Safety, tolerability and clinical activity of fenebrutinib in healthy subjects Other
Conditions
Interventions
Part A: Single Ascending Dose Study
Participants will enroll in three sequential cohorts (A1, A2, and A3) that will test single ascending doses. In cohort A1, participants will receive a single dose o
the dose will be determined based on analysis of the data from the prior cohort.
Duration: 1 day of treatment, 7 days of follow-up.
Part B: Thorough QT Interval Study
The fenebrutinib therapeutic do
Sponsors
Roche (United States)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Males or females of non-childbearing potential, between 18 and 60 years of age, inclusive; 2. Within body mass index (BMI) range 18 to 31 kg/m², inclusive, with a bodyweight >45 kg; 3. In good health, determined by no clinically significant findings from medical history, 12-lead ECG, and vital signs; 4. Clinical laboratory evaluations (including chemistry panel [fasted at least 10 hours], complete blood count [CBC], coagulation [prothrombin time {PT}, international normalized ratio {INR}, and activated partial thromboplastin time {aPTT}], and urinalysis [UA] with complete microscopic analysis) within the reference range for the test laboratory, unless deemed not clinically significant by the investigator; 5. Negative test for selected drugs of abuse and cotinine at Screening (does not include alcohol) and at Check-in (Day -1 for Part A, Period 1 Day -1 for Part B; does include alcohol); 6. Negative hepatitis panel (hepatitis B virus core antibody, hepatitis B surface antigen, and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens; 7. Females will not be pregnant or breastfeeding, and must be either postmenopausal (at least 12 months without a period [i.e., amenorrhea]; in a woman at least 50 years of age and documented by a serum follicle-stimulating hormone [FSH] level consistent with postmenopausal status [i.e., =40 IU/L] in the absence of a reversible medical iatrogenic cause) or surgically sterile (e.g., tubal ligation, bilateral salpingectomy, or hysterectomy) for at least 90 days. For all females, the pregnancy test result must be negative at Screening and Check-in (Day -1 for Part A, Period 1 Day -1 for Part B). 8. Males with partners of childbearing potential will either be sterile (confirmed by documentation in addition to agreeing to using a condom from Check-in [Day -1 for Part A, Period 1 Day -1 for Part B] until 90 days following study completion) or agree to use from Check-in (Day -1 for Part A, Period 1 Day -1 for Part B) until 90 days following study completion, one of the following approved methods of contraception: male condom with spermicide; sterile sexual partner; use by female sexual partner of an intrauterine device with spermicide; a female condom with spermicide; a contraceptive sponge with spermicide; an intravaginal system [e.g., NuvaRing®]; a diaphragm with spermicide; a cervical cap with spermicide; or oral, implantable, transdermal, or injectable contraceptives. Subjects will refrain from sperm donation from Check-in (Day -1 for Part A, Period 1 Day -1 for Part B) until 90 days or 5 half-lives plus 74 days (a spermatogenesis cycle), whichever is longer, following study completion. Male subjects (including men who have had vasectomies) whose partners are currently pregnant should use a barrier method for the duration of the study and for 90 days or 5 half-lives plus 74 days (a spermatogenesis cycle), whichever is longer, after the study completion. This is to ensure that the fetus is not exposed to the drug in the ejaculate; 9. Receive an explanation of the mandatory WGS component of the study; 10. Able to comprehend and willing to sign an Informed Consent Form (ICF); 11. Able to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the investigator) 2. Evidence of active infection (with the exception of fungal nail infections or oral herpes); history of recurrent bacterial, viral, mycobacterial, or fungal infections (defined as >2 similar episodes requiring anti-microbial treatment within the previous 12 months), with the exception of recurrent oral or genital herpes (herpes simplex virus 1/herpes simplex virus 2) or uncomplicated urinary tract infections in females; or history of infection requiring hospitalization within 8 weeks prior to Screening 3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator 4. Any personal or family history of bleeding disorders and any personal use of drugs known to affect blood clotting within 30 days prior to dosing 5. Family history of intracranial bleed (berry aneurysm, hemorrhagic stroke) or recent personal history of head trauma 6. History of vasculitis 7. Having one or more of the following clinical laboratory evaluations at Screening: • Estimated glomerular filtration rate (eGFR) 2 × ULN (may be repeated if 2 to 3 × ULN) • Total bilirubin >1.5 × ULN (may be repeated if 1.6 to 3 × ULN) • Abnormalities in hepatic synthetic function tests (e.g., PT, INR, aPTT, albumin) judged by the investigator to be clinically significant 8. Sustained (i.e., three consecutive occasions of assessments) systolic blood pressure measurements 140 mmHg or diastolic blood pressure measurements 90 mmHg at Screening 9. Sustained (i.e., confirmed upon repeat) pulse >100 or <45 beats per minute at Screening 10. Personal or family history of congenital long QT syndrome or family history of sudden death 11. History or presence of an abnormal ECG (including marked mean QTcF prolongation =450 msec) at Screening or Check-in (Day -1 for Part A, Period 1 Day -1 for Part B) that, in the investigator’s opinion, is clinically significant 12. Short QTc (mean QTcF <300 msec) at Screening or Check-in (Day -1 for Part A, Period 1 Day -1 for Part B) 13. Subject had dyspepsia for which he/she had recently taken (within 2 weeks prior to Check-in [Day -1 Part A, Period 1 Day -1 for Part B]) prescription and/or over-the-counter medicinal products for the control of gastric acidity (e.g., proton-pump inhibitors, H2 blockers, antacids) 14. History of stomach or intestinal surgery or resection or any GI disorder that would potentially alter absorption and/or excretion of orally administered drugs, except that appendectomy, hernia repair, and/or cholecystectomy will be allowed 15. History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1 for Part A, Period 1 Day -1 for Part B) 16. History of tuberculosis (TB) or treatment with TB prophylaxis within 12 months prior to study enrollment 17. Use of oral antibiotics within 4 weeks or IV antibiotics within 8 weeks prior to the Screening evaluation 18. Any vaccination within 6 weeks prior to dosing 19. Participation in any other investigational study drug trial in which receipt of an invest
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: 1. Incidence and severity of AEs and incidence of abnormalities measured using clinical laboratory evaluations, 12-lead ECGs, vital signs measurements, and physical examinations throughout the study 2. Pharmacokinetics measured using Cmax, tmax, AUC0-8 and/or AUC0-t, and t1/2 of fenebrutinib on days 1 and 2 Part B 1. Placebo-adjusted change from predose-averaged baseline QTcF (??QTcF) of fenebrutinib measured using ECG on days 1 and 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Part B: 1. Incidence and severity of AEs and incidence of abnormalities measured using clinical laboratory evaluations, 12-lead ECGs, vital signs measurements, and physical examinations throughout the study 2. Pharmacokinetics measured using Cmax, tmax, AUC0-8 and/or AUC0-t, and t1/2 of fenebrutinib and moxifloxacin on days 1 and 2 3. Absolute and change from baseline in heart rate and PR, RR, QRS, QT, and QTcB intervals; and change from baseline T-wave morphology and U-wave presence measured using ECG on days 1 and 2 4. ??QTcF of moxifloxacin measured using ... at 1, 1.5, 2, 3, and 4 hours postdose 5. Change from baseline QTcF (?QTcF) at the individual tmax for each treatment (?QTcF, tmax) measured using ECG | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed