Solid TumoursPhase 1NCT01929603
Study to Assess the Effect of Rifampicin (CYP Inducer) on Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours
A Phase 1 study testing Pharmacokinetic sampling, Rifampicin and Olaparib tablet dosing in people with Solid Tumours, run by AstraZeneca at 5 sites in 2 countries.
Trial summary
This is a 2-part study in patients with advanced solid tumours. Part A will investigate the effect of rifampicin on the PK parameters of olaparib in patients; Part B will allow patients continued access to olaparib after the PK phase and will provide additional safety data. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Solid Tumours
- What is being tested?
- Pharmacokinetic sampling, Rifampicin and Olaparib tablet dosing
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Dec 2013to Nov 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For inclusion in the study, patients should fulfil the following criteria:
- Provision of written informed consent prior to any study-specific procedures.
- Patients aged greater than or equal to 18 years.
- Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
- 4 Patients must have normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below: Haemoglobin (Hb) greater than or equal to 10.0 g/dL, with no blood transfusions in the previous 28 days.
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L. White blood cells (WBC) greater than 3 x 109/L. Platelet count greater than or equal to 100 x 109/L. Total bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN) (except in the case of Gilbert's disease).
Show all 38Show fewer
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) less than or equal to 2.5 x institutional ULN unless liver metastases are present, in which case it must be less than or equal to 5x ULN, Serum creatinine less than or equal to 1.5 x institutional ULN.
- 5. Calculated serum creatinine clearance greater than 50 mL/min (using Cockroft-Gault formula or by 24 hour urine collection).
- 6. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- 7. Patients must have a life expectancy of greater than or equal to 16 weeks. 8. Evidence of non-childbearing status for women of childbearing potential, or post menopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1 of Part A. Post-menopausal is defined as: Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.
- Luteinising hormone and follicle stimulating hormone levels in the post menopausal range for women under 50 years of age.
- Radiation-induced oophorectomy with last menses greater than 1 year ago. Chemotherapy-induced menopause with greater than 1 year interval since last menses.
- Surgical sterilisation (bilateral oophorectomy or hysterectomy). 9. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- 10. Patients must be on a stable concomitant medication regimen (with the exception of electrolyte supplements), defined as no changes in medication or in dose within the 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab, and corticosteroids, which should be at a stable dose for at least 4 weeks prior to the start of olaparib dosing.
- Exclusion Criteria:- Patients should not enter the study if any of the following exclusion criteria are fulfilled.
- Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff, its agents, and/or staff at the study site).
- Previous enrolment in the present study.
- Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study, as long as these were started at least 4 weeks prior to treatment.
- Patients who have received or are receiving inhibitors or inducers of CYP3A4.
- Toxicities (greater than or equal to Common Toxicity Criteria for Adverse Events [CTCAE] Grade 2) caused by previous cancer therapy, excluding alopecia.
- Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the IP until the end of Part A.
- Patients with brain metastases. A scan to confirm the absence of brain metastases is not required.
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of major surgery.
- Patients considered a poor medical risk due to a serious uncontrolled medical disorder, non malignant systemic disease, uncontrolled seizures, or active uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive bilateral interstitial lung disease on high resolution computer tomography (HRCT) scan, or any psychiatric disorder that prohibits obtaining informed consent.
- Patients who have diabetes mellitus.
- Patients who have gastric, gastro-oesophageal, or oesophageal cancer .
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of olaparib.
- Breastfeeding women.
- Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- Patients with known active hepatic disease (eg, hepatitis B or C).
- Patients with a known hypersensitivity to rifampicin or any of the excipients of the product.
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- Resting electrocardiogram (ECG) at screening with measurable QT interval (QT) corrected for heart rate (QTc) greater than 470 msec at 2 or more time points within a 24 hour period or family history of long QT syndrome.
- Concomitant medication contraindicated for use with rifampicin (including, but not limited to): atazanavir, darunavir, fosamprenavir, ritonavir-boosted saquinavir, saquinavir, or tipranavir.
- Patients who have jaundice.
- Patients who weigh less than 50 kg.
- Clinical judgment by the investigator that the patient should not participate in the study.
Who cannot join
None listed.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
About this study
Official title: A Non-randomised, Open-label, Sequential, Multicentre, Two-part, Phase I Study to Assess the Effect of Rifampicin, a CYP Inducer, on the Pharmacokinetics of Olaparib Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours
This is a 2-part study in patients with advanced solid tumours. Part A will investigate the effect of rifampicin on the PK parameters of olaparib in patients; Part B will allow patients continued access to olaparib after the PK phase and will provide additional safety data.
- Conditions
- Solid Tumours
- Being tested
- Pharmacokinetic sampling, Rifampicin, Olaparib tablet dosing
- Keywords
- oncology, cancer, tumour, anticancer drug, pharmacokinetics, olaparib, rifampicin, neoplasm, CYP P450 inducer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pharmacokinetic samplingProcedure or surgery
Blood sampling to measure olaparib, rifampicin and 4β-hydroxycholesterol
RifampicinDrug
Rifampicin (CYP inducer) 600mg taken once daily from Day 5 to Day 14 (Part A)
Olaparib tablet dosingDrug
Olaparib 300mg tablet taken on Days 1 and 14 (Part A). Part B dosing is 300mg olaparib bi-daily
| Study group | Role | What they receive |
|---|---|---|
| Olaparib alone, olaparib+rifampicin | Experimental | Sequential treatments of olaparib alone followed by olaparib+rifampicin, with a washout period inbetween. Receives: Procedure: Pharmacokinetic sampling; Drug: Rifampicin; Drug: Olaparib tablet dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of olaparib by assessment of maximum plasma olaparib concentration (Cmax)
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax). Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC).
Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable.
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable. Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Secondary outcomes (14)
Pharmacokinetics of olaparib by assessment of time to reach maximum plasma concentration for olaparib (tmax).
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of time to reach maximum plasma concentration for olaparib (tmax). Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ).
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ). Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib apparent clearance (CL/F).
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib apparent clearance (CL/F). Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib apparent volume of distribution (Vz/F).
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib apparent volume of distribution (Vz/F). Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib terminal half-life (t1/2).
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of olaparib terminal half-life (t1/2). Olaparib doses are first without, then with rifampicin.
Measured: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of rifampicin by assessment of plasma concentrations of rifampicin during rifampicin dosing period.
Rate and extent of absorption of rifampicin following multiple doses of rifampicin by assessment of plasma concentrations of rifampicin during rifampicin dosing period.
Measured: Rifampicin is dosed daily from Days 5 to 17 in Part A. Blood samples are collected on Days 5, 9, 14 and 17 at 2 hours post rifampicin dose
Demonstration of induction of CYP by assessment of plasma concentrations of 4β-hydroxycholesterol during rifampicin dosing period.
Demonstration of CYP induction by assessment of plasma concentrations of 4β-hydroxycholesterol during rifampicin dosing period.
Measured: Blood samples are collected on Days 5, 9, 14 and 17 at pre-dose of rifampicin in Part A
Assessment of the safety and tolerability of olaparib by collection of adverse event reports
Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Measured: Part A: From baseline, every visit until 30 days after last dose. Part B, from start to 12 months after the last patient has entered Part B
Determine safety and tolerability of olaparib by assessment of 12 lead electrocardiograms
Assessment of standard 12 lead electrocardiograms (ECGs)
Measured: Part A: baseline, Days -1, 17 (and within 30 days post last olaparib dose if not in Part B).
Determine safety and tolerability of olaparib by physical examination
Assessment of physical examination
Measured: Part A: baseline, Day -1 and within 30 days after last dose. Part B: Day 1.
Determine safety and tolerability of olaparib by assessment of vital signs
Assessment of standard vital signs (including blood pressure, pulse)
Measured: Part A: baseline, Days 1,2 and 3. Part B: Days 1,8,15,22,29 then every 4 weeks. Final assessment within 30 days after last dose.
