Advanced Solid MalignanciesPhase 1NCT06899061
Modular Clinical Pharmacology Study to Evaluate the Drug-drug Interaction Potential and Relative Bioavailability of Saruparib
A Phase 1 study testing Saruparib, Digoxin and Furosemide in people with Advanced Solid Malignancies, run by AstraZeneca at 4 sites in 3 countries.
Trial summary
A Phase I modular study to assess the effect of oral saruparib on other treatments in patients with advanced solid malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Malignancies
- What is being tested?
- Saruparib, Digoxin and Furosemide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 25 Mar 2025to 19 May 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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).
- Participants with history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). If there is no clinical MDS/AML suspicion, no specific screening for MDS/AML is required.
- Refractory nausea and vomiting, chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study intervention.
- Known allergy or hypersensitivity to study intervention or any of the excipients of the study intervention.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the study intervention or interpretation of participant safety or study results.
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
- Uncontrolled intercurrent illness within the last 12 months, including but not limited to, serious chronic GI conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent.
- Module 1:
- Current or planned use of calcium channel blockers up to the end of Period 2.
- Current and/or regular use of any of the study interventions in the cocktail substrates that cannot be substituted.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Romania2 sites
Research Site
Bucharest, 022338
Research Site
Cluj-Napoca, 400015
About this study
Official title: 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
A Phase I modular study to assess the effect of oral saruparib on other treatments in patients with advanced solid malignancies.
Read the detailed description
Module 1 of the study is a Phase I, open-label study to assess the effects of saruparib on the PK of substrates digoxin (P-gp), furosemide (OAT1/3), metformin hydrochloride (OCT2/MATE1/2K), and rosuvastatin (OATP1B1/3) in participants with advanced solid malignancies.
Module 2 of the study is a Phase I, open-label, 4-treatment period, multi-centre, relative bioavailability, PPI effect, randomised, crossover study of saruparib tablets manufactured using a direct compression (DC) process in participants with advanced solid malignancies.
Module 1 of the study will include:
- A Screening period of 28 days prior to Day 1.
- Period 1: a single dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1.
- A washout period of 1 to 3 days between Period 1 and Period 2.
- Period 2: continuous dosing of saruparib from Day 1 to Day 9. On Day 5 saruparib will be administered in combination with the cocktail of substrates.
- Period 3: a dose of saruparib per day for up to 3 cycles of 28 days each.
- An End of Study visit up to 3 days after the last dose in Period 3.
Module 2 of the study will include:
- A Screening period of 28 days prior to Day 1.
- Period 1 and Period 2: a single dose of roller compaction (RC) or DC saruparib.
- Period 3: from Day 1 to 3, two doses of rabeprazole per day. On Day 4, a dose of rabeprazole followed by DC saruparib.
- A washout period of at least 3 days between Period 1 and Period 3, and between Period 2 and Period 3.
- Period 4: a single dose of RC saruparib for up to 3 cycles.
- An End of Study visit up to 3 days after the last dose in Period 4.
- Conditions
- Advanced Solid Malignancies
- Being tested
- Saruparib, Digoxin, Furosemide, Metformin Hydrochloride, Rosuvastatin
- Keywords
- Single-stranded DNA, Poly(ADP-ribose) polymerase 1, Transporter substrates, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaruparibDrug
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.
DigoxinDrug
Also called P-gp
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.
FurosemideDrug
Also called OCT2
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.
Metformin HydrochlorideDrug
Also called OAT1/3, MATE1/2K
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.
RosuvastatinDrug
Also called OATP1B1/3
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.
RabeprazoleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Cohort (Module 1) | Active comparator | Period 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. Receives: Drug: Saruparib; Drug: Digoxin; Drug: Furosemide; Drug: Metformin Hydrochloride; Drug: Rosuvastatin |
| Saruparib RC Cohort (Module 2) | Active comparator | Period 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. Receives: Drug: Saruparib; Drug: Rabeprazole |
| Saruparib DC Cohort (Module 2) | Active comparator | Period 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. Receives: Drug: Saruparib; Drug: Rabeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: 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
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: 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
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: 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
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: 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
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: AUClast of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: Minimum blood plasma concentration reached during a dosing interval (Cmin) of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: From Screening (Day -28) to Follow up, up to 129 days
Module 1: Cmax of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: CL/F of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: Vz/F of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: t1/2λz of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 1: tmax of saruparib after multiple doses in plasma
To assess PK, safety and tolerability of saruparib following oral dosing.
