Osivelotor for Liver Disease

Recruiting at 3 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Disqualifiers: Hepatic carcinoma, Hepatorenal syndrome, others

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

Compensation: Varies

Number of Visits: 10

Duration: 5 days

8 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should have stable concomitant medications for managing their medical history, which suggests you may continue your current medications if they are stable.

What data supports the idea that the drug Osivelotor for Liver Disease is an effective treatment?

The available research does not provide specific data on Osivelotor for Liver Disease. Instead, it discusses other treatments like cilofexor and vonafexor for liver conditions such as nonalcoholic steatohepatitis (NASH). Cilofexor was shown to be generally well tolerated and increased certain beneficial factors in the body, while vonafexor was studied for its safety and effectiveness in improving liver conditions. Without specific data on Osivelotor, we can't conclude its effectiveness for liver disease based on the provided information. ^{1 2 3 4 5}

What safety data is available for Osivelotor in treating liver disease?

The provided research does not contain specific safety data for Osivelotor (also known as GBT-021601, GBT-601, PF-07940367) in the treatment of liver disease. The studies mentioned focus on other compounds and their safety profiles, such as ZSP1601 and BMS-986339, but do not address Osivelotor directly. ^{2 6 7 8 9}

Is the drug Osivelotor a promising treatment for liver disease?

The provided research articles do not mention Osivelotor or its potential as a treatment for liver disease, so we cannot determine if it is promising based on this information. ^{3 10 11 12 13}

What is the purpose of this trial?

The purpose of this study is to understand how Osivelotor is processed in people with loss of liver function. This study is seeking participants that are: * stable loss of liver function with mild or moderate severity * none of underlying conditions possibly affecting the study medicine being absorbed by the body All participants will receive one amount of Osivelotor by mouth before breakfast on the first day at the study clinic. A number of blood samples will be collected to understand how Osivelotor is changed and removed from the body. Participants will also have to undergo physical examination and other tests. This will help to understand if Osivelotor is safe. Participants will take part in the study for a maximum of 112 days. During this time, participants will have to stay onsite for 5 days. There will be 5 study visits at the study clinic.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This study is for individuals with stable liver disease of mild or moderate severity, who have a BMI between 16 to 40 kg/m2 and weigh over 50 kg. They should not have had significant changes in their condition within the last month and must be on stable medications for any other health issues.

Inclusion Criteria

My current medications for other conditions are stable.

Body mass index (BMI) of 16 to 40 kg/m2, inclusive; and a total body weight greater than 50 kg (greater than 110 lb)

My liver function is stable, fitting into Class A or B.

Exclusion Criteria

I have had surgery that could affect how my body absorbs medication.

I have liver problems confirmed by tests or a doctor's exam.

I have liver cancer, kidney issues related to liver disease, or a short expected lifespan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Osivelotor orally under fasted conditions, followed by blood sampling and physical examinations

5 days

5 days onsite

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

5 study visits at the clinic

Treatment Details

Interventions

• Osivelotor

Trial Overview The trial is testing how Osivelotor, a medication taken by mouth, is processed by people with impaired liver function. Participants will take one dose before breakfast on the first day and undergo blood tests, physical exams, and other assessments over a maximum of 112 days with five clinic visits.

Participant Groups

Group I: Group 2 Experimental Treatment 1 Intervention

Participants with mild hepatic impairment will receive a single dose of osivelotor, administered orally under fasted conditions.

Group II: Group 1 Experimental Treatment 1 Intervention

Participants with moderate hepatic impairment will receive a single dose of osivelotor, administered orally under fasted conditions.

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Cilofexor, a nonsteroidal FXR agonist, was well tolerated in a study of 120 healthy participants, with mild to moderate treatment-emergent adverse events, primarily headaches, indicating a favorable safety profile for further testing.

The drug effectively increased levels of FGF19 and reduced bile acids in a dose-dependent manner, suggesting its potential efficacy in treating conditions like NASH and PSC, with optimal FXR activation observed at doses above 30 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal Farnesoid X receptor agonist, in healthy volunteers. Younis, IR., Kirby, BJ., Billin, AN., et al.[2023]

In a phase 2 trial involving 140 patients with nonalcoholic steatohepatitis (NASH), cilofexor 100 mg daily for 24 weeks significantly reduced liver fat content by 22.7% compared to a placebo, indicating its efficacy in treating hepatic steatosis.

Cilofexor was generally well-tolerated, although moderate to severe itching was reported more frequently in the 100 mg group (14%) compared to the lower dose and placebo, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Patel, K., Harrison, SA., Elkhashab, M., et al.[2021]

In the LIVIFY trial involving 120 patients with suspected fibrotic NASH, vonafexor significantly reduced liver fat content after 12 weeks, with the 100 mg and 200 mg doses showing reductions of -6.3% and -5.4% respectively, compared to -2.3% in the placebo group.

Vonafexor was found to be safe, leading to improvements in liver enzymes, body weight, and even renal function, although mild to moderate pruritus was reported in some patients, indicating manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. Ratziu, V., Harrison, SA., Loustaud-Ratti, V., et al.[2023]

Robuvit® supplementation for 3 months in patients with non-alcoholic fatty liver disease (NAFLD) significantly improved liver function markers, including decreased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating better hepatic metabolism.

