Drug-drug Interaction Between Rifampicin and Progestins/Ethinylestradiol and Midazolam

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Bayer

Status and phase

Completed
Phase 1

Conditions

Biological Availability

Treatments

Drug: Norethindrone/ Noriday
Drug: Desogestrel/ Cerazette
Drug: Drospirenone, Ethinylestradiol/ Yasmin
Drug: Rifampicin
Drug: levonorgestrel/ Microlut
Drug: Midazolam/ Midazolam-ratiopharm
Drug: Dienogest/ Visanne

Study type

Interventional

Funder types

Industry

Identifiers

NCT03353857
19604
2017-002792-26 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

68 patients

Sex

Female

Ages

45 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • 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)

Exclusion criteria

  • 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 design

Primary purpose

Other

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

68 participants in 5 patient groups

levonorgestrel
Experimental group
Description:
levonorgestrel and midazolam will be administered on Day 1, Day 15 and Day 26. rifampicin (10 mg/day) will be administered on Day 8 to Day 18 and rifampicin (600 mg/day) on Day 19 to Day 29.
Treatment:
Drug: Midazolam/ Midazolam-ratiopharm
Drug: levonorgestrel/ Microlut
Drug: Rifampicin
norethindrone
Experimental group
Description:
norethindrone and midazolam will be administered on Day 1, Day 15 and Day 26. rifampicin (10 mg/day) will be administered on Day 8 to Day 18 and rifampicin (600 mg/day) on Day 19 to Day 29.
Treatment:
Drug: Midazolam/ Midazolam-ratiopharm
Drug: Rifampicin
Drug: Norethindrone/ Noriday
desogestrel
Experimental group
Description:
desogestrel and midazolam will be administered on Day 1, Day 15 and Day 26. rifampicin (10 mg/day) will be administered on Day 8 to Day 18 and rifampicin (600 mg/day) on Day 19 to Day 29.
Treatment:
Drug: Midazolam/ Midazolam-ratiopharm
Drug: Rifampicin
Drug: Desogestrel/ Cerazette
dienogest
Experimental group
Description:
dienogest and midazolam will be administered on Day 1, Day 15 and Day 26. rifampicin (10 mg/day) will be administered on Day 8 to Day 18 and rifampicin (600 mg/day) on Day 19 to Day 29.
Treatment:
Drug: Dienogest/ Visanne
Drug: Midazolam/ Midazolam-ratiopharm
Drug: Rifampicin
Drospirenone/ ethinylestradiol
Experimental group
Description:
drospirenone/ethinylestradiol and midazolam will be administered on Day 1, Day 15 and Day 26. rifampicin (10 mg/day) will be administered on Day 8 to Day 18 and rifampicin (600 mg/day) on Day 19 to Day 29.
Treatment:
Drug: Midazolam/ Midazolam-ratiopharm
Drug: Rifampicin
Drug: Drospirenone, Ethinylestradiol/ Yasmin

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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