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

NCT ID: NCT03353857

Last Updated: 2020-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-29

Study Completion Date

2019-02-19

Brief Summary

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

Detailed Description

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Conditions

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Biological Availability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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levonorgestrel

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.

Group Type EXPERIMENTAL

levonorgestrel/ Microlut

Intervention Type DRUG

In Period 1, 0.03 mg single dose administered as 1x0.03 mg tablet on Study Day 1, In Period 2, 0.03 mg single dose administered as 1x0.03 mg tablet on Study Day 15 In Period 3, 0.03 mg single dose administered as 1x0.03 mg tablet at Study Day 26

Midazolam/ Midazolam-ratiopharm

Intervention Type DRUG

In Period 1, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 1, In Period 2, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 15 In Period 3, 1 mg single dose administered as 1x0.5 ml oral solution at Study Day 26

Rifampicin

Intervention Type DRUG

In period 2, 10 mg (suspension, 0.5 ml) for 11 days at 10 mg/day In period 3, 600 mg (film-coated tablets) for 11 days at 600 mg/day

norethindrone

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.

Group Type EXPERIMENTAL

Norethindrone/ Noriday

Intervention Type DRUG

In Period 1, 0.35 mg single dose administered as 1x0.35 mg tablet on Study Day 1, In Period 2, 0.35 mg single dose administered as 1x0.35 mg tablet on Study Day 15 In Period 3, 0.35 mg single dose administered as 1x0.35 mg tablet at Study Day 26

Midazolam/ Midazolam-ratiopharm

Intervention Type DRUG

In Period 1, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 1, In Period 2, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 15 In Period 3, 1 mg single dose administered as 1x0.5 ml oral solution at Study Day 26

Rifampicin

Intervention Type DRUG

In period 2, 10 mg (suspension, 0.5 ml) for 11 days at 10 mg/day In period 3, 600 mg (film-coated tablets) for 11 days at 600 mg/day

desogestrel

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.

Group Type EXPERIMENTAL

Desogestrel/ Cerazette

Intervention Type DRUG

In Period 1, 0.075 mg single dose administered as 1x0.075 mg tablet on Study Day 1, In Period 2, 0.075 mg single dose administered as 1x0.075 mg tablet on Study Day 15 In Period 3, 0.075 mg single dose administered as 1x0.075 mg tablet at Study Day 26

Midazolam/ Midazolam-ratiopharm

Intervention Type DRUG

In Period 1, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 1, In Period 2, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 15 In Period 3, 1 mg single dose administered as 1x0.5 ml oral solution at Study Day 26

Rifampicin

Intervention Type DRUG

In period 2, 10 mg (suspension, 0.5 ml) for 11 days at 10 mg/day In period 3, 600 mg (film-coated tablets) for 11 days at 600 mg/day

dienogest

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.

Group Type EXPERIMENTAL

Dienogest/ Visanne

Intervention Type DRUG

In Period 1, 2 mg single dose administered as 1x2 mg tablet on Study Day 1, In Period 2, 2 mg single dose administered as 1x2 mg tablet on Study Day 15 In Period 3, 2 mg single dose administered as 1x2 mg tablet at Study Day 26

Midazolam/ Midazolam-ratiopharm

Intervention Type DRUG

In Period 1, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 1, In Period 2, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 15 In Period 3, 1 mg single dose administered as 1x0.5 ml oral solution at Study Day 26

Rifampicin

Intervention Type DRUG

In period 2, 10 mg (suspension, 0.5 ml) for 11 days at 10 mg/day In period 3, 600 mg (film-coated tablets) for 11 days at 600 mg/day

Drospirenone/ ethinylestradiol

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.

Group Type EXPERIMENTAL

Drospirenone, Ethinylestradiol/ Yasmin

Intervention Type DRUG

In Period 1, 3 mg drospirenone, 0.03 mg ethinylestradiol single dose administered as 1x3mg drospirenone, 0.03 mg ethinylestradiol tablet on Study Day 1, In Period 2, 3 mg drospirenone, 0.03 mg ethinylestradiol single dose administered as 1x3mg drospirenone, 0.03 mg ethinylestradiol tablet on Study Day 15, In Period 3, 3 mg drospirenone, 0.03 mg ethinylestradiol single dose administered as 1x3mg drospirenone, 0.03 mg ethinylestradiol tablet on Study Day 26,

Midazolam/ Midazolam-ratiopharm

Intervention Type DRUG

In Period 1, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 1, In Period 2, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 15 In Period 3, 1 mg single dose administered as 1x0.5 ml oral solution at Study Day 26

Rifampicin

Intervention Type DRUG

In period 2, 10 mg (suspension, 0.5 ml) for 11 days at 10 mg/day In period 3, 600 mg (film-coated tablets) for 11 days at 600 mg/day

Interventions

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levonorgestrel/ Microlut

In Period 1, 0.03 mg single dose administered as 1x0.03 mg tablet on Study Day 1, In Period 2, 0.03 mg single dose administered as 1x0.03 mg tablet on Study Day 15 In Period 3, 0.03 mg single dose administered as 1x0.03 mg tablet at Study Day 26

Intervention Type DRUG

Norethindrone/ Noriday

In Period 1, 0.35 mg single dose administered as 1x0.35 mg tablet on Study Day 1, In Period 2, 0.35 mg single dose administered as 1x0.35 mg tablet on Study Day 15 In Period 3, 0.35 mg single dose administered as 1x0.35 mg tablet at Study Day 26

Intervention Type DRUG

Desogestrel/ Cerazette

In Period 1, 0.075 mg single dose administered as 1x0.075 mg tablet on Study Day 1, In Period 2, 0.075 mg single dose administered as 1x0.075 mg tablet on Study Day 15 In Period 3, 0.075 mg single dose administered as 1x0.075 mg tablet at Study Day 26

Intervention Type DRUG

Dienogest/ Visanne

In Period 1, 2 mg single dose administered as 1x2 mg tablet on Study Day 1, In Period 2, 2 mg single dose administered as 1x2 mg tablet on Study Day 15 In Period 3, 2 mg single dose administered as 1x2 mg tablet at Study Day 26

Intervention Type DRUG

Drospirenone, Ethinylestradiol/ Yasmin

In Period 1, 3 mg drospirenone, 0.03 mg ethinylestradiol single dose administered as 1x3mg drospirenone, 0.03 mg ethinylestradiol tablet on Study Day 1, In Period 2, 3 mg drospirenone, 0.03 mg ethinylestradiol single dose administered as 1x3mg drospirenone, 0.03 mg ethinylestradiol tablet on Study Day 15, In Period 3, 3 mg drospirenone, 0.03 mg ethinylestradiol single dose administered as 1x3mg drospirenone, 0.03 mg ethinylestradiol tablet on Study Day 26,

Intervention Type DRUG

Midazolam/ Midazolam-ratiopharm

In Period 1, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 1, In Period 2, 1 mg single dose administered as 1x0.5 ml oral solution on Study Day 15 In Period 3, 1 mg single dose administered as 1x0.5 ml oral solution at Study Day 26

Intervention Type DRUG

Rifampicin

In period 2, 10 mg (suspension, 0.5 ml) for 11 days at 10 mg/day In period 3, 600 mg (film-coated tablets) for 11 days at 600 mg/day

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

45 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CRS Clinical-Research-Services Mannheim GmbH

Mannheim, Baden-Wurttemberg, Germany

Site Status

CRS Clinical-Research-Services Mönchengladbach GmbH

Mönchengladbach, North Rhine-Westphalia, Germany

Site Status

Countries

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Germany

Related Links

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http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

https://clinicaltrials.bayer.com/

Click here to find results for studies related to Bayer Healthcare products.

Other Identifiers

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2017-002792-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

19604

Identifier Type: -

Identifier Source: org_study_id

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