Determine safety and tolerability of olaparib by assessment of clinical chemistry results
Assessment of laboratory parameters (clinical chemistry)
Measured: Part A: baseline, Days -1, 9, 14, 17. Part B: Days 1,8,15,22,29 then every 4 weeks. Final assessment within 30 days after last dose.
Determine safety and tolerability of olaparib by assessment of haematology results
Assessment of laboratory parameters (haematology)
Measured: Part A: baseline, Days -1, 9, 14, 17. Part B: Days 1,8,15,22,29 then every 4 weeks. Final assessment within 30 days after last dose.
Determine safety and tolerability of olaparib by assessment of urinalysis results
Assessment of laboratory parameters (urinalysis)
Measured: Part A: baseline, Days -1, 14, 17. Part B: Day 1 only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2013 (estimated)
- Study startDec 2013
- Primary completionMay 2014
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumoursStudies 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anitra Fielding, Study director, AstraZeneca Senior Research PhysicianLuc Dirix, Principal investigator, GZA Ziekenhuizen Campus Sint-Augustinus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01929603
- Sponsor's protocol ID
- D0816C00008
- Status last verified
- Jan 2017
- First submitted
- 23 Aug 2013
- Last updated
- 16 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Dirix L, Swaisland H, Verheul HM, Rottey S, Leunen K, Jerusalem G, Rolfo C, Nielsen D, Molife LR, Kristeleit R, Vos-Geelen J, Mau-Sorensen M, Soetekouw P, van Herpen C, Fielding A, So K, Bannister W, Plummer R. Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors: Results of Two Phase I Open-label Studies. Clin Ther. 2016 Oct;38(10):2286-2299. doi: 10.1016/j.clinthera.2016.08.010. Epub 2016 Oct 10.
PubMed 27745744
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomised, Open-label, Sequential, Multicentre, Two-part, Phase I Study to Assess the Effect of Rifampicin, a CYP Inducer, on the Pharmacokinetics of Olaparib Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT01929603
- Acronym / sponsor ID
- D0816C00008
- Conditions
- Solid Tumours
- Keywords
- oncology, cancer, tumour, anticancer drug, pharmacokinetics, olaparib, rifampicin, neoplasm, CYP P450 inducer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Dec 2013
- Primary completion
- May 2014 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 28 Aug 2013 (estimated)
- 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.
This is a 2-part study in patients with advanced solid tumours. Part A will investigate the effect of rifampicin on the PK parameters of olaparib in patients; Part B will allow patients continued access to olaparib after the PK phase and will provide additional safety data.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib alone, olaparib+rifampicin | Experimental | Procedure: Pharmacokinetic sampling, Drug: Rifampicin, Drug: Olaparib tablet dosingSequential treatments of olaparib alone followed by olaparib+rifampicin, with a washout period inbetween. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Provision of written informed consent prior to any study-specific procedures.
- Patients aged greater than or equal to 18 years.
- Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
- 4 Patients must have normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below: Haemoglobin (Hb) greater than or equal to 10.0 g/dL, with no blood transfusions in the previous 28 days.
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L. White blood cells (WBC) greater than 3 x 109/L. Platelet count greater than or equal to 100 x 109/L. Total bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN) (except in the case of Gilbert's disease).
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Pharmacokinetic samplingBlood sampling to measure olaparib, rifampicin and 4β-hydroxycholesterol | Procedure or surgery | Olaparib alone, olaparib+rifampicin |
| RifampicinRifampicin (CYP inducer) 600mg taken once daily from Day 5 to Day 14 (Part A) | Drug | Olaparib alone, olaparib+rifampicin |
| Olaparib tablet dosingOlaparib 300mg tablet taken on Days 1 and 14 (Part A). Part B dosing is 300mg olaparib bi-daily | Drug | Olaparib alone, olaparib+rifampicin |
Primary outcome
Pharmacokinetics of olaparib by assessment of maximum plasma olaparib concentration (Cmax)
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax). Olaparib doses are first without, then with rifampicin.
