
CRS Clinical-Research-Services Mönchengladbach GmbHMönchengladbach, 41061, Germany
Completed
CRS Clinical-Research-Services Mannheim GmbHMannheim, 68167, Germany

Primary Outcome

  • Area under the plasma concentration time curve from zero to infinity (AUC) of levonorgestrel in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of levonorgestrel in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Area under the plasma concentration time curve from zero to infinity (AUC) of norethindrone in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of norethindrone in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Area under the plasma concentration time curve from zero to infinity (AUC) of etonogestrel in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of etonogestrel in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Area under the plasma concentration time curve from zero to infinity (AUC) of dienogest in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of dienogest in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Area under the plasma concentration time curve from zero to infinity (AUC) of drospirenone (+EE) in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of drospirenone (+EE) in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Area under the plasma concentration time curve from zero to infinity (AUC) of ethinylestradiol (+DRSP) in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of ethinylestradiol (+DRSP) in the presence of MDZ (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Area under the plasma concentration time curve from zero to infinity (AUC) of midazolam in combination with the hormonal contraceptive only (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3
  • Maximum plasma concentration (Cmax) of midazolam in combination with the hormonal contraceptive only (without RIF) and in combination with 10 mg/d and 600 mg/d RIF
    date_rangeTime Frame:
    Over 7 days in Period 1 (no RIF) and 4 days in treatment Periods 2 and 3

Trial design

Open-label, randomized, fixed sequence cross-over study with five parallel treatment arms and three treatment periods to quantify the drug-drug interactions of two rifampicin dose strengths on four progestins and a fixed progestin-ethinylestradiol combination compared with midazolam in healthy post-menopausal women
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Other
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
5

Additional Information

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