KT-621 for Healthy Participants

Overseen By Kymera Medical Director

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Kymera Therapeutics, Inc.

Disqualifiers: Respiratory, Gastrointestinal, Renal, others

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days for SAD, 38 days for MAD

120 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. However, since the study is for healthy participants, it is likely that you should not be on any regular medications. Please consult with the study team for specific guidance.

How is the drug KT-621 different from other treatments?

KT-621, which is related to ketamine, may have unique effects on the NMDA receptor, a part of the brain involved in pain and mood regulation. Unlike other treatments, it might also interact with specific transporters in the body, affecting how it is absorbed and distributed. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a first-in-human study to evaluate safety, pharmacokinetics, and pharmacodynamics of single and multiple dose levels of KT-621 in healthy male and female adult participants.

Eligibility Criteria

This trial is for healthy adults aged 19 to 55 who can follow study procedures and agree to use contraception. Participants must have a normal weight and BMI, no recent substance abuse, no significant health issues or abnormal lab results that could affect the study.

Inclusion Criteria

Evidence of a personally signed and dated informed consent document

Willingness and ability to comply with study procedures

Agreement to contraception requirements

Exclusion Criteria

Factors, conditions, or diseases that might interfere with treatment compliance or study conduct

Positive alcohol and drug tests at Screening and on admission to the CRU

Abnormal clinical laboratory safety test results at Screening and on admission to the CRU

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a single oral dose (SAD) or multiple oral doses (MAD) of KT-621 or placebo

14 days for SAD, 38 days for MAD

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 days for SAD, 38 days for MAD

Treatment Details

Interventions

• KT-621

Trial Overview The trial tests KT-621, a new drug taken by mouth, against a placebo in healthy people. It aims to understand how safe it is and how the body processes it when given once or multiple times at different doses.

Participant Groups

Group I: KT-621 Active Control 1 Intervention

Each participant receives either a single oral dose (SAD) or multiple oral doses (MAD) of KT-621.

Group II: Placebo Placebo Group 1 Intervention

Each participant receives either a single oral dose (SAD) or multiple oral doses (MAD) of matched placebo.

Who Is Running the Clinical Trial?

Kymera Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

850+

Findings from Research

Ketamine causes cytotoxic effects on human bladder cells in a dose- and time-dependent manner, leading to increased cell permeability and changes in cell cycle progression, which may contribute to bladder interstitial cystitis.

In a mouse model, ketamine treatment resulted in significant downregulation of keratin genes, particularly keratin 14, suggesting that these changes in gene expression play a critical role in the development of ketamine-induced cystitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice. Shen, CH., Wang, ST., Lee, YR., et al.[2018]

In a study involving 10 healthy volunteers, ketamine significantly reduced the binding of the [(123)I]CNS-1261 ligand to NMDA receptors, indicating its effectiveness as a competitor at the intra-channel PCP/ketamine/MK-801 site.

The results suggest that [(123)I]CNS-1261 is a specific ligand for the NMDA receptor's intra-channel site, which could be useful for studying NMDA receptor dynamics in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine displaces the novel NMDA receptor SPET probe [(123)I]CNS-1261 in humans in vivo. Stone, JM., Erlandsson, K., Arstad, E., et al.[2016]

K-601, an herbal formulation for influenza, contains 50 identified components, with 15 major compounds and 17 metabolites found in human plasma, indicating its complex chemical profile.

Pharmacokinetic studies revealed significant differences in how K-601 is absorbed between Chinese and African volunteers, with African subjects showing 4-10 times higher absorption of certain alkaloids, which could influence its efficacy and safety in different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers. Alolga, RN., Fan, Y., Zhang, G., et al.[2022]

Ketamine is taken up by specific transporter proteins (OCT1-3) in a way that depends on the concentration and pH, which could influence how it is absorbed in the intestines when taken orally.

The study found that while ketamine interacts with OCT transporters and P-glycoprotein (P-gp), it does not interact with MATE1/2K, suggesting that its absorption and distribution in the body may be primarily affected by these transporters rather than by renal excretion mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Affinity of Ketamine to Clinically Relevant Transporters. Keiser, M., Hasan, M., Oswald, S.[2019]

In a study of 36 patients with ketamine-induced cystitis (KC) and 9 control subjects, KC patients exhibited significantly higher symptom scores and reduced bladder capacity, indicating severe bladder dysfunction related to ketamine use.

The research identified microvascular injury and changes in endothelial cell characteristics as potential mechanisms contributing to bladder dysfunction in KC, highlighting the role of NMDAR1 expression and basement membrane thickening in the affected bladder tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microvascular Injury in Ketamine-Induced Bladder Dysfunction. Lin, CC., Lin, AT., Yang, AH., et al.[2018]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Biological effect of ketamine in urothelial cell lines and global gene expression analysis in the bladders of ketamine‑injected mice. [2018]

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

Ketamine displaces the novel NMDA receptor SPET probe [(123)I]CNS-1261 in humans in vivo. [2016]

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

Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers. [2022]

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

Affinity of Ketamine to Clinically Relevant Transporters. [2019]

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

Microvascular Injury in Ketamine-Induced Bladder Dysfunction. [2018]