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This is an open-label, single or multiple center study to determine the interaction of rifampin with navitoclax (ABT-263) in approximately 12 subjects with cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (navitoclax and rifampin) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| navitoclax | Drug | Subjects will be dosed with Navitoclax, then dosed with Navitoclax in combination with Rifampin. |
|
| Measure | Description | Time Frame |
|---|---|---|
| To determine the effect of rifampin on the pharmacokinetics of navitoclax. | Weekly |
| Measure | Description | Time Frame |
|---|---|---|
| To determine the safety of navitoclax when administered alone and in combination with rifampin in these patients. | Daily |
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Inclusion Criteria
Exclusion Criteria
Subjects with brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug.
History of or is clinically suspicious for cancer-related central nervous system (CNS) disease.
Has undergone an allogeneic stem cell transplant.
Has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding.
Has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
Has active immune thrombocytopenic purpura or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).
Significant history of cardiovascular disease (e.g., MI, thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease. Female subject is pregnant or breast-feeding.
History of or an active medical condition(s) that affects absorption or motility (e.g., Crohn's disease, celiac disease, gastroparesis, short bowel syndrome, etc).
Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for hypothyroidism or estrogen replacement therapy [ERT], or agonists required to suppress serum testosterone levels [e.g., LHRH, GnRH, etc.] for subjects with prostate cancer Subject is currently receiving or requires anticoagulation therapy (e.g., warfarin at any dose) or any drugs or herbal supplements that affect platelet function, with the exception of low-dose heparin used to maintain the patency of a catheter.
Subject has used known inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin and carbamazepine) of cytochrome P450 3A (CYP3A) within 1 week prior to first dose of study.
Subject has a history of hypersensitivity to any of the rifamycins.
In the opinion of the Investigator, the subject is an unsuitable candidate to receive ABT-263.
History of or is clinically suspicious for cancer-related central nervous system (CNS) disease.
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25047139 | Result | Yang J, Pradhan RS, Rosen LS, Graham AM, Holen KD, Xiong H. Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer. J Clin Pharm Ther. 2014 Dec;39(6):680-4. doi: 10.1111/jcpt.12193. Epub 2014 Jul 22. |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| C528561 | navitoclax |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifampin | Drug | Subjects will be dosed with Navitoclax, then, dosed with Navitoclax in combination with Rifampin. |
|
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |