SUVN-I6107 Safety Study

Overseen By Ramakrishna Nirogi

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Suven Life Sciences Limited

Disqualifiers: Pregnancy, Lactation, Recent illness, others

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

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

Trial Summary

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 study team or your doctor.

What makes the drug SUVN-I6107 unique compared to other treatments?

SUVN-I6107 is unique because it is being studied for its safety and effectiveness in a clinical trial setting, and it is compared to a placebo (a dummy treatment with no active ingredients) to evaluate its true effects. This approach helps determine if SUVN-I6107 offers any benefits over existing treatments or if it is safe for use. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is 1) to investigate how safe and tolerable SUVN-I6107 is after a single oral dose at increasing dose levels and multiple oral doses at increasing dose levels, 2) to determine the pharmacokinetic (PK) profile after single and multiple ascending oral doses, 3) to investigate the effects of food on SUVN-I6107 pharmacokinetics and 4) to evaluate the pharmacodynamic (PD) effects of single and multiple ascending oral doses of SUVN-I6107 on quantitative electroencephalogram (qEEG) and event-related potential (ERP) assessments.

Eligibility Criteria

This trial is for healthy adults with normal blood and urine tests, a BMI of 18.0-30.0 kg/m2 (or up to 32.0 for part of the study), weighing between 50-100 kg, who can avoid alcohol, caffeine, and certain foods before each study visit. Pregnant or breastfeeding individuals or those planning pregnancy are excluded.

Inclusion Criteria

Ability and willingness to abstain from alcohol-, caffeine-, and methylxanthine-containing beverages or food from 48 hours prior to each admission to the clinical facility until study discharge

All values for hematology and clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations at screening and at admission

My BMI is between 18.0-30.0 for Segment 1 or 18.0-32.0 for Segment 2, and my weight is between 50-100 kg.

Exclusion Criteria

I am not pregnant, breastfeeding, planning to become pregnant, or donate eggs during or within 30 days after the study.

My partner is pregnant, breastfeeding, or might become pregnant during the study or within 3 months after.

I haven't had any major illnesses or surgeries in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive single ascending doses of SUVN-I6107 to assess safety, tolerability, and pharmacokinetics

11 days

Multiple visits for dosing and assessments

Multiple Ascending Dose (MAD)

Participants receive multiple ascending doses of SUVN-I6107 for 14 consecutive days to assess safety, tolerability, and pharmacokinetics

14 days

Daily visits for dosing and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 days

Treatment Details

Interventions

• Placebo
• SUVN-I6107

Trial Overview The trial is testing SUVN-I6107's safety after one dose and over multiple doses in different amounts. It also looks at how the body processes it with and without food and its effects on brain activity measured by qEEG and ERP assessments.

Participant Groups

Group I: Single Ascending Dose Experimental Treatment 2 Interventions

single ascending doses administered orally

Group II: Multiple Ascending Dose Experimental Treatment 2 Interventions

multiple ascending doses administered orally for 14 days.

Who Is Running the Clinical Trial?

Suven Life Sciences Limited

Lead Sponsor

Trials

14

Recruited

1,700+

Findings from Research

SPH3127 demonstrated a dose-dependent increase in exposure and effectively suppressed plasma renin activity by up to 90% for 24 hours, indicating its potential efficacy in managing conditions related to renin activity.

The drug was well tolerated among healthy individuals, with only mild adverse events reported in 29.2% of single-dose and 33.3% of multiple-dose participants, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Jing, S., Xu, R., Yang, K., et al.[2021]

The maximum tolerated dose (MTD) of E7107 was determined to be 4.0 mg/m², with dose-limiting toxicities primarily involving gastrointestinal issues such as grade 3 diarrhea and nausea in some patients.

Pharmacodynamic analysis showed that E7107 effectively inhibited pre-mRNA processing of target genes in a dose-dependent manner, indicating its potential clinical activity despite no complete or partial responses observed during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors. Eskens, FA., Ramos, FJ., Burger, H., et al.[2022]

AMG 181 demonstrated favorable pharmacokinetics with a long half-life of approximately 31 days and high bioavailability (82%-99%) after subcutaneous administration, indicating it is well-absorbed and maintained in the body for an extended period.

In ulcerative colitis patients, AMG 181 led to remission and mucosal healing without serious adverse events, suggesting it is a safe and effective treatment option for inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases. Pan, WJ., Köck, K., Rees, WA., et al.[2021]

The study found that auto-injector systems (A-INJ) effectively delivered both placebo and active injectates while maintaining blinding in randomized controlled trials, with no significant difference in delivery rates compared to conventional syringes.

Investigators reported no concerns about becoming unblinded when using the A-INJ, highlighting its potential to improve the integrity of clinical trials without the need for additional modifications to the placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinding Is Seeing: A Single-Centre Study Into the Viability of Auto-Injectors for Blinded-Drug Administration in Randomised Controlled Trials. Aggarwal, V., Taubel, J., Lorch, U., et al.[2023]

Intravenous (IV) siponimod was found to be well tolerated in healthy subjects, with no significant effects on heart rate and similar safety profiles to oral siponimod, indicating its potential for safe use in clinical settings.

The pharmacokinetics showed that IV siponimod resulted in higher peak exposure compared to oral dosing, supporting the development of a rapid IV titration regimen for patients, particularly those with conditions like intracerebral hemorrhage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Intravenous Siponimod: A Randomized, Open-label Study in Healthy Subjects. Shakeri-Nejad, K., Gardin, A., Gray, C., et al.[2020]

References

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

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. [2021]

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

Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors. [2022]

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

Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases. [2021]

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

Blinding Is Seeing: A Single-Centre Study Into the Viability of Auto-Injectors for Blinded-Drug Administration in Randomised Controlled Trials. [2023]

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

Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Intravenous Siponimod: A Randomized, Open-label Study in Healthy Subjects. [2020]