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

• Status: Completed
• Trial end date: 2019-02-19
• Target enrollment: 0
• Participant gender: Female

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bayer
• Treatments: Desogestrel; Dienogest; Drospirenone; Drospirenone and ethinyl estradiol combination; Ethinyl Estradiol; Levonorgestrel; Midazolam; Norethindrone; Norethindrone Acetate; Progestins; Rifampin

Criteria

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