Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Olaparib tablet dosing
Olaparib dosing · 4 trials · 1 indication
Summary of Geometric Least Squares (GLS) Mean for normal, mild and moderate hepatic impairment
Summary of ratio of Geometric Least Squares (GLS) Means
Summary of Geometric Least Squares (GLS) Mean
Summary of Ratio of Geometric Least Squares (GLS) Means
Summary of Geometric Least Squares (GLS) Mean for ratio of mild hepatic impairment compared to normal
Summary of Ratio of Geometric Least Squares (GLS) Means
Summary of Geometric Least Squares (GLS) Means
Summary of Ratio of Geometric Least Squares (GLS) Means
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.
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.
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.
Maximum plasma drug concentration of olaparib
Area under plasma concentration-time curve from zero to infinity of olaparib
Area under plasma concentration-time curve from zero to the last measurable time point of olaparib
Time to reach maximum plasma concentration of olaparib
Apparent volume of distribution of olaparib
Apparent plasma clearance of olaparib
Renal clearance of olaparib, calculated as the ratio of amount of drug excreted over 24 hours to AUC0-24
Terminal half-life of olaparib
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)
| Arm | Type | Description |
|---|---|---|
| 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 |
| Mild hepatic impairment | OTHER | As defined by the Child-Pugh Classification System. |
| Moderate hepatic impairment | OTHER | As defined by the Child-Pugh Classification System. |
| Olaparib alone, olaparib+rifampicin | EXPERIMENTAL | Sequential treatments of olaparib alone followed by olaparib+rifampicin, with a washout period inbetween. |
| Normal renal function | OTHER | Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). |
| Mild renal impairment | OTHER | Patients with calculated serum creatinine clearance 51-80 mL/min (using Cockcroft-Gault equation). |
| Moderate renal impairment | OTHER | Patients with calculated serum creatinine clearance 31-50 mL/min (using Cockcroft-Gault equation). |
| Olaparib alone, olaparib+itraconozole | EXPERIMENTAL | Sequential treatments of olaparib alone followed by olaparib+itraconazole, with a washout period in between. |
| Name | Type | Description |
|---|---|---|
| Olaparib tablet dosing | DRUG | Part A - single 300mg oral dose olaparib (administered as 2x150mg tablets) Part B - 300mg oral dose olaparib (administered as 2x150mg tablets) bd |
| Pharmacokinetic sampling | PROCEDURE | Blood sampling to measure olaparib, rifampicin and 4β-hydroxycholesterol |
| Rifampicin | DRUG | Rifampicin (CYP inducer) 600mg taken once daily from Day 5 to Day 14 (Part A) |
| Itraconazole | DRUG | Itraconazole 200mg od Part A days 5 to 11 only |
Inclusion criteria:- For inclusion in the study as a patient with hepatic impairment, the following criterion must be met: 1. 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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
Olaparib tablet dosing refers to the oral tablet formulation of olaparib studied in Phase 1 pharmacokinetic trials in patients with advanced solid tumours. These trials examined how the tablet is absorbed and processed under different conditions, including co-administration with other drugs and in patients with impaired kidney or liver function.
Olaparib targets PARP1, PARP2, and PARP3, a family of enzymes involved in DNA repair. It acts as an inhibitor of these targets. By inhibiting PARP enzymes, olaparib interferes with the DNA repair process in tumour cells, which is the basis of its investigation in advanced solid tumours.
Olaparib is developed by AstraZeneca PLC, which trades under the ticker AZN. The company sponsored the Phase 1 clinical trials evaluating olaparib tablet dosing in patients with advanced solid tumours.
Olaparib tablet dosing has been studied in Phase 1 clinical trials. Four Phase 1 trials in advanced solid tumours have been completed, with no active trials ongoing. The trials enrolled a total of 204 patients across multiple countries including Belgium, the Netherlands, the United Kingdom, Denmark, France, and South Korea.
Four completed Phase 1 trials evaluated olaparib tablet dosing: NCT01929603 assessed the effect of rifampicin on olaparib blood levels; NCT01900028 examined itraconazole's effect on olaparib pharmacokinetics and QT interval; NCT01894256 studied olaparib in patients with normal or impaired kidney function; and NCT01894243 assessed olaparib in patients with normal liver function or mild to moderate liver impairment.
Yes, Olaparib tablet dosing is an alternative name for olaparib when referring to the oral tablet formulation. The Phase 1 trials listed under this name investigated the pharmacokinetics, safety, and drug interaction profile of the olaparib tablet in patients with advanced solid tumours.