New Formulations of TEV-56286 for Healthy Subjects

Overseen By Teva U.S. Medical Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Teva Branded Pharmaceutical Products R&D LLC

Disqualifiers: Alcohol, Drug abuse, Arrhythmia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 25 days

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The primary objective of the study is to assess the relative bioavailability of TEV-56286 test formulations compared to TEV-56286 reference product in healthy adult participants. The secondary objective is to evaluate the safety and tolerability of TEV-56286. The planned duration for each participant is approximately 70 days which includes a 45 day screening period.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please contact the investigator for more details.

What safety data exists for TEV-56286 or similar treatments in humans?

Tezosentan, a treatment similar to TEV-56286, has been studied for safety in both patients with heart failure and healthy subjects. It was generally well tolerated, with no significant safety concerns noted during prolonged infusions in patients or chronic infusions in healthy subjects. ^{1 2 3 4 5}

How is the drug TEV-56286 different from other treatments for HIV?

TEV-56286, a new formulation of tenofovir, is unique because it uses a stability-enhanced solid-state crystal form that improves its solubility and stability, potentially offering better bioavailability compared to existing tenofovir formulations. ^{6 7 8 9 10}

Who Is on the Research Team?

Teva Medical Expert, MD

Principal Investigator

Teva Branded Pharmaceutical Products R&D LLC

Are You a Good Fit for This Trial?

This trial is for healthy adults with a BMI of 18.5 to 32 who agree to prevent pregnancy during the study. Men must use contraception unless they are sterile. People can't join if they have a history of heart issues, are in another trial, have substance abuse within the last year, donated blood recently or plan surgery.

Inclusion Criteria

Body mass index (BMI) between 18.5 kg/m2 to 32.0 kg/m2 (inclusive)

I agree to use birth control during the study.

I am a male willing to use contraception if I'm not sterile.

Exclusion Criteria

I or my family have a history of heart rhythm problems or sudden deaths before 40.

Participation in another clinical trial simultaneously

History of alcohol, drug or any other substance, abuse, addiction or dependence in the last 12 months (except for caffeine)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

45 days

Treatment

Participants receive single-dose administration of TEV-56286 test and reference formulations in a randomized crossover design

Approximately 25 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TEV-56286

Trial Overview The study tests how the body absorbs two versions of TEV-56286: one already known (reference) and one new (test). It checks which formulation enters the bloodstream better over approximately 70 days including screening and follow-up.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Random sequence of test and reference formulations

Group II: Cohort 1 Experimental Treatment 2 Interventions

Random sequence of test and reference formulations

Who Is Running the Clinical Trial?

Teva Branded Pharmaceutical Products R&D LLC

Lead Sponsor

Published Research Related to This Trial

A systematic review of 21 trials involving 3,644 patients found that endothelin receptor antagonists, particularly bosentan, significantly increase the risk of hepatotoxicity, with a relative risk of 2.92 for any hepatic adverse reaction.

When hepatotoxicity was specifically defined as liver enzyme elevations three times above normal, the relative risk rose to 2.98, indicating a concerning safety profile for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hepatotoxicity in patients treated with endothelin receptor antagonists: systematic review and meta-analysis of randomized clinical trials]. Macías Saint-Gerons, D., de la Fuente Honrubia, C., Montero Corominas, D., et al.[2018]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

[Hepatotoxicity in patients treated with endothelin receptor antagonists: systematic review and meta-analysis of randomized clinical trials]. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of the ETA-selective endothelin receptor antagonist SPP301 in healthy human subjects. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

A pilot safety trial of prolonged (48 h) infusion of the dual endothelin-receptor antagonist tezosentan in patients with advanced heart failure. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Feasibility of Stability-Enhanced Solid-State (SESS) Tenofovir Disoproxil Free Base Crystal. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

An Open-Label Pharmacokinetic and Pharmacodynamic Assessment of Tenofovir Gel and Oral Emtricitabine/Tenofovir Disoproxil Fumarate. [2023]

8. England pubmed.ncbi.nlm.nih.gov

HIV treatment simplification to elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) plus darunavir: a pharmacokinetic study. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066). [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Development of rectal enema as microbicide (DREAM): Preclinical progressive selection of a tenofovir prodrug enema. [2021]