A study to evaluate the drug-drug interaction potential of pralsetinib in combination with substrates of various transporters or CYP enzymes or a combined oral contraceptive in participants with advanced or metastatic solid tumors that are not responsive to standard therapies

A Phase I, two-arm, open-label study to evaluate the clinical drug-drug interaction potential of pralsetinib in combination with sensitive transporter substrates, sensitive CYP substrates, or a combined oral contraceptive in patients with advanced or metastatic solid tumors that are not responsive to standard therapies or for which there is no effective therapy

Status

Recruiting

Phases

Phase 1

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN14442671

Enrollment

Registered

2023-01-05

Start date

2023-04-11

Completion date

Unknown

Last updated

2024-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid tumors Cancer

Interventions

Current interventions as of 30/09/2024: Participants will be allocated to either treatment arm depending on local circumstances and requirements, based on investigator and sponsor decisions. Arm A: P

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Participants who are 18 years or more at the time of informed consent 2. Eastern Cooperative Oncology Group (ECOG) performance =2 3. Participants with histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumours that are not responsive to standard therapies or for which there is no effective therapy

Exclusion criteria

Exclusion criteria: 1. Clinically relevant abnormal medical history, abnormal findings on physical examination, vital signs, ECG, or laboratory tests at screening that the investigator judges as likely to interfere with the objectives of the trial or the safety of the participant 2. Surgery (e.g., stomach bypass) or medical condition that might significantly affect the absorption of medicines (as judged by the investigator) 3. History of pneumonitis within the last 12 months 4. History of active or latent tuberculosis, regardless of treatment history, or has a positive screening test for latent mycobacterium tuberculosis infection 5. Serious infection requiring intravenous or systemic antibiotics within 7 days prior to initiation of study treatment 6. Cardiovascular issues 7. Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease 8. Radiotherapy or radiosurgery to any site within 14 days before check-in or more than 30 Gy of radiotherapy to the lung in the 6 months before check-in 9. Medical conditions or underlying diseases that constitute contraindications on the use of the substrates or probes used in this study including hypersensitivity to the drugs administered during the study 10. Participation in another investigational drug trial within 30 days prior to study drug administration or exposure to more than 3 new investigational agents within 12 months prior to study drug administration 11. Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody at screening. A negative polymerase chain reaction (PCR) test overrides a positive serological test. 12. Human immunodeficiency virus (HIV) antibodies 1/2 at screening (added 30/09/2024: Individuals with a positive HIV test at screening are eligible, provided they are stable on antiretroviral therapy, have a CD4 count =200/µL, and have an undetectable viral load).

Design outcomes

Primary

Measure	Time frame
1. Maximum observed concentration (Cmax) of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Days 1-3 and Days 10-12. Cmax of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20. 2. Area under the concentration-time curve from time 0 to time t (AUC0-t) where 0 is the time point of the last administration, where t is the last point with concentrations above the lower limit of quantification (LLOQ) of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Days 1-3 and Days 10-12. AUC0-t of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20. 3. Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Days 1-3 and Days 10-12, AUC0-inf of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20. All PK par	—

Measure

Time frame

1. Maximum observed concentration (Cmax) of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Days 1-3 and Days 10-12. Cmax of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20. 2. Area under the concentration-time curve from time 0 to time t (AUC0-t) where 0 is the time point of the last administration, where t is the last point with concentrations above the lower limit of quantification (LLOQ) of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Days 1-3 and Days 10-12. AUC0-t of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20. 3. Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Days 1-3 and Days 10-12, AUC0-inf of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20. All PK par

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Secondary

Measure	Time frame
Current secondary outcome measures as of 30/09/2024: 1. Cmax at steady state of pralsetinib measured from blood samples at multiple timepoints from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 2. Minimum observed concentration (Cmin) at steady state of pralsetinib measured from blood samples at multiple timepoints from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 3. Time to attain maximum observed concentration (Tmax) of pralsetinib measured from blood samples at multiple timepoints from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B). Tmax of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Day 1-3 and Days 10-12, Tmax of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively, from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20 4. Area under the concentration-time curve up to time t (AUC0-t) where 0 is the time point of the last administration, where t is the last point with concentrations above the LLOQ of pralsetinib measured from blood samples at multiple time-points from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 5. Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of pralsetinib measured from blood samples at multiple time-points Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 6. Percentage of estimated part for the calculation of AUC0-inf ((AUC0-inf-AUC0-t)/AUC0-inf)*100% (%AUCextra) of pralsetinib measured from blood samples at multiple time-points from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B). %AUCextra of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pr	—

Measure

Time frame

Current secondary outcome measures as of 30/09/2024: 1. Cmax at steady state of pralsetinib measured from blood samples at multiple timepoints from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 2. Minimum observed concentration (Cmin) at steady state of pralsetinib measured from blood samples at multiple timepoints from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 3. Time to attain maximum observed concentration (Tmax) of pralsetinib measured from blood samples at multiple timepoints from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B). Tmax of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pralsetinib on Day 10 from blood samples collected at multiple timepoints from Day 1-3 and Days 10-12, Tmax of CYP substrates (midazolam, warfarin and montelukast) and COC (norethindrone, ethinyl estradiol) when given alone on Day 1 and Day 5, respectively, and when co-administered with pralsetinib on Day 14 and Day 18, respectively, from blood samples collected at multiple timepoints from Days 1-7 and Days 14-20 4. Area under the concentration-time curve up to time t (AUC0-t) where 0 is the time point of the last administration, where t is the last point with concentrations above the LLOQ of pralsetinib measured from blood samples at multiple time-points from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 5. Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of pralsetinib measured from blood samples at multiple time-points Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B) 6. Percentage of estimated part for the calculation of AUC0-inf ((AUC0-inf-AUC0-t)/AUC0-inf)*100% (%AUCextra) of pralsetinib measured from blood samples at multiple time-points from Day 10 to Day 12 (Arm A) and Day 14 to Day 20 (Arm B). %AUCextra of transporter substrates (digoxin, furosemide, metformin, rosuvastatin) when given alone on Day 1 and when co-administered with pr

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Countries

Bulgaria, Georgia, Moldova, Romania, Ukraine, United Kingdom

Contacts

Public ContactClinical Trials

global.trial_information@roche.com+41 616878333

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026