Venetoclax for Healthy Subjects

No longer recruiting at 1 trial location

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: AbbVie

Disqualifiers: Renal, Neurologic, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a new formulation of the drug venetoclax is absorbed in the body under various conditions, including after a high-fat meal. Researchers are testing venetoclax in healthy female volunteers to determine if this new version is better absorbed than the existing one. Eligible participants must be healthy women who are postmenopausal, surgically sterile, or using birth control. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to early-stage drug development.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that venetoclax has undergone safety testing in several clinical trials. In one study with 158 participants, researchers found the drug to be safe at recommended doses.

The FDA has already approved venetoclax for certain conditions, indicating its safety for humans. However, some individuals have experienced side effects that led to discontinuing treatment. Other studies have reported common side effects, such as a drop in white blood cells, fever with low white blood cells, and pneumonia.

This trial focuses on healthy volunteers and a new version of the drug. While previous findings suggest venetoclax is generally safe, side effects can vary. This trial aims to better understand the safety of venetoclax in this specific context. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about venetoclax because it represents a promising approach in the treatment of certain blood cancers like chronic lymphocytic leukemia (CLL). Unlike traditional chemotherapy, which indiscriminately targets rapidly dividing cells, venetoclax specifically inhibits a protein called BCL-2. This protein helps cancer cells survive, so blocking it can lead to cancer cell death while sparing more healthy cells. Additionally, the study is exploring innovative formulations like hot melt extrusion, which could improve how the drug is absorbed in the body, potentially enhancing effectiveness and convenience for patients.

What evidence suggests that this trial's treatments could be effective?

Research has shown that venetoclax effectively treats some blood cancers by targeting a protein called BCL-2, which helps cancer cells survive. In earlier studies, patients taking venetoclax experienced a significant decrease in cancer cells. Testing has confirmed the drug's safety at recommended doses. While this trial explores different regimens of venetoclax, including a new tablet form, the drug has already proven effective in other forms. ^{2 3 4 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for healthy adult women. Participants must not have any significant health issues, be non-smokers or willing to abstain from smoking, and cannot be pregnant. They should not have taken any other medications recently that could affect the study results.

Inclusion Criteria

Body mass index (BMI) is 18.0 to 32.0 kg/m^2

I am either postmenopausal, surgically sterile, or using birth control if premenopausal.

Have CD19+ B-cell count > 150 cells/μL at screening

Exclusion Criteria

History of any clinically significant sensitivity or allergy to any medication or food

History of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, pulmonary, or hepatic diseases within the past 6 months that in the opinion of the investigator would adversely affect participation in this study

I have a condition or had surgery that could affect my stomach or intestine's function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various regimens of venetoclax under high-fat and fasting conditions to assess bioavailability and food effects

Approximately 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax

Trial Overview The study tests a new tablet form of Venetoclax, a medication typically used in certain blood cancers. It compares how the body absorbs this new version with food versus the standard one without food in healthy female volunteers.

How Is the Trial Designed?

Group I: Stage 2: Sequence 3: Venetoclax Experimental Treatment 1 Intervention

Participants will receive Regimen C, followed by Regimen A, finally followed by Regimen B, as part of the approximately 18 month study duration.

Group II: Stage 2: Sequence 2: Venetoclax Experimental Treatment 1 Intervention

Participants will receive Regimen B, followed by Regimen C, finally followed by Regimen A, as part of the approximately 18 month study duration.

Group III: Stage 2: Sequence 1: Venetoclax Experimental Treatment 1 Intervention

Participants will receive Regimen A, followed by Regimen B, finally followed by Regimen C, as part of the approximately 18 month study duration.

Group IV: Stage 1: Sequence 3: Venetoclax Experimental Treatment 1 Intervention

Participants will receive Regimen C, followed by Regimen A, followed by Regimen B, finally followed by Regimen D, as part of the approximately 18 month study duration.

Group V: Stage 1: Sequence 2: Venetoclax Experimental Treatment 1 Intervention

Participants will receive Regimen B, followed by Regimen C, followed by Regimen A, finally followed by Regimen D, as part of the approximately 18 month study duration.

Group VI: Stage 1: Sequence 1: Venetoclax Experimental Treatment 1 Intervention

Participants will receive commercial venetoclax following a high-fat meal (Regimen A), followed by venetoclax hot melt extrusion-03 (HME-03) dose A following a high-fat meal (Regimen B), followed by venetoclax HME-03 dose B following a high-fat meal (Regimen C), finally followed by venetoclax HME-03 dose A following fasting (Regimen D), as part of the approximately 18 month study duration.

Venetoclax is already approved in United States, European Union for the following indications:

Approved in United States as Venclexta for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Approved in European Union as Venclyxto for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

The H-1337 ophthalmic solution demonstrated significant reductions in intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension, with mean changes of -4.45, -5.16, and -4.93 mmHg for the different concentrations compared to a vehicle control, indicating its efficacy as a treatment.

While 49% of subjects experienced treatment-emergent adverse events, most were mild, suggesting that H-1337 is generally well tolerated, with only a small number of moderate intensity side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ⅰ/Ⅱ, Double-Masked, Randomized, Vehicle-Controlled Study of H-1337 Ophthalmic Solution for Glaucoma and Ocular Hypertension. Hartman, PJ., Cooke, DL., Hsu, HH., et al.[2023]

In a randomized double-blind study of 42 patients with primary open-angle glaucoma (POAG), Naftidrofuryl did not show significant efficacy compared to placebo across most measured parameters, including intraocular pressure and visual acuity.

The only notable finding was a decrease in CLV (a specific measure) at 12 weeks in the Naftidrofuryl group, suggesting that while it may have some effect, it is not as effective for POAG as it is for normal tension glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of naftidrofuryl (Praxilene) in primary open angle glaucoma: prospective double-blind study]. Beati, D., Mermoud, A., Faggioni, R.[2013]

In a 4-week trial involving 18 patients with retinal vein thrombosis, pentoxifylline (PXF) at 1600 mg daily significantly improved retinal flow compared to placebo, with a 350% increase in retinal vein flow velocity (RVFV) versus 200% in the placebo group.

No side effects were reported, and PXF also led to a greater reduction in visual analogue scores, indicating better clinical outcomes, making it a promising treatment option for retinal vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of retinal vein thrombosis with pentoxifylline: a controlled, randomized trial. De Sanctis, MT., Cesarone, MR., Belcaro, G., et al.[2013]

In a study of 485 claudicant patients, those with a maximal walking distance of 250 meters or less showed significant improvement in walking capacity when treated with propionyl-L-carnitine compared to placebo, with a 98% increase in walking distance for the treatment group.

Patients with mild functional impairment (walking distance greater than 250 meters) did not benefit from propionyl-L-carnitine, indicating that the treatment is most effective for those with more severe walking limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European multicenter study on propionyl-L-carnitine in intermittent claudication. Brevetti, G., Diehm, C., Lambert, D.[2019]

In a meta-analysis of 28 studies involving 386 patients, bimatoprost and travoprost were found to be the most effective ocular hypotensive medications, achieving a 29% and 27% reduction in intraocular pressure (IOP) over 24 hours, respectively.

The study also revealed that evening dosing of latanoprost resulted in a greater IOP reduction (24%) compared to morning dosing (18%), highlighting the importance of dosing time in managing glaucoma effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of 24-hour intraocular pressure studies evaluating the efficacy of glaucoma medicines. Stewart, WC., Konstas, AG., Nelson, LA., et al.[2022]

Citations

1. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000PharmR.pdf

208573Orig1s000 - accessdata.fda.gov Venetoclax has an acceptable safety pharmacology profile at doses achieving plasma concentrations relevant to the recommended human daily dose ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01328626

NCT01328626 | A Phase 1 Study Evaluating the Safety ... This is a Phase 1, open-label, multicenter study evaluating the safety and PK profile of ABT-199 under a once daily dosing schedule.

3. ashpublications.org ashpublications.org/blood/article/126/23/254/112989/A-Phase-1-Study-of-Venetoclax-ABT-199-GDC-0199

A Phase 1 Study of Venetoclax (ABT-199 / GDC-0199 ... ... safety, pharmacokinetics, and efficacy of venetoclax monotherapy. We present updated data on the safety profile and efficacy as of June 10, 2015 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11112299/

Clinical pharmacokinetics and pharmacodynamics of ... Venetoclax pharmacokinetics has been extensively characterized in patients and healthy participants. After oral dosing, the median time to reach maximum plasma ...

5. abbvie.com abbvie.com/content/dam/abbvie-dotcom/us/clinical-trials/venetoclax_M13-982.pdf

Venetoclax (ABT-199) M13-982 Clinical Study Report Safety was assessed in all 158 subjects; 107 subjects in the main cohort and 51 subjects in the safety expansion cohort. The data cutoff date for this final ...

6. venclextahcp.com venclextahcp.com/cll/side-effects/ven-g-safety-profile.html

VEN+G Safety Data for CLL/SLL - venclexta In the VEN+G arm, adverse reactions led to treatment discontinuation in 16% of patients, dose reduction in 21%, and dose interruption in 74% · Neutropenia led to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5026291/

The potential of venetoclax (ABT-199) in chronic lymphocytic ... Severe adverse events (SAEs) included TLS (3% including 1 death), febrile neutropenia (6%), and pneumonia (4%). Overall, eight patients discontinued therapy due ...