Modular Clinical Pharmacology Study to Evaluate the Drug-drug Interaction Potential and Relative Bioavailability of Saruparib
A Modular Phase I, Open-label Study to Assess the Safety, Pharmacokinetics, and Drug Interaction Potential and Relative Bioavailability of Saruparib in Patients With Advanced Solid Malignancies
2 other identifiers
interventional
41
3 countries
4
Brief Summary
A Phase I modular study to assess the effect of oral saruparib on other treatments in patients with advanced solid malignancies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2025
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 21, 2025
CompletedStudy Start
First participant enrolled
March 25, 2025
CompletedFirst Posted
Study publicly available on registry
March 27, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 3, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2026
CompletedMarch 27, 2026
February 1, 2026
11 months
March 21, 2025
March 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
Module 1: Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf) of digoxin, furosemide, metformin and rosuvastatin when dosed alone and in combination with saruparib
To evaluate the effects of saruparib on the PK of substrates of human drug transporters digoxin, furosemide, metformin hydrochloride, and rosuvastatin in participants with advanced solid malignancies.
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 1: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of digoxin, furosemide, metformin and rosuvastatin when dosed alone and in combination with saruparib
To evaluate the effects of saruparib on the PK of substrates of human drug transporters digoxin, furosemide, metformin hydrochloride, and rosuvastatin in participants with advanced solid malignancies.
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 1: Maximum observed plasma (peak) drug concentration (Cmax) of digoxin, furosemide, metformin and rosuvastatin when dosed alone and in combination with saruparib
To evaluate the effects of saruparib on the PK of substrates of human drug transporters digoxin, furosemide, metformin hydrochloride, and rosuvastatin in participants with advanced solid malignancies.
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 2: AUClast between DC and RC tablets of saruparib
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: AUCinf between DC and RC tablets of saruparib
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: Cmax between DC and RC tablets of saruparib
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: AUClast of DC saruparib tablets in the presence and absence of rabeprazole relative to the RC tablet
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
Period 3: Days 4 to 6
Module 2: AUCinf of DC saruparib tablets in the presence and absence of rabeprazole relative to the RC tablet
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
Period 3: Days 4 to 6
Module 2: Cmax of DC saruparib tablets in the presence and absence of rabeprazole relative to the RC tablet
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
Period 3: Days 4 to 6
Secondary Outcomes (26)
Module 1: Time to reach peak or maximum observed concentration following drug administration (tmax) of digoxin, furosemide, metformin and rosuvastatin when administered alone and in combination with saruparib, in plasma
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 1: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz) of digoxin, furosemide, metformin and rosuvastatin when administered alone and in combination with saruparib, in plasma
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of digoxin, furosemide, metformin and rosuvastatin when administered alone and in combination with saruparib, in plasma
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 1: Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) of digoxin, furosemide, metformin and rosuvastatin when administered alone and in combination with saruparib, in plasma
Period 1: Days 1 to 5. Period 2: Days 5 to 9
Module 1: Area under concentration time curve in the dosing interval (AUCtau) of saruparib after multiple doses in plasma
Period 2: Days 5 to 9
- +21 more secondary outcomes
Study Arms (3)
Treatment Cohort (Module 1)
ACTIVE COMPARATORPeriod 1: participants will receive a single oral dose of cocktail substrate (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single dose saruparib from Day 1 to 9, and a single dose of cocktail substrate on Day 5 in combination with saruparib. Period 3: participants will receive a single oral dose of saruparib daily.
Saruparib RC Cohort (Module 2)
ACTIVE COMPARATORPeriod 1: participants will receive a single dose of RC saruparib. Period 2: participants will receive a single dose of DC saruparib. Period 3: participants will receive rabeprazole twice daily from Day 1 to 3, and a single dose of rabeprazole prior to DC saruparib on Day 4. Period 4: participants will receive RC saruparib daily for up to 3 cycles.
