Effect of a single dose of cyclosporine on the single-dose pharmacokinetics of pralsetinib in healthy subjects Not Applicable
Conditions
Interventions
All participants will receive the following treatments:
Day 1: 200 mg pralsetinib (2 x 100-mg capsules) administered orally after an overnight fast of at least 10 hours.
Sponsors
Roche (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Within BMI range 18.5 to 30.0 kg/m², inclusive 2. In good health, determined by no clinically significant findings from medical history, physical examination, laboratory profiles, 12-lead ECG, and vital signs 3. Clinical laboratory evaluations (including chemistry panel [fasted at least 10 hours], complete blood count [CBC], and urinalysis [UA] with complete microscopic analysis within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator; 4. Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (Day -1) (does include alcohol; Appendix A) and agrees to abstain from recreational drug use throughout the study, from screening until follow-up 5. 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 45 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 6. Males will either be sterile or agree to use contraception 7. Receive an explanation of the mandatory {WGS} [and/or] {WES} component of the study
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 06/06/2023: 1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator) 2. History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study 3. History of significant hypersensitivity, idiosyncratic reaction, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator 4. Use of oral antibiotics to treat an active infection within 4 weeks or intravenous antibiotics to treat an active infection within 8 weeks prior to Screening 5. History of stomach or intestinal surgery or resection prior to first dosing that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed 6. History or presence of an abnormal ECG, which, in the Investigator’s opinion, is clinically significant 7. History of alcoholism or drug addiction within 2 years prior to Check-in (Day -1) 8. History of active or latent TB, regardless of treatment history, or has a positive screening test for latent mycobacterium infection by QuantiFERON® TB Gold (Appendix A). Indeterminate results may be confirmed by repeat or by a purified protein derivative (PPD) skin test 9. Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, or administered treatment with another investigational drug within 5 times the elimination half-life, if known (if marketed product) or within 30 days (if the elimination half-life is unknown) prior to first dose of pralsetinib (Day 1). The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study 10. Receipt of any vaccines (including coronavirus disease-2019 [COVID-19], seasonal flu, and H1N1 vaccines) within 14 days prior to Screening, unless deemed acceptable by the Investigator and Sponsor 11. Prior exposure to pralsetinib or other RET inhibitors 12. Has a positive pregnancy test or is lactating (females only) 13. Has a positive urine drug or breath or urine alcohol result at Screening or Check-in 14. Has a positive urine cotinine result at Screening or Check-in 15. Use of any prescription medications/products within 14 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator 16. Use of any over-the-counter, nonprescription preparations (including vitamins; minerals; and phytotherapeutic-, herbal-, and plant-derived preparations) within 7 days prior to Check-in (Day 1), unless deemed acceptable by the Investigator. After first dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the Investigator or designee to treat AEs. Hormone replacement therapy will not be allowed 17. Use of any drugs known to be a strong inhibitor and/or inducer of CYP1A2, CYP2D6, CYP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 06/06/2023: 1. Maximum plasma concentration (Cmax), time to maximum observed concentration (t max), area under the concentration-time curve from Hour 0 to the last measurable concentration (AUC 0-t), AUC from Hour 0 to “192,” where “192” is a common nominal timepoint across participants (AUC 0-“192”), AUC from time zero to infinity (AUC 0-8) and apparent terminal elimination half-life (t 1/2) of pralsetinib when administered alone and in combination with cyclosporine, measured using noncompartmental methods of analysis at pre-dose and 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 144 h, 192 h, 216 h, 240 h (cyclosporine arm only) and 264 h (cyclosporine arm only) post dose Previous primary outcome measures: 1. t max, time to maximum observed concentration following SC administration measured from plasma samples taken QD with the exception of Days 6, 8, 15, 17, and 19, up to 3 weeks 2. AUC 0-t , area under the concentration-time curve from Hour 0 to the last measurable concentration, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations, measured from plasma samples taken QD with the exception of Days 6, 8, 15, 17, and 19, up to 3 weeks 3. AUC from Hour 0 to “t,” where “t” is a common nominal timepoint across subjects (AUC 0-“t”), measured from plasma samples taken QD with the exception of Days 6, 8, 15, 17, and 19, up to 3 weeks 4. AUC from time zero to infinity (AUC 0-), measured from plasma samples taken QD with the exception of Days 6, 8, 15, 17, and 19, up to 3 weeks 5. AUC from time zero to the last quantifiable concentration (AUC last), measured from plasma samples taken QD with the exception of Days 6, 8, 15, 17, and 19, up to 3 weeks 6. Percentage of AUC that is due to | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 06/06/2023: 1. Number of participants with treatment-emergent adverse events (TEAEs) and severity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0), from study initiation up to follow-up at Day 38 2. Number of participants with abnormal electrocardiogram (ECG) parameters measured using triplicate 12-lead ECG at screening, check-in (Day -1) Day 1, 2, 5, 9, 10, 11, 14, 18, and at discharge (Day 21) Previous secondary outcome measures: 1. AEs (incidence, nature, and severity), according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), recorded throughout the study 2. Incidence of electrocardiogram (ECG) abnormalities, as measured by triplicate 12-lead ECG at screening, Day 1, 2, 6, 9, 10, 11, 14, 18, and 21 | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed