Solid TumoursPhase 1NCT01921140
To Determine the Effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours
A Phase 1 study testing Olaparib tablets, Pharmacokinetic sampling and Dietary Fasted in people with Solid Tumours, run by AstraZeneca at 12 sites in 4 countries.
Trial summary
This is a 3 part study for patients with solid tumours. The purpose of Part A is to measure the amount of olaparib or its breakdown products in the bloodstream for up to 72 hours after eating and the effect of olaparib on QT interval following a single oral dose of olaparib tablets. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Solid Tumours
- What is being tested?
- Olaparib tablets, Pharmacokinetic sampling and Dietary Fasted
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 24 Sep 2013to 15 Mar 2022
- 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 130 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.
- Able to eat a high-fat meal within a 30-minute period, as provided by the study site.
- Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
- Normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below:
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- Haemoglobin 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.
- 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 5 x ULN.
- Serum creatinine less than or equal to 1.5 x institutional ULN. Serum potassium, sodium, magnesium and calcium within the institutional normal range.
- Calculated serum creatinine clearance greater than 50 mL/min (using Cockroft-Gault formula or by 24-hour urine collection).
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. 8. Patients must have a life expectancy of greater than or equal to 16 weeks.
- 9. 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 the first treatment period in Part A. Postmenopausal 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). 10. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- 11. 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 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab, and corticosteroids, which should be stable for at least 4 weeks prior to start of olaparib dosing.
Who cannot join
- 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 CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
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- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with asymptomatic brain metastases or with symptomatic but stable brain metastases can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment.
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
- Patients unable to fast for up to 14 hours.
- 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 computed tomography (HRCT) scan, or any psychiatric disorder that prohibits obtaining informed consent.
- Patients with a history of poorly controlled hypertension with resting blood pressure (BP) greater than 150/100 mm Hg in the presence or absence of a stable regimen of hypertensive therapy. Measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minute intervals and averaged. If the first 2 diastolic readings differ by more than 5 mm Hg, an additional reading should be obtained and averaged.
- Patients with a history of heart failure or left ventricular dysfunction, and patients who require calcium channel blockers.
- Patients with type I or type II diabetes.
- 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 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 (ie, hepatitis B or C).
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 20. Mean QTc with Fridericia's correction (QTcF) greater than 470 ms in screening ECG or history of familial long QT syndrome:
- A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval greater than 470 ms).
- A history of additional risk factors for Torsade de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
- 21. The use of concomitant medications that prolong the QT/QTc interval. 22. Clinical judgment by the investigator that the patient should not participate in the study
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
United Kingdom4 sites
Research Site
London, SE1 9RT
Research Site
Manchester, M20 4BX
Research Site
Newcastle upon Tyne, NE7 7DN
Research Site
Surrey, SM1 2DL
Belgium3 sites
Research Site
Brussels, 1090
Research Site
Leuven, 3000
Research Site
Liège, 4000
Netherlands3 sites
Research Site
Maastricht, 6202 AZ
Research Site
Nijmegen, 6525 GA
Research Site
Utrecht, 3584 CX
About this study
Official title: A Randomised, Open-label, Three-part, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of Olaparib and to Provide Data on the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours
This is a 3 part study for patients with solid tumours. The purpose of Part A is to measure the amount of olaparib or its breakdown products in the bloodstream for up to 72 hours after eating and the effect of olaparib on QT interval following a single oral dose of olaparib tablets. Part B will determine the effect of olaparib on the QT interval following multiple oral dosing. Part C will allow patients continued access to olaparib tablets and will provide additional safety data collection.
- Conditions
- Solid Tumours
- Being tested
- Olaparib tablets, Pharmacokinetic sampling, Dietary Fasted, Dietary High Fat
- Keywords
- Oncology, cancer, tumour, neoplasm, anticancer drug, food, area under the curve, pharmacokinetics, olaparib, neoplasm, metabolites, QT interval effects
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olaparib tabletsDrug
Olaparib dosing (2X 150mg tablets) following allocated meal
Pharmacokinetic samplingProcedure or surgery
Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet
Dietary FastedOther
2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period
Dietary High FatOther
2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period.
| Study group | Role | What they receive |
|---|---|---|
| Fasted | Other | Olaparib tablets following no breakfast Receives: Drug: Olaparib tablets; Procedure: Pharmacokinetic sampling; Other: Dietary Fasted |
| High-fat meal | Other | Olaparib tablets after high-fat breakfast Receives: Drug: Olaparib tablets; Procedure: Pharmacokinetic sampling; Other: Dietary High Fat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of olaparib: area under the plasma-time curve from zero to infinity (AUC)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib:maximum olaparib concentration (Cmax)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax)
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib: area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable (AUC0-t)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) 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.
