A study to investigate the absorption, metabolism, excretion, and bioavailability of oral and intravenous inavolisib in healthy volunteers
- Conditions
- The absorption, metabolism, excretion, and bioavailability of a PI3K inhibitor drug in healthy volunteersCancer
- Registration Number
- ISRCTN60043317
- Lead Sponsor
- Genentech, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 8
1. Males, who are sterile, and females of non-childbearing potential
2. Aged between 18 and 65 years, inclusive
3. =3 male volunteers
4. Body mass index (BMI) between 18.5 and 32.0 kg/m², inclusive
5. In good health, determined by no clinically significant findings from medical history, 12-lead ECG, vital signs, and taking no chronic medications
6. Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator. Evaluations will include a chemistry panel (fasted at least 8 h), complete blood count, coagulation testing (including prothrombin time, international normalized ratio, and activated partial thromboplastin time), and urinalysis with complete microscopic analysis, and glycosylated hemoglobin.
7. Negative test for selected drugs of abuse (does not include alcohol) at screening visit and day -1 (including alcohol)
8. Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens
9. Negative screening test for latent mycobacterium tuberculosis (TB) infection using QuantiFERON® TB Gold
10. Receive an explanation of the mandatory WGS component of the study
11. Able to comprehend and willing to sign an Informed Consent Form (ICF)
12. History of =1 bowel movement per day
13. Male volunteers: sterile by history for at least 90 days prior to dosing, including volunteers who are sterile due to vasectomy, bilateral orchiectomy, other surgical procedure, or known sterilizing medical condition. Male volunteers should use a barrier method such as a condom with any female partner of child-bearing potential and with any pregnant partner for 90 days after dosing.
1. History of type 1 diabetes or type 2 diabetes requiring systemic treatment
2. More than 1 of the following risk factors
2.1. BMI >32.0 kg/m²
2.2. Fasting blood glucose=125 mg/dl (7.0 mmol/l)
2.3. Glycosylated hemoglobin (HbA1C) =6.5%
3. Have a PR interval >210 ms, QRS complex >120 ms, or QTc interval >450 ms for males, >470 ms for females
4. History or presence of an abnormal ECG that, in the Investigator’s opinion, is clinically significant
5. 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)
6. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
7. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs with the exception of appendectomy and hernia repair surgery
8. History of inflammatory bowel disease (such as Crohn’s disease or ulcerative colitis), or active bowel inflammation (such as diverticulitis, with the exception of inactive diverticulosis)
9. History of ocular or intraocular conditions (such as cataract or diabetic retinopathy), active vitritis, history of or active uveitis, or active infections in the eye
10. History of alcoholism or drug addiction within 1 year prior to day -1
11. History of active or latent TB, regardless of treatment history
12. Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives of the investigational agent or 30 days before screening whichever is longer
13. Receipt of the first or second dose of a Coronavirus Disease 2019 (COVID-19) vaccine given Emergency Use Approvals (US) or approved COVID-19 vaccine in the past 7 days prior to dosing or planned to receive any COVID-19 vaccines during the trial
14. History of active viral, bacterial, or fungal infection requiring IV treatment with antibiotics within 14 days prior to day -1
15. Use of any immunosuppressive therapies within 8 weeks prior to the Screening evaluation
16. Use of any prescription medications/products within 14 days prior to day -1, unless deemed acceptable by the Investigator
17. Use of any over-the-counter, non-prescription preparations (including vitamins; minerals; and phytotherapeutic-, herbal-, and plant-derived preparations) within 7 days prior to day -1, unless deemed acceptable by the Investigator
18. Use of any drugs known to be strong inhibitors or inducers of cytochrome P450 (CYP)3A, from within 30 days prior to day -1 until Study Completion
19. Use of tobacco- or nicotine-containing products (including, but not limited to, cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) from within 6 months prior to day -1 until Study Completion
20. Use of alcohol-, grapefruit-, or caffeine-containing foods or beverages from within 72 h prior to day -1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 1. Maximum concentration (Cmax) of inavolisib measured using the plasma concentrations of inavolisib and total radioactivity concentrations in plasma and whole blood from blood samples collected at 0 and 336 h<br> 2. Area under the curve (AUC) of inavolisib measured using the plasma concentrations of inavolisib and total radioactivity concentrations in plasma and whole blood from blood samples collected at 0 and 336 h<br> 3. Bioavailability of inavolisib measured using the plasma concentrations of inavolisib and total radioactivity concentrations in plasma and whole blood from blood samples collected at 0 and 336 h<br>
- Secondary Outcome Measures
Name Time Method Percentage of the total radioactive dose excreted over the sampling interval and cumulatively across sampling intervals measured from urine and in fecal samples collected between 0 and 336 h