Clinical trial NCT00743028: Assess the Oral Bioavailability of New ABT-263 Formulations
Official title: A Single Dose Study Evaluating the Oral Bioavailability and Pharmacokinetics of the Capsule Formulation of ABT-263 in Subjects With Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Lymphomas
Leukemias
Keywords: Other hematological and non-hematological malignancies
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2008-08-28
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multicenter crossover study to determine the oral bioavailability of new ABT-263 formulations relative to that of the current ABT-263 formulation being administered in ongoing Phase 1/2a studies. Approximately 36 evaluable subjects with lymphoid malignancies, including chronic lymphocytic leukemia, and solid tumors will be enrolled in this study.


Eligibility criteria: Inclusion Criteria:

* \> or =18 years of age;
* Non-hematologic malignancy or hematologic malignancy that is either relapsed or refractory to standard therapy, or failed up to 5 prior standard therapies or no know effective therapy exists;
* Life expectancy is at least 90 days;
* If clinically indicated, (e.g., subjects over the age of 70) subjects must have documented brain imaging (MRI or CT) negative for subdural or epidural hematoma within 28 days prior to the 1st dose of study drug;
* ECOG performance score of \< or = 1;
* Adequate bone marrow, renal and hepatic function per local laboratory reference range as follows:

  * ANC \> or = 1,000/µl;
  * Platelets \> or = 100,000/mm3;
  * Hemoglobin \> or = 9.0 g/dL;
  * serum creatinine \< or = 2.0 mg/dL or calculated creatinine clearance \> or = 50;
* AST and ALT \< or = 3.0 x ULN; Bilirubin \< or = 1.5 x ULN. Gilbert's Syndrome may have a Bilirubin \> 1.5 x ULN;
* aPTT, PT not to exceed 1.2 x ULN;
* Females must be surgically sterile, postmenopausal, have negative pregnancy test at screening;
* Females not surgically sterile or postmenopausal \& non-vasectomized males must practice at least one of the following methods of birth control:

  * Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to starting study drug);
  * Vasectomized partner;
  * Hormonal contraceptives for at least 3 months prior to study;
  * Double-barrier method (including condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).

Exclusion Criteria:

* History of/clinically suspicious for cancer-related CNS disease; An allogeneic stem cell transplant.
* Underlying, predisposing condition of bleeding/currently exhibits signs of bleeding.
* History of non-chemotherapy induced thrombocytopenic associated bleeding w/i 1 year prior to the 1st dose.
* Peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
* Active ITP/ history of being refractory to platelet transfusions.
* Significant history of cardiac, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic/hepatic disease.
* Females pregnant or breast-feeding.
* History of or active medical condition(s) that affects absorption or motility.
* Positive for HIV.
* Other clinically significant uncontrolled condition(s) including, but not limited to: active systemic fungal infection; neutropenic fever w/i 1 wk prior to study drug.
* Steroid therapy w/i 7 days prior to 1st dose for anti-cancer intent.
* Anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (except hormones for hypothyroidism or ERT)/agonists required to suppress serum testosterone levels \[e.g. LHRH, GnRH\], any investigational therapy w/i 14 days prior to first dose of study drug.
* Biologic agent w/i 30 days prior to 1st dose.
* Anticoagulation therapy/drugs/herbal supplements affecting platelet function.
* Aspirin w/i 7 days prior to 1st dose.
* Grapefruit/grapefruit products.

Primary outcomes:
measure: Assess the oral bioavailability of a new ABT-263 formulation relative to that of the current ABT-263 formulation being assessed in ongoing Phase 1/2a studies.
timeFrame: Two Period crossover design.
measure: Assess the oral bioavailability of a new ABT-263 formulation relative to that of the current ABT-263 formulation being assessed in ongoing Phase 1/2a studies and assess new ABT-263 formulations after once daily dosing (QD) and twice daily dosing (BID).
timeFrame: Three Period crossover design.
Secondary outcomes:
measure: Safety measures include number and percentage of subjects having treatment-emergent adverse events tabulated by MedDRA system organ class and preferred term, laboratory test results, lymphocyte enumeration results, vital signs, etc.
timeFrame: Two and three period crossover design
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: Site Reference ID/Investigator# 10281
state: California
city: Santa Monica
country: United States
facility: Site Reference ID/Investigator# 10282
state: California
city: Bethesda
country: United States
facility: Site Reference ID/Investigator# 16341
state: Maryland
city: Lebanon
country: United States
facility: Site Reference ID/Investigator# 9441
state: New Hampshire
city: Hackensack
country: United States
facility: Site Reference ID/Investigator# 20041
state: New Jersey
Study officials:
References: