Healthy volunteers
Conditions
Interventions
Product Name: AEB071
Product Code: AEB071
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not established
CAS Number: 425637-18-9
Current Sponsor code: AEB071 drug substance, mono acetate
Othe
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Healthy, male or female subjects, 18 to 45 years of age having provided written informed consent before entering the study. Only non-smokers will be eligible. Smokers will be defined as any subject who reports cigarette use or has a urine cotinine greater than 500 ng/mL. • Subjects must have a body weight between 50 and 90 kg and a BMI between 18-28 kg/m2. • Female subjects must be post menopausal or surgically sterilized 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Presence and/or history of a clinically significant illness in the two weeks prior to dosing, history of drug or alcohol abuse, use of any prescription drug or over-the-counter (OTC) medication (acetaminophen is acceptable) or herbal products in the 14 days prior to dosing. • A marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration of a QTcF interval >500); • A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome); • Presence of clinically significant illness, active infectious process (viral or bacterial) including (but not limited to) history of herpetic infections, positive tuberculosis tests, other infections at risk of relapse or documented drug allergies that may affect the subject’s safety during the study. • Laboratory or clinical evidence suggestive of liver or renal disease, history of heart disease, history of autonomic dysfunction (e.g. history of fainting, orthostatic hypotension, sinus arrhythmia), history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated), history major gastrointestinal disease, history or clinical evidence of pancreatic injury or pancreatitis. • Subjects with a resting heart rate 90 bpm • Subjects with systolic blood pressure < 90 or diastolic blood pressure < 50 mmHg. • Subjects with lymphocyte counts less than 1000/mm3 or total WBC greater than 11000/mm3 at baseline • Subject who intend to or have received any live attenuated vaccines 4 weeks prior to or during the study period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part I • To explore the tolerability and pharmacokinetics of 100 mg AEB071 in combination with ritonavir-induced CYP3A inhibition Part II • To evaluate the tolerability of super-therapeutic AEB071 exposure following a single oral dose of AEB071 administered under ritonavir-induced CYP3A inhibition. • To evaluate the pharmacokinetics of a clinically equivalent dose of AEB071 administered under ritonavir-induced CYP3A inhibition. ;Secondary Objective: • To explore the cardiovascular pharmacodynamics of high exposure AEB071 under ritonavir-induced CYP3A inhibition.;Primary end point(s): 24 subjects are needed to complete the part II with evaluable PK results. Assuming that the true treatment ratio AEB071 SD+Ritonavir/ AEB071 SD is 5, with the sample size of 24 in the cross-over study, there will be 80% power to show that the t distribution based 90% confidence interval for the true treatment ratio is within 3.45 and 7.25. With 80% probability the 90% t-based Confidence Interval of true treatment ratio should lie within 0.80- 1.25 of the estimated mean ratio. For example if the estimated mean ratio is 5 the CI based on t-statistics should be within 4.0-6.3, and if the observed ratio is 6 the CI t-statistics should be within 4.78-7.53. These calculations assume no within subject correlation and that the co-efficient of variation is 43%. | — |
Countries
France
Outcome results
None listed