Study to Assess Adverse Events and the Movement of Oral Venetoclax Tablet Through the Body of Female Participants Aged 18-75 Years With Impaired Renal Function

Sponsor

AbbVie (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04810598

Collaborator

Roche-Genentech (Industry)

Enrollment

Locations

Arms

12.7

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Renal insufficiency is common in participants with blood cancers. The main objective of this study is to evaluate adverse events and movement of oral venetoclax tablets through the body of female participants with severe normal renal function and those with end stage renal disease (ESRD) requiring hemodialysis.

Venetoclax is an investigational drug being developed for the treatment of various hematologic malignancies. Study doctors put the participants in 1 of 2 groups, called treatment arms. Each group receives a different treatment. Approximately 12 female participants between 18 and 75 years, with Body Mass Index (BMI) between 18 to 42 kg/m2 will be enrolled in approximately 4 sites across the world.

Participants with normal renal function will receive single dose of oral venetoclax tablet. Participants with ESRD will receive oral venetoclax tablets just prior to hemodialysis (Period 1 Day 1) and between dialysis days (Period 2 Day 1), doses in the two periods will be separated by at least 7 days.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood and urine tests, checking for side effects.

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment Renal Disease	Drug: Venetoclax	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Evaluation of the Pharmacokinetics and Safety of Venetoclax in Subjects With Impaired Renal Function

Actual Study Start Date :

Jul 8, 2021

Anticipated Primary Completion Date :

Jul 29, 2022

Anticipated Study Completion Date :

Jul 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Participants With Normal Renal Function Participants with normal renal function will receive single dose of venetoclax on Day 1.	Drug: Venetoclax Oral Tablet Other Names: Venclexta ABT-199 GDC-0199
Experimental: Group 2: Participants With End Stage Renal Disease Participants with end stage renal disease (ESRD) will receive single dose of venetoclax on Period 1 Day 1 and Period 2 Day 1 (Each period is 3 days separated by 7-day washout period).	Drug: Venetoclax Oral Tablet Other Names: Venclexta ABT-199 GDC-0199

Arm

Intervention/Treatment

Experimental: Group 1: Participants With Normal Renal Function

Participants with normal renal function will receive single dose of venetoclax on Day 1.

Drug: Venetoclax

Oral Tablet

Other Names:

Venclexta

ABT-199

GDC-0199

Experimental: Group 2: Participants With End Stage Renal Disease

Participants with end stage renal disease (ESRD) will receive single dose of venetoclax on Period 1 Day 1 and Period 2 Day 1 (Each period is 3 days separated by 7-day washout period).

Drug: Venetoclax

Oral Tablet

Other Names:

Venclexta

ABT-199

GDC-0199

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Adverse Events (AEs) [Up to approximately 38 days]
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Maximum Plasma Concentration (Cmax) of Venetoclax (Groups 1,2) [Up to Day 6]
Maximum Plasma Concentration (Cmax) of Venetoclax.
Time to Cmax (Tmax) of Venetoclax (Groups 1,2) [Up to Day 6]
Time to Cmax (Tmax) of Venetoclax.
Area Under the Plasma Concentration-time Curve over time from time 0 to 48 hours (AUC0-48) of Venetoclax (Groups 1,2) [Up to Day 6]
Area Under the Plasma Concentration-time Curve over time from time 0 to 48 hours (AUC0-48).
Pre-dose Unbound Fraction (fu) of Venetoclax in Plasma (Groups 1,2) [Day 1]
Unbound Fraction (fu) of Venetoclax in Plasma.
Dialysis Clearance (CLdialysis) (Group 2) [Day 1]
Dialysis Clearance (CLdialysis) is calculated in participants undergoing hemodialysis in Period 1.
Unbound Fraction Pre-dialysis (fu,predialysis) of Venetoclax in Plasma (Group 2) [Day 1]
Unbound fraction pre-dialysis (fu,predialysis) of venetoclax in plasma is calculated in participants undergoing hemodialysis in Period 1.
Unbound Fraction Post-dialysis (fu,postdialysis) of Venetoclax in Plasma (Group 2) [Day 1]
Unbound fraction post-dialysis (fu,postdialysis) of venetoclax in plasma is calculated in participants undergoing hemodialysis in Period 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Body mass index (BMI) between 18.0 and 42.0 kg/m2.
Postmenopausal or permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
Women of childbearing potential, practicing at least 2 protocol specified methods of birth control that are effective from at least 30 days before starting study drug through at least 30 days after the last dose of any study drug.
Group 1 only: Must be in general good health based upon the results of a medical history, physical examination, and 12-lead electrocardiogram (ECG) with normal Glomerular Filtration Rate (GFR) at Screening.
Group 2 only: Stable condition and acceptable for study participation based upon the results of a medical history, physical examination, laboratory profile, and ECG. Participant with end stage renal disease (ESRD) requiring dialysis on hemodialysis must have been receiving hemodialysis for at least 1 month.