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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Renal Disease
• Intervention / Treatment: Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Ctr /ID# 224922
  • Illinois
    • Grayslake, Illinois, United States, 60030
      • Acpru /Id# 243398

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Exclusion Criteria:

- Participants on a strict vegetarian or vegan diet.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	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.	Up to approximately 38 days
Maximum Plasma Concentration (Cmax) of Venetoclax (Groups 1,2)	Maximum Plasma Concentration (Cmax) of Venetoclax.	Up to Day 6
Time to Cmax (Tmax) of Venetoclax (Groups 1,2)	Time to Cmax (Tmax) of Venetoclax.	Up to Day 6
Area Under the Plasma Concentration-time Curve over time from time 0 to 48 hours (AUC0-48) of Venetoclax (Groups 1,2)	Area Under the Plasma Concentration-time Curve over time from time 0 to 48 hours (AUC0-48).	Up to Day 6
Pre-dose Unbound Fraction (fu) of Venetoclax in Plasma (Groups 1,2)	Unbound Fraction (fu) of Venetoclax in Plasma.	Day 1
Dialysis Clearance (CLdialysis) (Group 2)	Dialysis Clearance (CLdialysis) is calculated in participants undergoing hemodialysis in Period 1.	Day 1
Unbound Fraction Pre-dialysis (fu,predialysis) of Venetoclax in Plasma (Group 2)	Unbound fraction pre-dialysis (fu,predialysis) of venetoclax in plasma is calculated in participants undergoing hemodialysis in Period 1.	Day 1
Unbound Fraction Post-dialysis (fu,postdialysis) of Venetoclax in Plasma (Group 2)	Unbound fraction post-dialysis (fu,postdialysis) of venetoclax in plasma is calculated in participants undergoing hemodialysis in Period 1.	Day 1

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Roche-Genentech

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2021
• Primary Completion (Actual): August 16, 2022
• Study Completion (Actual): August 16, 2022

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Renal Impairment; Venetoclax; Venclexta; Renal Disease; End stage renal disease (ESRD)
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: M19-065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes