Solid TumoursPhase 1NCT01894243

Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment

A Phase 1 study testing Olaparib tablet dosing in people with Solid Tumours, run by AstraZeneca at 12 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a 2-part study in patients with advanced solid tumours. Part A will investigate the PK of olaparib in patients with mild or moderate hepatic impairment compared to patients with normal hepatic function; Part B will allow patients with mild or moderate hepatic impairment or normal hepatic function continued… 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 tablet dosing
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 12 sitesin 5 countries
Study dates: 13 Mar 2014to 30 Mar 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 as a patient with hepatic impairment, the following criterion must be met:
Patients must have stable mild hepatic impairment (as defined by Child-Pugh classification), for at least 1 month prior to the start of the study or stable moderate hepatic impairment ( as defined by Child Pugh classification) for at least 2 weeks prior to the start of the study. Patients with hepatic metastases and/or HCC are eligible for the study, providing the hepatic metastases or HCC are not the sole reason for any changes in liver function satisfying the criteria for mild or moderate hepatic impairment as defined by the Child Pugh criteria. Patients must have globally impaired hepatic function to participate in the study. For inclusion in the study as a patient with normal hepatic function, the following criteria must be met:
Negative result for serum hepatitis B surface antigen and hepatitis C antibody.
Total bilirubin less than or equal to1.5 x institutional upper limit of normal (ULN), albumin and prothrombin time within normal limits and must not have ascites (unless related to disease under study) or encephalopathy.
Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (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. All patients must fulfil the following criteria:
Provision of written informed consent prior to any study specific procedures.

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Patients must be greater than or equal to18 years of age.
Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists. In case of HCC, histological or cytological confirmation is not required in the following situations, as per international guidelines of the scientific societies European Society for Medical Oncology (ESMO) and
American Association for the Study of Liver Diseases (AASLD):
Nodules >2 cm with a typical feature of HCC on a dynamic imaging technique, or any nodule associated with α-fetoprotein (AFP) concentration >400 ng/ml or rising AFP on sequential determinations, do not require biopsy but should be considered as proven HCC (Jelic et al 2010).
Nodules >1 cm found on ultrasound screening of a cirrhotic liver should be investigated further with either 4-phase multi-detector CT scan or dynamic contrast enhanced MRI. If the appearances are typical of HCC (ie, hyper-vascular in the arterial phase with washout in the portal venous or delayed phase), the lesion should be treated as HCC. If the findings are not characteristic or the vascular profile is not typical, a second contrastenhanced study with the other imaging modality should be performed, or the lesion should be biopsied (level II) (Bruix et al 2011).
Normal organ and bone marrow function measured within 28 days prior to administration of IP as defined below: Haemoglobin greater than or equal to 9.0 g/dL, with no blood transfusions in the previous 28 days.
Absolute neutrophil count (ANC) greater than or equal to1.5 x 109/L. White blood cells (WBC) greater than 3 x 109/L. Platelet count greater than or equal to 75 x 109/L. Serum creatinine less than or equal to1.5 x institutional ULN.
Calculated serum creatinine clearance greater than 50 mL/min (using Cockcroft-Gault formula or by 24-hour urine collection).
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Patients must have a life expectancy greater than or equal to 8 weeks.
Evidence of non childbearing status for women of childbearing potential, or postmenopausal 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 postmenopausal 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).
Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
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 both AstraZeneca staff, its agents and/or staff at the study site).
Previous enrolment in the present study.
Treatment with any investigational product (IP) during the last 14 days (or a longer period depending on the defined characteristics of the agent used).
Treatment in the previous 3 months before dosing in this study with any drug known to have a well defined potential for hepatoxicity (eg, halothane).
Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment. 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 within the washout period.

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Toxicities (greater than or equal to CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
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 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 with a history of heart failure or left ventricular dysfunction.
2. Patients who have gastric, gastro-oesophageal or oesophageal cancer. 13. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of olaparib.
14. Breastfeeding women. 15. Immunocompromised patients eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
16. Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 17. Resting ECG with measurable QTc greater than 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
18. Clinical judgment by the investigator that the patient should not participate in the study. In addition to exclusion criteria 1 to 18, patients with normal hepatic function should not enter the study if the following exclusion criterion is fulfilled: 19. History or presence of hepatic disease known to interfere with the absorption, distribution, metabolism or excretion of olaparib. In addition to exclusion criteria 1 to 18, patients with mild or moderate hepatic impairment should not enter the study if the following exclusion criteria are fulfilled: 20. Patients with hepatic encephalopathy (as described in the Child Pugh Classification system).
21. Fluctuating or rapidly deteriorating hepatic function as indicated by widely varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period (eg, advanced ascites, fever, active gastrointestinal bleeding).
22. Change in dose regimen of medically required medication within the last 2 weeks before screening and/or the use of disallowed co-medication in the 3 weeks prior to admission to the clinic.
23. Presence of acute liver disease caused by drug toxicity or by an infection. 24. Severe portal hypertension or surgical porto-systemic shunts. 25. Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
26. Oesophageal variceal bleeding within the past 2 months. 27. Anticoagulant therapy with warfarin or related coumarins.

Trial locations and contacts

12 sites in 5 countries.

Country

City, postcode or hospital

12 sites in 5 countries

France6 sites

Research Site
Bordeaux, 33075
Research Site
Bordeaux, 33076
Research Site
Dijon, 21079
Research Site
Grenoble, 38043
Research Site
Lyon, 69373
Research Site
Paris, 75651

Other trials in France

Netherlands2 sites

Research Site
Amsterdam, 1066 CX
Research Site
Maastricht, 6202 AZ

Other trials in Netherlands

United Kingdom2 sites

Research Site
London
Research Site
Sutton, SM2 5PT

Other trials in United Kingdom

Czechia1 site

Research Site
Brno, 656 53

Other trials in Czechia

South Korea1 site

Research Site
Seoul, 06591

Other trials in South Korea

About this study

Official title: An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study to Determine the Pharmacokinetics, Safety and Tolerability of Olaparib Following a Single Oral 300 mg Dose to Patients With Advanced Solid Tumours and Normal Hepatic Function or Mild or Moderate Hepatic Impairment

Conditions: Solid Tumours
Being tested: Olaparib tablet dosing
Keywords: oncology,, cancer,, neoplasm,, anticancer drug,, pharmacokinetics,, area under curve,, olaparib,, solid tumour,, mild hepatic impairment,, moderate hepatic impairment
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Olaparib tablet dosingDrug
Part A - single 300mg oral dose olaparib (administered as 2x150mg tablets) Part B - 300mg oral dose olaparib (administered as 2x150mg tablets) bd

Study groups in NCT01894243
Study group	Role	What they receive
Normal hepatic function	Other	Patients with: (i) negative result for serum hepatitis B surface antigen and hepatitis C antibody (ii) total bilirubin ≤1.5 x institutional upper limit of normal (ULN), albumin and prothrombin time within normal limits and must not have ascites (unless related to disease under study) or encephalopathy (iii) aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (ALT) ≤2.5 x institutional ULN unless liver metastases are present in which case it must be ≤5 x ULN Receives: Drug: Olaparib tablet dosing
Mild hepatic impairment	Other	As defined by the Child-Pugh Classification System. Receives: Drug: Olaparib tablet dosing
Moderate hepatic impairment	Other	As defined by the Child-Pugh Classification System. Receives: Drug: Olaparib tablet dosing

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Plasma Concentration (Cmax)
Summary of Geometric Least Squares (GLS) Mean for normal, mild and moderate hepatic impairment
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal
Summary of ratio of Geometric Least Squares (GLS) Means
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC)
Summary of Geometric Least Squares (GLS) Mean
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Ratio of Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC) - Mild vs Normal and Moderate vs Normal
Summary of Ratio of Geometric Least Squares (GLS) Means
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)
Summary of Geometric Least Squares (GLS) Mean for ratio of mild hepatic impairment compared to normal
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Ratio of Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)
Summary of Ratio of Geometric Least Squares (GLS) Means
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Apparent Clearance Following Oral Administration (CL/F)
Summary of Geometric Least Squares (GLS) Means
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Ratio of Apparent Clearance Following Oral Administration (CL/F)
Summary of Ratio of Geometric Least Squares (GLS) Means
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Time to Reach Maximum Plasma Concentration (Tmax)
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Terminal Half-life (t½)
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Apparent Volume of Distribution (Vz/F)
Measured: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Mar 201430 Mar 2017

First posted10 Jul 2013 (estimated)
Study start13 Mar 2014
Primary completion29 Nov 2016
Study completion30 Mar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01894243
Sponsor's protocol ID: D0816C00005
Other IDs: 2013-002246-37
Status last verified: Jul 2019
First submitted: 4 Jul 2013
Last updated: 13 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
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All Solid Tumours trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study to Determine the Pharmacokinetics, Safety and Tolerability of Olaparib Following a Single Oral 300 mg Dose to Patients With Advanced Solid Tumours and Normal Hepatic Function or Mild or Moderate Hepatic Impairment
ClinicalTrials.gov ID: NCT01894243
Acronym / sponsor ID: D0816C00005
Conditions: Solid Tumours
Keywords: oncology,, cancer,, neoplasm,, anticancer drug,, pharmacokinetics,, area under curve,, olaparib,, solid tumour,
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 13 Mar 2014 (actual)
Primary completion: 29 Nov 2016 (actual)
Study completion: 30 Mar 2017 (actual)
First posted: 10 Jul 2013 (estimated)
Results: Posted 13 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Normal hepatic function	Other	Drug: Olaparib tablet dosingPatients with: (i) negative result for serum hepatitis B surface antigen and hepatitis C antibody (ii) total bilirubin ≤1.5 x institutional upper limit of normal (ULN), albumin and prothrombin time within normal limits and must not have ascites (unless related to disease under study) or encephalopathy (iii) aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (ALT) ≤2.5 x institutional ULN unless liver metastases are present in which case it must be ≤5 x ULN
Mild hepatic impairment	Other	Drug: Olaparib tablet dosingAs defined by the Child-Pugh Classification System.
Moderate hepatic impairment	Other	Drug: Olaparib tablet dosingAs defined by the Child-Pugh Classification System.

Who may qualify

Ages: 18 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

For inclusion in the study as a patient with hepatic impairment, the following criterion must be met:
Patients must have stable mild hepatic impairment (as defined by Child-Pugh classification), for at least 1 month prior to the start of the study or stable moderate hepatic impairment ( as defined by Child Pugh classification) for at least 2 weeks prior to the start of the study. Patients with hepatic metastases and/or HCC are eligible for the study, providing the hepatic metastases or HCC are not the sole reason for any changes in liver function satisfying the criteria for mild or moderate hepatic impairment as defined by the Child Pugh criteria. Patients must have globally impaired hepatic function to participate in the study. For inclusion in the study as a patient with normal hepatic function, the following criteria must be met:
Negative result for serum hepatitis B surface antigen and hepatitis C antibody.
Total bilirubin less than or equal to1.5 x institutional upper limit of normal (ULN), albumin and prothrombin time within normal limits and must not have ascites (unless related to disease under study) or encephalopathy.
Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (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. All patients must fulfil the following criteria:

Key exclusion criteria (19 listed)

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents and/or staff at the study site).
Previous enrolment in the present study.
Treatment with any investigational product (IP) during the last 14 days (or a longer period depending on the defined characteristics of the agent used).
Treatment in the previous 3 months before dosing in this study with any drug known to have a well defined potential for hepatoxicity (eg, halothane).
Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment. 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.