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib time to reach maximum plasma concentration for olaparib (tmax)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of time to reach maximum plasma concentration for olaparib (tmax)
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib olaparib apparent clearance (CL/F)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent clearance (CL/F)
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib:apparent volume of distribution (Vz/F)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent volume of distribution (Vz/F)
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib :terminal rate constant (λz)
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of terminal rate constant (λz)
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Pharmacokinetics of olaparib:terminal half-life (t1/2).
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib terminal half-life (t1/2).
Measured: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Secondary outcomes (3)
Assessment of electrocardiogram (ECG) intervals (including QT and QTc interval)
The QT interval uncorrected and corrected for heart rate (QTc) following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation.
Measured: Digital ECG's will be recorded at Day-1, Day 1 of both treatment periods in Part A at: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post olaparib dose. Part B Day -1 & Day 5: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
To assess the safety and tolerability of olaparib following oral dosing
Adverse events (AEs) will be collected from the time of signed informed consent throughout the treatment period in Part A and Part B up to and including the 30-day follow-up period. In Part C, AEs will be collected until 12 months after the last patient entered Part C, and including the 30 day follow-up period for any patients who discontinue.
Assessment of AEs, graded by CTCAE (v4.03),
Measured: Part A&B: Adverse events (AEs) will be collected from the time of signed informed consent up to and including the 30-day follow-up period. In Part C, AEs will be collected for 12 months
To assess safety and tolerability of oral olaparib dosing
Assessment of AEs, graded by CTCAE (v4.0), physical examination, vital signs (including BP and pulse), standard 12-lead ECG and evaluation of laboratory parameters (clinical chemistry, haematology, and urinalysis). Assessment of physical examination, vital signs, ECG and evaluation of laboratory parameters will occur at screening, on the day before dosing in each treatment period and 30 days after last dose in Parts A and B. In Part C, all except ECG will be assessed weekly for a 28-day period followed by every 4 weeks up to 12 months after the last patient enters Part C and at treatment discontinuation. All will be assessed 30 days after last dose.
Measured: Laboratory and vital sign assessments will be carried out at baseline and then at every scheduled visit until 30 days post last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2013 (estimated)
- Study start24 Sep 2013
- Primary completion8 Apr 2014
- Study completion15 Mar 2022
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
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anitra Fielding, Study director, AstraZeneca Sponsor Research PhysicianRuth Plummer, Prof, Principal investigator, Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01921140
- Sponsor's protocol ID
- D0816C00004
- Status last verified
- Nov 2022
- First submitted
- 12 Jul 2013
- Last updated
- 22 Nov 2022
- Results posted
- No
- Data monitoring committee
- 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. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Plummer R, Swaisland H, Leunen K, van Herpen CM, Jerusalem G, De Greve J, Lolkema MP, Soetekouw P, Mau-Sorensen M, Nielsen D, Spicer J, Fielding A, So K, Bannister W, Molife LR. Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours. Cancer Chemother Pharmacol. 2015 Oct;76(4):723-9. doi: 10.1007/s00280-015-2836-2. Epub 2015 Aug 5.
PubMed 26242220
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open-label, Three-part, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of Olaparib and to Provide Data on the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT01921140
- Acronym / sponsor ID
- D0816C00004
- Conditions
- Solid Tumours
- Keywords
- Oncology, cancer, tumour, neoplasm, anticancer drug, food, area under the curve, pharmacokinetics, olaparib, neoplasm, metabolites, QT interval effects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 24 Sep 2013 (actual)
- Primary completion
- 8 Apr 2014 (actual)
- Study completion
- 15 Mar 2022 (actual)
- First posted
- 13 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 3 part study for patients with solid tumours. The purpose of Part A is to measure the amount of olaparib or its breakdown products in the bloodstream for up to 72 hours after eating and the effect of olaparib on QT interval following a single oral dose of olaparib tablets. Part B will determine the effect of olaparib on the QT interval following multiple oral dosing. Part C will allow patients continued access to olaparib tablets and will provide additional safety data collection.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fasted | Other | Drug: Olaparib tablets, Procedure: Pharmacokinetic sampling, Other: Dietary FastedOlaparib tablets following no breakfast |
| High-fat meal | Other | Drug: Olaparib tablets, Procedure: Pharmacokinetic sampling, Other: Dietary High FatOlaparib tablets after high-fat breakfast |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Provision of written informed consent prior to any study specific procedures.
- Patients aged greater than or equal to 18 years.
- Able to eat a high-fat meal within a 30-minute period, as provided by the study site.
- Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
- Normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below:
Key exclusion criteria (22 listed)
- 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.
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 |
|---|---|---|
| Olaparib tabletsOlaparib dosing (2X 150mg tablets) following allocated meal | Drug | Fasted, High-fat meal |
| Pharmacokinetic samplingBlood samples taken pre and post dosing with 2x 150 mg olaparib tablet | Procedure or surgery | Fasted, High-fat meal |
| Dietary Fasted2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period | Other | Fasted |
| Dietary High Fat2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period. | Other | High-fat meal |
Primary outcome
Pharmacokinetics of olaparib: area under the plasma-time curve from zero to infinity (AUC)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
Pharmacokinetics of olaparib:maximum olaparib concentration (Cmax)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of maximum plasma olaparib concentration (Cmax)
Pharmacokinetics of olaparib: area under the plasma concentration time curve from zero to the last measurable time point, AUC0-t, if AUC is not adequately estimable (AUC0-t)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) 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.
Pharmacokinetics of olaparib time to reach maximum plasma concentration for olaparib (tmax)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of time to reach maximum plasma concentration for olaparib (tmax)
Pharmacokinetics of olaparib olaparib apparent clearance (CL/F)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent clearance (CL/F)
Pharmacokinetics of olaparib:apparent volume of distribution (Vz/F)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib apparent volume of distribution (Vz/F)
Pharmacokinetics of olaparib :terminal rate constant (λz)
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of terminal rate constant (λz)
Pharmacokinetics of olaparib:terminal half-life (t1/2).
Time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
Rate and extent of absorption of olaparib following single (Part A) and multiple (Part B) oral doses of olaparib tablet formulation by assessment of olaparib terminal half-life (t1/2).
3 secondary outcomes
Assessment of electrocardiogram (ECG) intervals (including QT and QTc interval)
Time frame: Digital ECG's will be recorded at Day-1, Day 1 of both treatment periods in Part A at: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post olaparib dose. Part B Day -1 & Day 5: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.
To assess the safety and tolerability of olaparib following oral dosing
Time frame: Part A&B: Adverse events (AEs) will be collected from the time of signed informed consent up to and including the 30-day follow-up period. In Part C, AEs will be collected for 12 months
To assess safety and tolerability of oral olaparib dosing
Time frame: Laboratory and vital sign assessments will be carried out at baseline and then at every scheduled visit until 30 days post last dose
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 22 Nov 2022.
- Derived from this study: PubMed 26242220Plummer R, Swaisland H, Leunen K, van Herpen CM, Jerusalem G, De Greve J, Lolkema MP, Soetekouw P, Mau-Sorensen M, Nielsen D, Spicer J, Fielding A, So K, Bannister W, Molife LR. Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours. Cancer Chemother Pharmacol. 2015 Oct;76(4):723-9. doi: 10.1007/s00280-015-2836-2. Epub 2015 Aug 5.
- D0816C00004\_Study\_Synopsis\_Redacted.pdfLink provided by the sponsor.
- D0816C00004\_food\_effect\_tablet\_protocol\_redacted\_SECURELink provided by the sponsor.
- 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. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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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 Sponsor Research Physician
Ruth Plummer, Prof principal investigator
Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaparib tablets, Pharmacokinetic sampling and Dietary Fasted in people with Solid Tumours, run by AstraZeneca at 12 sites in 4 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 16 inclusion and 22 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 22 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom, Belgium, Netherlands, Denmark. 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: area under the plasma-time curve from zero to infinity (AUC) (time frame: Blood samples will be collected in both treatment periods of Part A: pre-dose, 0.25, 0.5, 1, 1.5 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post olaparib dose. In Part B Day -1 and Day 5: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, & 12 hours post dose.). The study lists 8 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 NCT01921140, 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 22 Nov 2022.