Saruparib DC Cohort (Module 2)
ACTIVE COMPARATORPeriod 1: participants will receive a single dose of DC saruparib. Period 2: participants will receive a single dose of RC saruparib. Period 3: participants will receive rabeprazole twice daily from Day 1 to 3, and a single dose of rabeprazole prior to DC saruparib on Day 4. Period 4: participants will receive RC saruparib daily for up to 3 cycles.
Interventions
Module 1: Period 2: participants will receive saruparib orally once daily from Day 1 to Day 9. On Day 5 saruparib will be administered orally in combination with the cocktail of substrates. Period 3: participants will receive saruparib orally once daily for up to 3 cycles of 28 days each. Module 2: Period 1 and Period 2: participants will receive a single oral dose of DC or RC saruparib. Period 3: participants will receive an oral dose of rabeprazole twice daily from Day 1 to 3, and a single oral dose of rabeprazole prior to DC saruparib on Day 4. Period 4: participants will receive an oral dose of RC saruparib daily for 3 cycles.
Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5.
Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5.
Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5.
Period 3: Participants will receive two doses of rabeprazole per day from Day 1 to 3. On Day 4, participants will receive a dose of rabeprazole followed by DC saruparib.
Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5.
Eligibility Criteria
You may qualify if:
- Participants with documented evidence of locally advanced unresectable or metastatic solid tumours, excluding lymphoma, who have exhausted standard of care options (or for which no standard therapies exist) and may be suitable for saruparib monotherapy treatment in the opinion of the investigator.
- Adequate organ and marrow function (in the absence of transfusions or growth factor support within 28 days prior to enrolment).
- An ECOG PS: 0 to 1 with no deterioration within 1 week prior to the screening visit.
- Life expectancy ≥ 12 weeks.
You may not qualify if:
- Evidence of active and uncontrolled hepatitis B and/or hepatitis C. Screening for hepatitis B and hepatitis C is not required, criteria is based on medical history.
- Participants with controlled HIV need to meet the following criteria (screening for HIV is not required, criteria are based on medical history):
- Undetectable viral RNA load less than 400 copies/mL in the last 4 weeks prior to first dose of study intervention.
- CD4+ count of ≥ 350 cells/μL.
- No history of acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months, and stable on the same anti-HIV medications for at least 6 months. Screening for HIV is not required.
- Any other evidence of diseases, such as severe or uncontrolled systemic diseases or active uncontrolled infections, including but not limited to uncontrolled major seizure disorder, active bleeding diseases, superior vena cava syndrome, or history of allogenic organ transplant
- Active tuberculosis infection
- Any of the following cardiac criteria:
- Mean resting QTcF \> 470 ms obtained from triplicate ECGs performed at screening and averaged. At each timepoint at which triplicate ECG are required, 3 individual ECG tracings should be obtained in succession, no more than 2 minutes apart. The full set of triplicates should be completed within 5 minutes.
- Any factors that increase the risk of QT prolongation, shortening or risk of arrhythmic events such as hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in an immediate family member.
- History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted if deemed medically safe by the investigator.
- Other cardiovascular diseases with the exception of alopecia, and peripheral neuropathy; any unresolved toxicities from prior anticancer therapy greater than CTCAE Grade 1 at the time of study enrolment.
- Any known history of persisting (\> 2 weeks) severe pancytopenia due to any cause (absolute neutrophil count \< 0.5 × 109/L or platelets \< 50 × 109/L).
- Spinal cord compression, or brain metastases for at least 4 weeks prior to start of study intervention unless asymptomatic and stable (ie, not requiring a dose of steroids ≥ 10 mg for more than 2 weeks). A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and signing the main study ICF.
- Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent \[within 6 months\] haemorrhagic stroke, proliferative diabetic retinopathy).
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Parexelcollaborator
Study Sites (4)
Research Site
Sofia, 1618, Bulgaria
Research Site
Chisinau, MD-2025, Moldova
Research Site
Bucharest, 022338, Romania
Research Site
Cluj-Napoca, 400015, Romania
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 21, 2025
First Posted
March 27, 2025
Study Start
March 25, 2025
Primary Completion
February 3, 2026
Study Completion
April 30, 2026
Last Updated
March 27, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.