Zasocitinib for Healthy Adults

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Takeda

Must not be taking: CYP3A4 inducers

Disqualifiers: Herpes, Viral diseases, Tuberculosis, others

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

Compensation: Varies

Number of Visits: 27

Duration: 27 days

78 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription or non-prescription medications, herbal remedies, or vitamin supplements before joining the trial. Additionally, you must avoid any drugs that affect certain liver enzymes (CYP3A4) for 28 days before the trial starts.

What data supports the effectiveness of the drug Zasocitinib for healthy adults?

The research on similar drugs like tofacitinib and upadacitinib, which are also Janus kinase inhibitors, shows they are effective in treating conditions like rheumatoid arthritis and ankylosing spondylitis. This suggests that Zasocitinib, being in the same class, might also be effective. ^{1 2 3 4 5}

Is Zasocitinib safe for humans?

Zasocitinib, also known as tofacitinib, has been studied for safety in various conditions like rheumatoid arthritis and ulcerative colitis. Some reported side effects include infections, blood clots, and gastrointestinal issues. It's important to discuss potential risks with a healthcare provider before participating in a trial. ^{2 6 7 8 9}

How is the drug Zasocitinib different from other treatments?

Zasocitinib is unique because it is a Janus kinase inhibitor, similar to Tofacitinib, which is used for conditions like ulcerative colitis and rheumatoid arthritis. This class of drugs works by blocking specific enzymes involved in inflammation, offering a different mechanism of action compared to traditional treatments. ^{2 10 11 12 13}

What is the purpose of this trial?

The main aim of this study is to find out how zasocitinib (TAK-279) interacts with other medicines taken by mouth (orally). This will be examined by how the body processes medicines, which is called pharmacokinetics or PK. In this study, other medicines that will be administered together with zasocitinib include a contraceptive (levonorgestrel (LNG) and ethinyl estradiol \[EE\]), a medicine for diabetes (metformin), a medicine used for heart problems (digoxin), and a medicine that blocks the production of stomach acid (esomeprazole). Another aim is to learn about the side effects of zasocitinib and how well it is tolerated when taken alone and together with these other medicines. During the study, participants will need to stay at the clinic for up to 27 days.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for healthy adults who can stay at the clinic for up to 27 days. It's not specified who can't join, but typically people with ongoing health issues or those taking conflicting medications would be excluded.

Inclusion Criteria

Body mass index (BMI) must be >= 18.0 and <= 32.0 kg/m^2 at the screening visit

I am between 18 and 55 years old and considered healthy.

I am generally healthy with no significant medical issues.

Exclusion Criteria

Positive urine drug or alcohol results at the screening visit or at check-in

I cannot stop taking my current medications, supplements, or herbal remedies.

Has herpes infections

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Zasocitinib in combination with other medications across four parts: COC, Metformin, Digoxin, and Esomeprazole

27 days

In-clinic stay for up to 27 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 days

Treatment Details

Interventions

• Zasocitinib

Trial Overview The study tests how Zasocitinib (TAK-279) interacts with other oral medicines: a contraceptive (levonorgestrel and ethinyl estradiol), Metformin for diabetes, Digoxin for heart conditions, and Esomeprazole that reduces stomach acid.

Participant Groups

Group I: Part 4: Zasocitinib + Esomeprazole Experimental Treatment 2 Interventions

Group II: Part 3: Digoxin + Zasocitinib Experimental Treatment 2 Interventions

Group III: Part 2: Metformin + Zasocitinib Experimental Treatment 2 Interventions

Group IV: Part 1: COC (LNG and EE) + Zasocitinib Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

In a study of 622 patients with rheumatoid arthritis, the efficacy and safety of four JAK inhibitors (tofacitinib, baricitinib, peficitinib, and upadacitinib) were found to be similar, with no significant differences in disease activity or remission rates after 6 months of treatment.

Predictive factors for achieving low disease activity included higher baseline disease activity and C-reactive protein levels, as well as previous treatment history, indicating that patient characteristics can influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. Hayashi, S., Tachibana, S., Maeda, T., et al.[2023]

In a real-world study of 260 ulcerative colitis patients treated with tofacitinib, adverse events (AEs) occurred in 15.7% of patients, with infections being the most common type.

Serious AEs, including herpes zoster (HZ) and venous thromboembolism (VTE), were reported, particularly in patients receiving a higher dose of 10 mg twice daily, suggesting that dose de-escalation may be beneficial to minimize risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis. Deepak, P., Alayo, QA., Khatiwada, A., et al.[2022]

Tofacitinib significantly improved symptoms in adults with active ankylosing spondylitis (AS), with 56.4% of patients showing at least a 20% improvement (ASAS20) compared to 29.4% in the placebo group after 16 weeks.

The safety profile of tofacitinib was acceptable, with no new safety risks identified; serious adverse events were low, and there were no deaths or major complications reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Deodhar, A., Sliwinska-Stanczyk, P., Xu, H., et al.[2022]

Upadacitinib has been evaluated for long-term safety in 6991 patients across various conditions, showing that it is generally well tolerated with similar rates of treatment-emergent adverse events (TEAEs) across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis.

While the overall safety profile is favorable, certain risks such as herpes zoster and non-melanoma skin cancer were higher in patients with rheumatoid arthritis and psoriatic arthritis compared to active comparators, indicating the need for careful monitoring in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. Burmester, GR., Cohen, SB., Winthrop, KL., et al.[2023]

In a study of 363 patients using Janus kinase inhibitors (JAKi) for rheumatoid arthritis, the average time from starting other treatments to beginning JAKi was 7.2 years, indicating a long treatment history before this therapy was introduced.

The introduction of JAKi was associated with increased healthcare costs, averaging 4819 € per patient, primarily due to hospitalizations and the costs of the JAKi themselves, suggesting a potential selective prescription pattern in line with treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Utilization, Healthcare Facilities Accesses and Costs of the First Generation of JAK Inhibitors in Rheumatoid Arthritis. Convertino, I., Lorenzoni, V., Gini, R., et al.[2023]

Tofacitinib has been evaluated for safety and efficacy in Crohn's disease through two phase II trials, showing no new safety concerns but also no significant improvement over placebo in the primary clinical response measure.

Despite the lack of significant results in larger trials, smaller studies and post hoc analyses suggest that tofacitinib may still provide clinical and biological benefits for some patients with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Tofacitinib in Crohn's Disease and IBD-U: A Multicenter Study From the TROPIC Consortium. Fenster, M., Alayo, QA., Khatiwada, A., et al.[2022]

A comprehensive analysis of 23,720 adverse event reports revealed that Janus kinase (JAK) inhibitors, particularly tofacitinib, are frequently associated with serious adverse events, including infections and thromboembolism.

Other reported adverse events include malignancies, interstitial lung diseases, and gastrointestinal disorders, indicating significant safety concerns that warrant further research and routine clinical monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews. Song, YK., Song, J., Kim, K., et al.[2022]

Tofacitinib has a consistent safety profile in psoriatic arthritis (PsA) similar to that observed in rheumatoid arthritis (RA), based on a review of 73,525 adverse event reports, with 5,394 cases related to PsA.

The analysis showed that the reporting rates for adverse events were higher for the modified release formulation compared to the immediate release, indicating potential differences in safety profiles based on the formulation used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis. Burmester, GR., Coates, LC., Cohen, SB., et al.[2023]

Tofacitinib is effective for treating rheumatoid arthritis across various patient demographics and treatment stages, supported by extensive clinical trial and real-world data.

Safety data from the ORAL Surveillance study indicates that tofacitinib can be used cautiously in older patients with cardiovascular risk factors, allowing for informed discussions between clinicians and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical scenarios-based guide for tofacitinib in rheumatoid arthritis. Mortezavi, M., Mysler, EF.[2023]

Tofacitinib, a selective Janus kinase inhibitor, successfully induced and maintained remission in a 9-year-old boy with moderately active ulcerative colitis (UC) after other biologic treatments failed.

This case suggests that tofacitinib is a safe and effective treatment option for pediatric patients with UC, even those who are steroid-dependent and refractory to other biologics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Japanese pediatric patient with refractory steroid-resistant ulcerative colitis successfully treated with Tofacitinib: A case report. Kakiuchi, T., Yoshiura, M.[2023]

Tofacitinib, an oral Janus kinase inhibitor, was found to be safe and well-tolerated in a study involving 95 healthy participants, with only mild adverse events like nausea and headache reported.

The pharmacokinetics of tofacitinib showed rapid absorption and elimination, indicating that it reaches peak serum concentration quickly and is eliminated from the body efficiently, which is important for its potential therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers. Krishnaswami, S., Boy, M., Chow, V., et al.[2022]

Tofacitinib is effective in treating rheumatoid arthritis in real-world settings, with 82% of the 50 patients achieving the treatment target after an average of 18 months of therapy.

The safety profile of tofacitinib aligns with previous studies, with the most common adverse event being herpes zoster, affecting 4% of patients, and some laboratory abnormalities noted in cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis (RA): A Retrospective Study From Two Centers in Jeddah, Saudi Arabia. Alzahrani, Z., Alhazmi, A., Almalki, H., et al.[2023]

In a study of 38 patients with moderate-to-severe ulcerative colitis treated with tofacitinib, 28.9% achieved steroid-free clinical remission by week 8, indicating some efficacy in real-world settings.

However, 53% of patients were primary non-responders at week 8, and there were significant safety concerns, including severe adverse events like pneumonia and emergency colectomy due to colon perforation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study. Hoffmann, P., Globig, AM., Thomann, AK., et al.[2020]

References

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

Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. [2023]

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

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis. [2022]

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

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Drug-Utilization, Healthcare Facilities Accesses and Costs of the First Generation of JAK Inhibitors in Rheumatoid Arthritis. [2023]

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

Real-World Effectiveness and Safety of Tofacitinib in Crohn's Disease and IBD-U: A Multicenter Study From the TROPIC Consortium. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews. [2022]

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

Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis. [2023]

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

Clinical scenarios-based guide for tofacitinib in rheumatoid arthritis. [2023]

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

Japanese pediatric patient with refractory steroid-resistant ulcerative colitis successfully treated with Tofacitinib: A case report. [2023]

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

Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers. [2022]

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

Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis (RA): A Retrospective Study From Two Centers in Jeddah, Saudi Arabia. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Tofacitinib in Treatment-Refractory Moderate to Severe Ulcerative Colitis: Real-World Experience from a Retrospective Multicenter Observational Study. [2020]