healthy volunteers (Multiple sclerosis is the intended indication for BAF312)
Conditions
Interventions
Product Name: BAF312 0,25 mg tablet
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
CAS Number: 1234627-85-0
Current Sponsor code: BAF312
Other descriptive name: BAF312 hemifumarate
Conce
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. written IC 2. healthy females of childbearing potential 18-40 years + in good health as determined by past medical history, physical examination, vital signs, ECG, 24 h Holter and lab tests, PAP smear, gynecological exam. and transvaginal ultrasound before dosing in period 1 3. Stable regimen of monophasic OC containing EE (30 microgram)/LVG (150 microgram) as for at least three cycles prior to dosing in period 1 and willing to undergo synchronization of at least one cycle until day -7. Any subject not taking any OC or taking another brand of monophasic OC should be willing to take monophasic OC containing EE 30 microgram and LVG 150 microgram for at least three cycles during synchronization until day -7.Willing to continue OC until at least 30 d after study completion 4. negative pregnancy test results at screening and baseline 1 5. willing to use additional, non-hormonal contraception from screening until 30 days after study completion. 6. willing to undergo genotyping screening prior to baseline 1, must be CYP2C9 WT 7. willing to abstain from strenuous and/or unaccustomed physical exercise for 7 d before dosing with OC at D1 until after study completion evaluation. At screening and baseline 1, vital signs (BP and pulse rate) will be assessed in supine position after the subject has rested for at least 3 min, and again when required after 3 min in the standing pos. Investigator can be guided by: oral body temp 35-37.5°C, systolic BP 90-140 mm Hg, diastolic BP 50-90 mm Hg, pulse rate 50-90 bpm. BP and pulse after 3 min standing no more than 20 mm Hg drop systolic or 10 mm Hg drop diastolic and increase in heart rate >20 bpm (compared to sitting) associated with clin. manifestation of postural hypotension. 8. weight of at least 50 kg, BMI in the range of 18-30 kg/m2 9. abilitity to communicate well, understand and comply Other protocol defined inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. use of other investigational drugs at the time of baseline 1, or within 30 days or half-lives of baseline1, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations. 2. Hypersensitivity to study drug or drugs of similar chemical class. Bad tolerance to OCs during synchronization period 3. any contra-indication to OCs with EE/LVG 4. females who do not have had 3 consecutive menstrual cycles post partum 5. breast-feeding females or have stopped breast-feeding less than 6 mths before initial dosing 6. history of irregular menses or pregnancy while on OCs 7. current or medical history of any of following CV findings: 2nd and 3rd degree AV-block, clin. significant ECG findings, supraventricular arrhythmias, arrhythmias (e.g. Brugada syndrome, Long QT syndrome, WPW syndrome, LGL syndrome, ARVD etc.), heart failure or left ventricular dysfunction 8. history of malignancy of any organ system within 5 past years (other than localized basal cell carcinoma of skin) 9. smokers 10. use of any prescription drugs, herbal supplements within 4 wks prior to initial dosing (i.d.) (excepts monophasic OCs), and/or OTC medication, dietary supplements withing 2 wks prior i.d. 11. Donation or loss of 400 ml or more blood within 8 wks prior i.d. 12. Plasma donation within 7 d prior i.d. 13. Significant illness not resolved within 2 wks prior i.d. that may impact ADME of drugs or safety of subject 14. Recent (within last 3 y ) +/or recurrent history of autonomic dysfunction, acute or chronic bronchospastic disease (e.g. asthma and COPD) (15.) 16. medical history of any arterial disease or embolic conditions which predispose to clotting disorders or other risk factors with OC use 17. current or history of mammary or endometrial carcinoma 18. depot estrogens or progesterione injection within 10 mths prior baseline 1 19. surgical or medical condition which might significantly alter ADME of drugs or jeopardize subject: history of -inflamatory bowel disease, -ulcers, -GI or rectal bleeding, -major GI tract surgery, -pancreatic injury or pancreatitis - livery disease or liver injury and presence of abnormal liver function tests (applying criteria please see protocol) -impaired renal function as indicated (see protocol), evidence of urinary obstruction of difficulty in voiding 20. history of immunodeficiency diseases 21. positive HBsAg or Hep C test result 22. history of drug or alcohol abuse within 12 mths prior i.d 23. score 4 or 5 on the suicidal ideation items or any "yes" on the suicidal behavior item that is related to suicidal behaviour occuring during the last 2 years Other protocol defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether BAF312 administered daily at a dose of 4 mg can affect exposure (Cmax and AUC) to a daily monophasic oral contraceptive (OC) regimen containg 30 microgram ethinylestradiol (EE) and 150 microgram levonorgestrel (LVG).;Secondary Objective: To assess the effect of oral BAF312 (4 mg q.d) on the pharmacodynamics of a monophasic OC determined by Hoogland score, FSH, LH, estradiol, progesterone, SHBG concentrations and ovarian follicle size. To assess the safety and tolerabililty of oral BAF312 (4 mg q.d.) in co-administration with a monophasic OC. To assess the PK profile of oral BAF312 (4 mg q.d.) when combined with a daily administered monophasic OC regimen containing 30 microgram of EE and 150 microgram of LVG;Primary end point(s): To investigate whether BAF312 administered daily at a dose of 4 mg can affect exposure (Cmax and AUC) to a daily administered monophasic oral contraceptive (OC) regimen containing 30 µg of ethinylestradiol (EE) and 150 µg of levonorgestrel (LVG).;Timepoint(s) of evaluation of this end point: Specified on page 16/17 of the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the effect of oral BAF312 (4 mg q.d.) on the pharmacodynamics of a monophasic OC determined by Hoogland score, FSH, LH, estradiol, progesterone,SHBG concentrations and ovarian follicle size • To assess the safety and tolerability of oral BAF312 (4 mg q.d.) in co-administration with a monophasic OC, • To assess the PK profile of oral BAF312 (4 mg q.d.) when combined with a daily administered monophasic oral contraceptive (OC) regimen containing 30 µg of EE and 150 µg of LVG.;Timepoint(s) of evaluation of this end point: Specified on page 16/17 of the protocol | — |
Countries
Netherlands
Contacts
Public ContactLegal representative
Novartis Pharma Services AG
Outcome results
None listed