Measured: Period 2: Days 5 to 9
Module 2: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
To assess the safety and tolerability of saruparib.
Measured: From Screening (Day -28) to Follow up, up to 167 days
Module 2: Cmax of saruparib via DC and RC tablets
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: tmax of saruparib via DC and RC tablets
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: t½λz of saruparib via DC and RC tablets
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: λz of saruparib via DC and RC tablets
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: CL/F of saruparib via DC and RC tablets
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: Vz/F of saruparib via DC and RC tablets
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: Cmax of saruparib via DC tablets in the presence of rabeprazole
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 3: Days 4 to 6
Module 2: tmax of saruparib via DC tablets in the presence of rabeprazole
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 3: Days 4 to 6
Module 2: t½λz of saruparib via DC tablets in the presence of rabeprazole
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 3: Days 4 to 6
Module 2: λz of saruparib via DC tablets in the presence of rabeprazole
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 3: Days 4 to 6
Module 2: CL/F of saruparib via DC tablets in the presence of rabeprazole
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 3: Days 4 to 6
Module 2: Vz/F of saruparib via DC tablets in the presence of rabeprazole
To compare the PK of saruparib manufactured using a DC process versus RC process in participants with advanced solid malignancies.
Measured: Period 3: Days 4 to 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2025
- Study start25 Mar 2025
- Primary completion3 Feb 2026
- Study completion19 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid MalignanciesStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Module 1: Single Group Module 2: Crossover
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06899061
- Sponsor's protocol ID
- D9723C00002
- Other IDs
- 2024-513692-41-00
- Status last verified
- Sep 2026
- First submitted
- 21 Mar 2025
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06899061
- Acronym / sponsor ID
- D9723C00002
- Conditions
- Advanced Solid Malignancies
- Keywords
- Single-stranded DNA, Poly(ADP-ribose) polymerase 1, Transporter substrates, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 41 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 25 Mar 2025 (actual)
- Primary completion
- 3 Feb 2026 (actual)
- Study completion
- 19 May 2028 (estimated)
- First posted
- 27 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase I modular study to assess the effect of oral saruparib on other treatments in patients with advanced solid malignancies.
Detailed description
Module 1 of the study is a Phase I, open-label study to assess the effects of saruparib on the PK of substrates digoxin (P-gp), furosemide (OAT1/3), metformin hydrochloride (OCT2/MATE1/2K), and rosuvastatin (OATP1B1/3) in participants with advanced solid malignancies.
Module 2 of the study is a Phase I, open-label, 4-treatment period, multi-centre, relative bioavailability, PPI effect, randomised, crossover study of saruparib tablets manufactured using a direct compression (DC) process in participants with advanced solid malignancies.
Module 1 of the study will include:
- A Screening period of 28 days prior to Day 1.
- Period 1: a single dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1.
- A washout period of 1 to 3 days between Period 1 and Period 2.
- Period 2: continuous dosing of saruparib from Day 1 to Day 9. On Day 5 saruparib will be administered in combination with the cocktail of substrates.
- Period 3: a dose of saruparib per day for up to 3 cycles of 28 days each.
- An End of Study visit up to 3 days after the last dose in Period 3.
Module 2 of the study will include:
- A Screening period of 28 days prior to Day 1.
- Period 1 and Period 2: a single dose of roller compaction (RC) or DC saruparib.
- Period 3: from Day 1 to 3, two doses of rabeprazole per day. On Day 4, a dose of rabeprazole followed by DC saruparib.
- A washout period of at least 3 days between Period 1 and Period 3, and between Period 2 and Period 3.
- Period 4: a single dose of RC saruparib for up to 3 cycles.
