Clinical trial NCT01686555: A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ABT-199 in Female Patients With Systemic Lupus Erythematosus (SLE)
Official title: Assessment of the Safety, Tolerability, and Pharmacokinetics of ABT-199 After Single and Multiple Ascending Doses in Female Subjects With Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lupus Erythematosus
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-09-18
Enrollment: 97
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Adverse Events
timeFrame: 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
measure: Physical Exam including vital signs
timeFrame: 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
measure: Clinical Lab Testing
timeFrame: 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
measure: Electrocardiogram (ECG) Measurements
timeFrame: 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
measure: Maximum observed serum concentration (Cmax) of ABT-199
timeFrame: For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199
measure: Time to Cmax (Tmax) of ABT-199
timeFrame: For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199
measure: The area under the time curve (AUC) of ABT-199
timeFrame: For 72 hours after a single dose of ABT-199 and for 24 hours after the seventh dose of multiple doses of ABT-199
measure: The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-199
timeFrame: For 72 hours after a single dose of ABT-199
Secondary outcomes:
measure: Measurement of lymphocyte depletion and recovery
timeFrame: 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
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Site Reference ID/Investigator# 89694
state: Florida
city: DeBary
country: United States
facility: Site Reference ID/Investigator# 131720
state: Florida
city: Miami Lakes
country: United States
facility: Site Reference ID/Investigator# 124116
state: Florida
city: Miami
country: United States
facility: Site Reference ID/Investigator# 118637
state: Florida
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 89693
state: Florida
city: Overland Park
country: United States
facility: Site Reference ID/Investigator# 78256
state: Kansas
city: Rochester
country: United States
facility: Site Reference ID/Investigator# 129826
state: Minnesota
city: Manhasset
country: United States
facility: Site Reference ID/Investigator# 89773
state: New York
city: Duncansville
country: United States
facility: Site Reference ID/Investigator# 78254
state: Pennsylvania
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 123335
state: Texas
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 78253
state: Texas
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 107896
city: Distrito Federal
country: Mexico
facility: Site Reference ID/Investigator# 116395
city: Monterrey
country: Mexico
facility: Site Reference ID/Investigator# 112555
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 132009
Study officials:
affiliation: AbbVie
name: Peng Lu, MD
role: STUDY_DIRECTOR
References:
citation: Lu P, Fleischmann R, Curtis C, Ignatenko S, Clarke SH, Desai M, Wong SL, Grebe KM, Black K, Zeng J, Stolzenbach J, Medema JK. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus. Lupus. 2018 Feb;27(2):290-302. doi: 10.1177/0961203317719334. Epub 2017 Jul 10.
citation: Nader A, Minocha M, Othman AA. Exposure-Response Analyses of the Effects of Venetoclax, a Selective BCL-2 Inhibitor, on B-Lymphocyte and Total Lymphocyte Counts in Women with Systemic Lupus Erythematosus. Clin Pharmacokinet. 2020 Mar;59(3):335-347. doi: 10.1007/s40262-019-00818-5.
citation: Minocha M, Zeng J, Medema JK, Othman AA. Pharmacokinetics of the B-Cell Lymphoma 2 (Bcl-2) Inhibitor Venetoclax in Female Subjects with Systemic Lupus Erythematosus. Clin Pharmacokinet. 2018 Sep;57(9):1185-1198. doi: 10.1007/s40262-017-0625-2.