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 tablet dosingPart A - single 300mg oral dose olaparib (administered as 2x150mg tablets) Part B - 300mg oral dose olaparib (administered as 2x150mg tablets) bd	Drug	Mild hepatic impairment, Moderate hepatic impairment, Normal hepatic function

Primary outcome

Maximum Plasma Concentration (Cmax)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Geometric Least Squares (GLS) Mean for normal, mild and moderate hepatic impairment
Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of ratio of Geometric Least Squares (GLS) Means
Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Geometric Least Squares (GLS) Mean
Ratio of Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC) - Mild vs Normal and Moderate vs Normal
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Ratio of Geometric Least Squares (GLS) Means
Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Geometric Least Squares (GLS) Mean for ratio of mild hepatic impairment compared to normal
Ratio of Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Ratio of Geometric Least Squares (GLS) Means
Apparent Clearance Following Oral Administration (CL/F)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Geometric Least Squares (GLS) Means
Ratio of Apparent Clearance Following Oral Administration (CL/F)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Summary of Ratio of Geometric Least Squares (GLS) Means
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Terminal Half-life (t½)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Apparent Volume of Distribution (Vz/F)
Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.

Results and safety

Results posted to the registry on 13 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Hepatic Function	13	0
Mild Hepatic Impairment	10	0
Moderate Hepatic Impairment	8	0

Primary outcome: Maximum Plasma Concentration (Cmax)

Time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.. Geometric least squares mean (90% Confidence Interval). Unit: μg/mL

Measure	Normal Hepatic Function n = 13	Mild Hepatic Impairment n = 9	Moderate Hepatic Function n = 8
Value	7.32 (5.95 to 9.00)	8.25 (6.43 to 10.58)	6.40 (4.92 to 8.34)

Population analysed: PK Analysis Set (Part A) One patient excluded from mild impairment arm due to surgery that may affect olaparib absorption.

Primary outcome: Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal

Measure	GLSMean Ratio of Mild to Normal n = 22	GLSMean Ratio of Moderate to Normal n = 21
Value	1.13 (0.82 to 1.56)	0.87 (0.63 to 1.22)

Population analysed: PK Analysis Set (Part A) One patient excluded from mild impairment group due to surgery that may affect olaparib absorption.

Primary outcome: Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC)

Measure	Normal Hepatic Function n = 13	Mild Hepatic Impairment n = 9	Moderate Hepatic Impairment n = 8
Value	52.33 (38.88 to 70.43)	60.25 (42.17 to 86.10)	56.29 (38.55 to 82.20)

Population analysed: PK Analysis Set (Part A) One patient excluded from mild impairment group due to surgery that may affect olaparib absorption.

Primary outcome: Ratio of Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC) - Mild vs Normal and Moderate vs Normal

Measure	GLSMean Ratio of Mild to Normal n = 22	GLSMean Ratio of Moderate to Normal n = 21
Value	1.15 (0.72 to 1.83)	1.08 (0.66 to 1.74)

Population analysed: PK Analysis Set (Part A) One patient excluded from mild impairment group due to surgery that may affect olaparib absorption.

Adverse events

Time frame: Onset date between the date of first dose in Part A and the day before first dose in Part B, or 30 days following the date of last dose of study medication if the subject has discontinued in Part A. For Part B, onset date on or after the first dose in Part B, and up to (and including) 30 days after the last dose date in the study.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal (Part A)	1 of 13 (7.7%)	10 of 13 (76.9%)	0 of 13
Mild (Part A)	0 of 10 (0%)	3 of 10 (30%)	0 of 10
Moderate (Part A)	1 of 8 (12.5%)	5 of 8 (62.5%)	0 of 8
Normal (Part B)	3 of 13 (23.1%)	13 of 13 (100%)	1 of 13
Mild (Part B)	3 of 10 (30%)	10 of 10 (100%)	1 of 10
Moderate (Part B)	4 of 8 (50%)	7 of 8 (87.5%)	4 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Malignant Solid Neoplasm

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

Christian Rolfo principal investigator

UZ Antwerpen

12 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Olaparib tablet dosing in people with Solid Tumours, run by AstraZeneca at 12 sites in 5 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 23 inclusion and 19 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 13 Sep 2019. 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 France, Netherlands, United Kingdom, Czechia, South Korea. 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?

Yes. Results are posted in the registry (first posted 13 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Plasma Concentration (Cmax) (time frame: Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.). The study lists 11 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 NCT01894243.

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 13 Sep 2019.