A study in healthy volunteers to assess two different formulations (recipes) of the drug product (Alectinib)
- Conditions
- Cancer
- Registration Number
- ISRCTN40852430
- Lead Sponsor
- Chugai Pharmaceutical Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 32
1. Must provide written informed consent
2. Must be willing and able to communicate and participate in the whole study
3. Aged 18 to 55 years inclusive at the time of signing informed consent
4. Must agree to adhere to the contraception requirements
5. Healthy males or non-pregnant, non-lactating healthy females of non-childbearing potential
6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening
1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients
2. Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hay fever is allowed unless it is active
3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the Investigator or history of visual disturbances (e.g. blurred vision, vitreous floaters, visual impairment, reduced visual acuity, asthenopia, and diplopia) unless determined to be clinically not significant by agreement between the Investigator and the sponsor’s medical monitor
4. Subjects with a history of cholecystectomy or gall stones
5. Subjects with known deglutition/oesophageal pathology which can affect transit of food/drink, or who have any swallowing difficulties/evidence of swallowing impairment
6. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator or delegate at screening
7. Evidence of current SARS-CoV-2 infection
8. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the Investigator. Subjects will be excluded if they have ALT, AST or total bilirubin above the upper limit of the reference range or haemoglobin less than the lower limit of the reference range, neutrophil or lymphocyte count below the lower limit of normal or creatine kinase 1.25 × the upper limit of the reference range without an alternative explanation (e.g. physical activity)
9. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results
10. Evidence of renal impairment at screening, as indicated by an eGFR of <80 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; 2009) equation or any other evidence of renal impairment
11. Subjects with a resting heart rate of <50 beats per min as determined by a mean of triplicate ECG or vital signs measurement at screening or as a mean of triplicate ECG at baseline measurement on pre-dose Day 1 of Period 1 for each study part (mean of triplicate ECG observation for ventricular rate will take precedence over heart rate as measured by vital signs assessment if there is a discord)
12. Clinically significant findings on ECG including but not limited to prolonged QTcF, second degree heart block or greater
13. Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative highly sensitive serum pregnancy test at screening and urine at all other time points). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration =40 IU/L)
14. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer
15. Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood
16. Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day, HRT or hormonal contraception) in the 14 days before
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Relative bioavailability (Frel) for Cmax, AUC(0-last) and AUC(0-inf) of alectinib, its M4 metabolite and total exposure (alectinib + M4) in plasma, measured using blood samples at pre-dose and multiple timepoints up to 72 h post-dose
- Secondary Outcome Measures
Name Time Method 1. PK parameters where appropriate, including but not limited to: Tmax, Cmax, AUC(0-last), AUC(0-inf), T1/2 and metabolite parent ratios for alectinib, its M4 metabolite and total exposure (alectinib + M4) in plasma, measured using blood samples at pre-dose and multiple timepoints up to 72 h post-dose<br>2. Incidence of adverse events (AEs) and change from baseline for vital signs, electrocardiograms (ECGs), physical examinations and laboratory safety tests, from the time of signing the informed consent form up until the follow-up visit (7 to 10 days post-final dose)