Pharmacokinetics of olaparib by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC). Olaparib doses are first without, then with rifampicin.
Pharmacokinetics of olaparib by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable.
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Rate and extent of absorption of olaparib following single oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable. Olaparib doses are first without, then with rifampicin.
14 secondary outcomes
Pharmacokinetics of olaparib by assessment of time to reach maximum plasma concentration for olaparib (tmax).
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib area under the plasma concentration time curve from zero to the last measurable time point (AUC0-τ).
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib apparent clearance (CL/F).
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib apparent volume of distribution (Vz/F).
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of olaparib by assessment of olaparib terminal half-life (t1/2).
Time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.
Pharmacokinetics of rifampicin by assessment of plasma concentrations of rifampicin during rifampicin dosing period.
Time frame: Rifampicin is dosed daily from Days 5 to 17 in Part A. Blood samples are collected on Days 5, 9, 14 and 17 at 2 hours post rifampicin dose
Demonstration of induction of CYP by assessment of plasma concentrations of 4β-hydroxycholesterol during rifampicin dosing period.
Time frame: Blood samples are collected on Days 5, 9, 14 and 17 at pre-dose of rifampicin in Part A
Assessment of the safety and tolerability of olaparib by collection of adverse event reports
Time frame: Part A: From baseline, every visit until 30 days after last dose. Part B, from start to 12 months after the last patient has entered Part B
Determine safety and tolerability of olaparib by assessment of 12 lead electrocardiograms
Time frame: Part A: baseline, Days -1, 17 (and within 30 days post last olaparib dose if not in Part B).
Determine safety and tolerability of olaparib by physical examination
Time frame: Part A: baseline, Day -1 and within 30 days after last dose. Part B: Day 1.
Determine safety and tolerability of olaparib by assessment of vital signs
Time frame: Part A: baseline, Days 1,2 and 3. Part B: Days 1,8,15,22,29 then every 4 weeks. Final assessment within 30 days after last dose.
Determine safety and tolerability of olaparib by assessment of clinical chemistry results
Time frame: Part A: baseline, Days -1, 9, 14, 17. Part B: Days 1,8,15,22,29 then every 4 weeks. Final assessment within 30 days after last dose.
Determine safety and tolerability of olaparib by assessment of haematology results
Time frame: Part A: baseline, Days -1, 9, 14, 17. Part B: Days 1,8,15,22,29 then every 4 weeks. Final assessment within 30 days after last dose.
Determine safety and tolerability of olaparib by assessment of urinalysis results
Time frame: Part A: baseline, Days -1, 14, 17. Part B: Day 1 only
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2017.
- Derived from this study: PubMed 27745744Dirix L, Swaisland H, Verheul HM, Rottey S, Leunen K, Jerusalem G, Rolfo C, Nielsen D, Molife LR, Kristeleit R, Vos-Geelen J, Mau-Sorensen M, Soetekouw P, van Herpen C, Fielding A, So K, Bannister W, Plummer R. Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors: Results of Two Phase I Open-label Studies. Clin Ther. 2016 Oct;38(10):2286-2299. doi: 10.1016/j.clinthera.2016.08.010. Epub 2016 Oct 10.
- D0816C00008\_Study\_Synopsis\_Redacted.pdfLink provided by the sponsor.
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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.
Anitra Fielding study director
AstraZeneca Senior Research Physician
Luc Dirix principal investigator
GZA Ziekenhuizen Campus Sint-Augustinus
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pharmacokinetic sampling, Rifampicin and Olaparib tablet dosing in people with Solid Tumours, run by AstraZeneca at 5 sites in 2 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 38 inclusion and 0 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: finished, as of the sponsor's last update on 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium, Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pharmacokinetics of olaparib by assessment of maximum plasma olaparib concentration (Cmax) (time frame: Blood samples are collected on olaparib dosing days (Day 1 and 14) at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post olaparib dose Part A.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01929603, which also lists 1 linked publication.
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 16 Jan 2017.