Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01894243 | 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 | PHASE1 | COMPLETED | 31 | — | — | Mar 13, 2014 | Mar 30, 2017 | Sep 13, 2019 | 12 | Czechia, France +3 |
| NCT01894256 | Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal or Impaired Kidney Function | PHASE1 | COMPLETED | 56 | — | — | Nov 1, 2013 | Feb 1, 2016 | Oct 13, 2016 | 13 | Belgium, Denmark +3 |
| NCT01900028 | To Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of Olaparib, and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation to Patients With Advanced Solid Tumours | PHASE1 | COMPLETED | 85 | — | — | Oct 1, 2013 | Sep 1, 2016 | Oct 17, 2016 | 14 | Belgium, Denmark +2 |
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
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 maximum plasma 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 area under the plasma concentration 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 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. |
| 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 samples taken pre and post dosing with olaparib+/- itraconazole |
| 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 | 2 | PHASE2 | pembrolizumab, V503, GARDASIL |
| Incyte Corporation | INCY | 1 | PHASE2 | Chemotherapy, Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115, pembrolizumab |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | E7 TCR-T cells, Aldesleukin |
| AstraZeneca PLC | AZN | 1 | — | Trastuzumab deruxtecan |