- An End of Study visit up to 3 days after the last dose in Period 4.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Module 1: Single Group Module 2: Crossover
| Arm | Type | Receives |
|---|---|---|
| Treatment Cohort (Module 1) | Active comparator | Drug: Saruparib, Drug: Digoxin, Drug: Furosemide, Drug: Metformin Hydrochloride, Drug: RosuvastatinPeriod 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 comparator | Drug: Saruparib, Drug: RabeprazolePeriod 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 comparator | Drug: Saruparib, Drug: RabeprazolePeriod 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (24 listed)
- 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):
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SaruparibModule 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. | Drug | Saruparib DC Cohort (Module 2), Saruparib RC Cohort (Module 2), Treatment Cohort (Module 1) |
| DigoxinAlso: P-gpPeriod 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. | Drug | Treatment Cohort (Module 1) |
| FurosemideAlso: OCT2Period 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. | Drug | Treatment Cohort (Module 1) |
| Metformin HydrochlorideAlso: OAT1/3, MATE1/2KPeriod 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. | Drug | Treatment Cohort (Module 1) |
| RosuvastatinAlso: OATP1B1/3Period 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. | Drug | Treatment Cohort (Module 1) |
| RabeprazolePeriod 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. | Drug | Saruparib DC Cohort (Module 2), Saruparib RC Cohort (Module 2) |
Primary outcome
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
Time frame: Period 1: Days 1 to 5. Period 2: Days 5 to 9
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.
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
Time frame: Period 1: Days 1 to 5. Period 2: Days 5 to 9
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.
Module 1: Maximum observed plasma (peak) drug concentration (Cmax) of digoxin, furosemide, metformin and rosuvastatin when dosed alone and in combination with saruparib
Time frame: Period 1: Days 1 to 5. Period 2: Days 5 to 9
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.
Module 2: AUClast between DC and RC tablets of saruparib
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
Module 2: AUCinf between DC and RC tablets of saruparib
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
Module 2: Cmax between DC and RC tablets of saruparib
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
Module 2: AUClast of DC saruparib tablets in the presence and absence of rabeprazole relative to the RC tablet
Time frame: Period 3: Days 4 to 6
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
Module 2: AUCinf of DC saruparib tablets in the presence and absence of rabeprazole relative to the RC tablet
Time frame: Period 3: Days 4 to 6
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
Module 2: Cmax of DC saruparib tablets in the presence and absence of rabeprazole relative to the RC tablet
Time frame: Period 3: Days 4 to 6
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
26 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Period 2: Days 5 to 9
Module 1: AUClast of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 1: Minimum blood plasma concentration reached during a dosing interval (Cmin) of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 1: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Screening (Day -28) to Follow up, up to 129 days
Module 1: Cmax of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 1: CL/F of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 1: Vz/F of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 1: t1/2λz of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 1: tmax of saruparib after multiple doses in plasma
Time frame: Period 2: Days 5 to 9
Module 2: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Screening (Day -28) to Follow up, up to 167 days
Module 2: Cmax of saruparib via DC and RC tablets
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: tmax of saruparib via DC and RC tablets
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: t½λz of saruparib via DC and RC tablets
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: λz of saruparib via DC and RC tablets
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: CL/F of saruparib via DC and RC tablets
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: Vz/F of saruparib via DC and RC tablets
Time frame: Period 1: Days 1 to 3. Period 2: Days 1 to 3
Module 2: Cmax of saruparib via DC tablets in the presence of rabeprazole
Time frame: Period 3: Days 4 to 6
Module 2: tmax of saruparib via DC tablets in the presence of rabeprazole
Time frame: Period 3: Days 4 to 6
Module 2: t½λz of saruparib via DC tablets in the presence of rabeprazole
Time frame: Period 3: Days 4 to 6
Module 2: λz of saruparib via DC tablets in the presence of rabeprazole
Time frame: Period 3: Days 4 to 6
Module 2: CL/F of saruparib via DC tablets in the presence of rabeprazole
Time frame: Period 3: Days 4 to 6
Module 2: Vz/F of saruparib via DC tablets in the presence of rabeprazole
Time frame: Period 3: Days 4 to 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Saruparib, Digoxin and Furosemide in people with Advanced Solid Malignancies, run by AstraZeneca at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Romania, Bulgaria, Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Period 1: Days 1 to 5. Period 2: Days 5 to 9). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.