A study to investigate the absorption, metabolism, excretion, and bioavailability of oral and intravenous inavolisib in healthy volunteers
| ISRCTN | ISRCTN60043317 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60043317 |
| Secondary identifying numbers | Sponsor reference GP42652 |
- Submission date
- 02/04/2021
- Registration date
- 04/05/2021
- Last edited
- 29/04/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
Background and study aims
Breast cancer is the most commonly diagnosed cancer in women, with an estimated global incidence of 2,088,849 new cases and 626,679 deaths reported in 2018. Current treatments for advanced or metastatic disease focus on prolonging life and improving or maintaining quality of life. Preventing resistance to therapy and ultimately achieving a cure remain unmet needs in this disease setting.
Standard-of-care treatment options for patients with de novo metastatic disease, or for whom disease recurs following surgery and adjuvant treatment, include endocrine therapy, endocrine and targeted therapy combinations, or chemotherapy. For most patients, endocrine therapy alone or in combination with a targeted therapy is the treatment of choice in the metastatic setting.
Inavolisib as a single agent, or inavolisib in combination with other anti-cancer therapies, is being developed by Roche, for the treatment of locally advanced tumors or solid tumors with the PIK3CA-mutatation that have spread to other sites, including breast cancer. The development of inavolisib as a single agent and in various other combinations for other indications beyond breast cancer is ongoing.
This study will investigate the absorption, metabolism, excretion, and bioavailability of inavolisib in healthy volunteers. Information on the amount of active inavolisib available to the body using the current method of taking the drug will be helpful to plan future studies and may be useful to interpret data from these studies on how inavolisib moves through and interacts with the body. The results from this study may guide future study designs using special populations or evaluating the potential for drug-drug interactions.
Who can participate?
Up to 8 healthy male and female volunteers aged 18 to 65 years. Male volunteers are limited to 3 volunteers or less.
What does the study involve?
Participants will receive a single dose (9 mg) of inavolisib as a capsule taken by mouth in a fasted state. After 2 h 58 min, participants will receive a single intravenous infusion (100 μg) of inavolisib. Participants will be followed up for collection of blood, urine, and fecal samples over the following 336 h period.
What are the possible benefits and risks of participating?
High blood sugar, inflammation or ulcers of the mouth, rash, and diarrhea have been identified as risks for people receiving inavolisib treatment. These risks may require either stopping or reducing the dose of inavolisib and may have the potential to cause life-threatening conditions. Therefore, close monitoring and a robust risk-mitigation strategy will be used during this study. Results in previous studies have shown the inavolisib is well tolerated and there are no additional safety concerns beyond those associated with expected toxicities and effects of this class of drugs.
Where is the study run from?
Genentech, Inc. (USA)
When is the study starting and how long is it expected to run for?
From November 2020 to April 2021
Who is funding the study?
Genentech, Inc. (USA)
Who is the main contact?
global-roche-genentech-trials@gene.com
Contact information
Scientific
1 DNA Way
South San Francisco
94080
United States of America
| Phone | +1 888-662-6728 |
|---|---|
| global-roche-genentech-trials@gene.com |
Study information
| Study design | Phase 1 single-center open-label non-randomized study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | A phase 1, open-label, single-center study to investigate the absorption, metabolism, excretion, and absolute bioavailability of a single oral dose of [14C]-labeled inavolisib and an iv tracer dose of [13C6]-labeled inavolisib in a single cohort of healthy volunteers |
| Study hypothesis | To investigate the absorption, metabolism, excretion, and absolute bioavailability of Inavolisib in healthy volunteers |
| Ethics approval(s) | Approved 09/02/2021, Salus IRB (2111 W. Braker Lane, Suite 100, Austin, Texas 78758, USA; +1 512-380-1244; salus@salusirb.com), ref: GP42652 |
| Condition | The absorption, metabolism, excretion, and bioavailability of a PI3K inhibitor drug in healthy volunteers |
| Intervention | The participants will each receive a single 9 mg (approximately 200 μCi) oral capsule dose of [14C]-inavolisib administered in a fasted state and followed after 2 h 58 min by a single 100 μg intravenous (IV) dose of [13C6]-inavolisib administered as an IV push over 2 min. Participants will be followed up for regular collection of blood, urine, and fecal samples over a 336 h period. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | inavolisib |
| Primary outcome measure | 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 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 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 |
| Secondary outcome measures | 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 |
| Overall study start date | 03/11/2020 |
| Overall study end date | 23/04/2021 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 6 |
| Total final enrolment | 8 |
| Participant inclusion criteria | 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. |
| Participant exclusion criteria | 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 until Study Completion, unless deemed acceptable by the Investigator 21. Participation in strenuous exercise (a new exercise program or participation in any unusually strenuous physical exertion) from 48 h prior to day -1 and during the period of confinement at the study site 22. Poor peripheral venous access 23. History of malignancy, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ of breast, or Stage I uterine cancer 24. Donation of blood from 30 days prior to Screening through Study Completion, Clinic Discharge, or Early Termination, inclusive, or of plasma from 2 weeks prior to Screening through Study Completion, Clinic Discharge, or Early Termination, inclusive 25. Receipt of blood products within 2 months prior to day -1 26. Any clinically significant deviations from normal ranges in coagulation factors 27. Any acute or chronic condition that, in the opinion of the Investigator, would limit the volunteer’s ability to complete and/or participate in this clinical study 28. Exposure to significant diagnostic or therapeutic radiation (e.g., serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to day -1 29. Participation in more than three radiolabeled drug studies in the last 12 months 30. Volunteers who, in the opinion of the Investigator (or designee), should not participate in this study 31. Female volunteers: pregnant, lactating, breastfeeding, or of childbearing potential |
| Recruitment start date | 12/03/2021 |
| Recruitment end date | 09/04/2021 |
Locations
Countries of recruitment
- United States of America
Study participating centre
Madison
53704
United States of America
Sponsor information
Industry
1 DNA Way
South San Francisco
94080
United States of America
| Phone | +1 888-662-6728 |
|---|---|
| global-roche-genentech-trials@gene.com | |
| Website | www.roche.com/about_roche/roche_worldwide.htm |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Genentech, Inc., Genentech USA, Inc., Genentech USA
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/01/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to this being a voluntary posting. |
Editorial Notes
12/04/2021: Trial’s existence confirmed by Salus IRB.
