A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ABT-199 in Female Patients With Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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To assess the safety, tolerability and pharmacokinetics of ABT-199 in female subjects with Systemic Lupus Erythematosus.

Detailed Description
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This is a phase 1, randomized, double-blind, placebo-controlled, single-and multiple ascending dose study. Up to eighty-eight subjects with Systemic Lupus Erythematosus will be selected to participate. Subjects will be randomized to receive either ABT-199 or placebo. Subjects will be administered ABT-199/placebo as a single dose or up to 14 days as multiple doses.

Official Title
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Assessment of the Safety, Tolerability, and Pharmacokinetics of ABT-199 After Single and Multiple Ascending Doses in Female Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Lupus Erythematosus

Intervention / Treatment
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* Drug: ABT-199
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of systemic lupus erythematosus for at least 6 months. Documentation of at least one of the following: ANA titer >= 1:160 or positive anti-dsDNA antibodies. Stable systemic lupus erythematosus medication regimen. Other than systemic lupus erythematosus, subject should be in general good health. Exclusion Criteria: Male. Drug-induced or highly active systemic lupus erythematosus. Significant autoimmune disease other than lupus. Significant, uncontrolled or unstable disease in any organ.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Dose<br>Subjects enrolled in the Single Ascending Dose (SAD) part of the study will receive a single dose of study drug or placebo. (Groups 1, 2, 3, 4, 5 and 6). | Drug: ABT-199<br>* Tablet<br>Other: Placebo<br>* Tablet<br>|
| Experimental: Multiple Dose<br>Subjects enrolled in the Multiple Ascending Dose (MAD) part of the study will receive multiple doses of study drug or placebo. (Groups 7, 8, 9, 10 and 11) | Drug: ABT-199<br>* Tablet<br>Other: Placebo<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events | Collect all adverse events at each visit | From first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199 | 
| Physical Exam including vital signs | Blood pressure, heart rate and body temperature | Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199 | 
| Clinical Lab Testing | Hematology, Chemistry, and Urinalysis | Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199 | 
| Electrocardiogram (ECG) Measurements | ECGs done in triplicate | For 24 hours after a single dose of ABT-199 and up to 24 hours after the seventh dose of multiple doses of ABT-199 | 
| Maximum observed serum concentration (Cmax) of ABT-199 | Cmax | For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199 | 
| Time to Cmax (Tmax) of ABT-199 | Time to Cmax | For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199 | 
| The area under the time curve (AUC) of ABT-199 | the area under the exposure-time curve of ABT-199 extrapolated to infinite time for single doses and up to 24 hrs for multiple doses of ABT-199 | For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199 | 
| The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199 | The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199 | For 72 hours after a single dose of ABT-199 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of lymphocyte depletion and recovery | explore pharmacokinetic/pharmacodynamic relationship | Prior to the first dose of ABT-199 until 28 days after single dose of ABT-199 and until 21 days after the last multiple dose of ABT-199 |