Assess the Oral Bioavailability of a New ABT-263 Formulation in Healthy Female Subjects

Study Overview
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Brief Summary
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This is a Phase 1, randomized, open-label, single center, three period crossover study to determine the oral bioavailability of a new ABT-263 formulation relative to that of the current ABT-263 formulation being administered in ongoing Phase 1/2a studies. Approximately 12 healthy female subjects will be enrolled in this study.

Detailed Description
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This is a Phase 1, randomized, open-label, single center, three period crossover study to determine the oral bioavailability of a new ABT-263 formulation relative to that of the current ABT-263 formulation being administered in ongoing Phase 1/2a studies. Approximately 12 healthy female subjects will be enrolled in this study.

Conditions
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Healthy Female Subjects

Intervention / Treatment
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* Drug: ABT-263
* Drug: ABT-263
* Drug: ABT-263


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and age is between 18 and 55 years, inclusive. Must be surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), postmenopausal (for at least 2 years), or practicing at least one acceptable method of birth control. Must have negative results for pregnancy tests performed at Screening on a urine sample obtained within 28 days prior to initial study drug administration, and on Period 1 Day -1 on a serum specimen. Body Mass Index (BMI) is 18 to 29, inclusive. BMI is calculated as weight in kg divided by the square of height measured in meters. Must have adequate bone marrow function per local laboratory reference range (Platelets >/= lower limit of normal range, ANC >/= lower limit of normal range) A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG). Must voluntarily sign and date each informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any study-specific procedures. Exclusion Criteria: History of significant sensitivity to any drug History of drug or alcohol abuse w/i 6 months or currently receiving Disulfiram Known/suspected history of HIV History of or active medical condition(s) or surgical procedure(s) that might affect GI motility, pH, absorption History of thrombocytopenic associated bleeding w/i 1 year prior to ABT-263 Significant history of cardiovascular disease (e.g., MI, thrombotic or thromboembolic event in last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, respiratory (except mild asthma), gastrointestinal, hematologic, or hepatic disease or diabetes, cancer, epilepsy, or seizures that in the opinion of the PI would adversely affect her participating in the study. Underlying condition predisposing to bleeding or currently exhibits signs of clinically significant bleeding or active peptic ulcer disease or other hemorrhagic esophagitis/gastritis. Positive result for drugs of abuse, alcohol, cotinine, hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab). Consumed alcohol, grapefruit or starfruit product, or Seville oranges w/i 3 days prior to ABT-263 Received aspirin, anticoagulation therapy, or any drugs or herbal supplements that affect platelet function w/i 7 days prior to/during ABT-263 Used any medications, vitamins, or herbal supplements (except contraceptives) w/i 14 days prior to ABT-263 Received any drug by injection or biologic agent w/i 30 days prior to ABT-263 (except parenteral hormonal contraceptives) Used known inhibitors or inducers CYP3A w/i 1 month prior to ABT-263; Received any investigational product w/i 6 weeks prior to ABT-263 Used tobacco or nicotine-products w/i 6 months prior to ABT-263 Pregnant or breastfeeding Donation or loss of >/=550 mL blood or received transfusion of blood product w/i 8 weeks prior ABT-263 Currently enrolled in another study. The PI decides the subject is unsuitable to receive ABT-263.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence I<br> | Drug: ABT-263<br>* Period 1: Single (oral) dose of 25 mg of Formulation A Period 2: Single (oral) dose of 25 mg of Formulation B1 Period 3: Single (oral) dose of 25 mg of Formulation B2<br>|
| Experimental: Sequence II<br> | Drug: ABT-263<br>* Period 1: Single (oral) dose of 25 mg of Formulation B1 Period 2: Single (oral) dose of 25 mg of Formulation B2 Period 3: Single (oral) dose of 25 mg of Formulation A<br>|
| Experimental: Sequence III<br> | Drug: ABT-263<br>* Period 1: Single (oral) dose of 25 mg of Formulation B2 Period 2: Single (oral) dose of 25 mg of Formulation A Period 3: Single (oral) dose of 25 mg of Formulation B1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the oral bioavailability of Formulation B1 and Formulation B2 via pharmacokinetic measurements relative to Formulation A . |  | Each formulation assessed via 13 PK timepoints over 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome measures include adverse event monitoring, vital signs, physical examinations, ECGs, and laboratory assessments including pharmacogenetics. |  | Assessed over the confinement period of 17 days of study duration |