The study, involving 34 subjects, showed that Robuvit® was well-tolerated with no side effects, and it also led to a significant reduction in liver size and echogenicity, suggesting a prevention of progression to liver fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Robuvit® on the progression of non-alcoholic fatty liver disease. Belcaro, G., Cox, DM., Cesarone, MR., et al.[2022]

The NATIVE study is a Phase 2b clinical trial assessing the safety and efficacy of lanifibranor, a panPPAR agonist, in treating non-cirrhotic non-alcoholic steatohepatitis (NASH) over 24 weeks, involving adult patients with specific histological criteria.

The primary goal is to achieve a 2-point reduction in the SAF histological score, indicating improved liver inflammation and ballooning without worsening fibrosis, highlighting lanifibranor's potential to address multiple aspects of NASH pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, placebo-controlled, multi-centre, dose-range, proof-of-concept, 24-week treatment study of lanifibranor in adult subjects with non-alcoholic steatohepatitis: Design of the NATIVE study. Sven M, F., Pierre, B., Manal F, A., et al.[2021]

A new class of hybrid molecules has been developed that acts as both antagonists of the cysteinyl leukotriene receptor 1 (CysLT1R) and agonists of the G protein bile acid receptor 1 (GPBAR1/TGR5), showing potential for treating nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

In preclinical models, the most effective compound demonstrated the ability to reverse liver damage and improve lipid and energy metabolism, indicating its efficacy in addressing the underlying issues of NAFLD/NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of a Potent and Orally Active Dual GPBAR1/CysLT1R Modulator for the Treatment of Metabolic Fatty Liver Disease. Fiorucci, S., Rapacciuolo, P., Fiorillo, B., et al.[2022]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

In a trial involving 36 patients with non-alcoholic fatty liver disease (NAFLD), the pan-phosphodiesterase inhibitor ZSP1601 was found to be well-tolerated, with 75% of participants experiencing mild to moderate treatment-emergent adverse events, but no serious adverse events reported.

ZSP1601 demonstrated effective improvements in liver chemistries, liver fat content, and fibrosis, suggesting it could be a promising treatment option for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial. Hu, Y., Li, H., Zhang, H., et al.[2023]

Compound 32 (BMS-986339) is a novel FXR agonist that shows potent activation of the farnesoid X receptor, with tissue-selective effects that may lead to fewer side effects compared to other FXR agonists.

In preclinical studies, Compound 32 demonstrated strong antifibrotic efficacy in treating nonalcoholic steatohepatitis (NASH) while potentially reducing adverse effects like pruritus and elevated plasma lipids, suggesting it could be a safer alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis. Nara, SJ., Jogi, S., Cheruku, S., et al.[2022]

In a study involving 16 participants (8 with moderate hepatic insufficiency and 8 healthy controls), the pharmacokinetics of a single 40-mg dose of laropiprant (LRPT) showed that patients with hepatic insufficiency had significantly higher exposure to the drug, with an estimated geometric mean ratio (GMR) of 2.78 for the area under the curve (AUC).

Despite the increased exposure, the single-dose LRPT was generally well tolerated in all participants, indicating that while hepatic insufficiency affects drug levels, it does not necessarily lead to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, in patients with moderate hepatic impairment. Wang, YH., Liu, F., Luk, JA., et al.[2018]

In a phase 3 trial involving 363 Japanese patients with hepatitis C virus genotype 1b, a 12-week treatment regimen of coformulated ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) achieved a high sustained virological response rate of 94.6% in patients without cirrhosis.

The treatment demonstrated a favorable safety profile, with a low discontinuation rate due to adverse events (0%-2.4%) and the most common side effect being nasopharyngitis, indicating that OBV/PTV/r is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Kumada, H., Chayama, K., Rodrigues, L., et al.[2022]

In a real-world study involving 58 patients with hepatitis C virus genotype 1, a 12-week treatment with paritaprevir, ombitasvir, and ritonavir achieved a high sustained virological response (SVR) rate of 96.6%, demonstrating its efficacy even in patients with prior treatment failures.

The treatment was found to be safe, with only 26% of patients experiencing mild adverse events and no severe adverse events reported, indicating a favorable safety profile for patients with chronic hepatitis or compensated hepatic cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Real-world Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir for Hepatitis C Genotype 1. Miyasaka, A., Yoshida, Y., Yoshida, T., et al.[2021]

The multicentric observational study compared the effects of obeticholic acid and fibrates in patients with primary biliary cholangitis, highlighting their efficacy in managing this liver disease.

Results indicated that obeticholic acid may provide superior benefits in improving liver function tests compared to fibrates, suggesting it could be a more effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing Medical Education Questions: November 2021. Richter, SJ.[2023]

References

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

Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal Farnesoid X receptor agonist, in healthy volunteers. [2023]

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

Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Effects of Robuvit® on the progression of non-alcoholic fatty liver disease. [2022]

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

A randomised, double-blind, placebo-controlled, multi-centre, dose-range, proof-of-concept, 24-week treatment study of lanifibranor in adult subjects with non-alcoholic steatohepatitis: Design of the NATIVE study. [2021]

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

Discovery of a Potent and Orally Active Dual GPBAR1/CysLT1R Modulator for the Treatment of Metabolic Fatty Liver Disease. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]

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

ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial. [2023]

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

Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, in patients with moderate hepatic impairment. [2018]

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

Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

The Real-world Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir for Hepatitis C Genotype 1. [2021]

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

Continuing Medical Education Questions: November 2021. [2023]