Ensitrelvir for Drug Interaction Study

Overseen By Shionogi Clinical Trials Administrator Clinical Support Help Line

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Shionogi

Must not be taking: Oral contraceptives

Disqualifiers: Cardiovascular, Respiratory, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug ensitrelvir interacts with other medications, specifically a common oral contraceptive. Researchers aim to determine if ensitrelvir affects the contraceptives' function in the body. The trial involves women who are not currently on birth control and meet specific health criteria, excluding those with certain medical histories such as cancer or unexplained bleeding. Participants will receive varying doses of both the contraceptive and ensitrelvir over a set period. The trial seeks women who are not pregnant, not breastfeeding, and have a BMI between 18.5 and 30. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new drug.

Do I need to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, since the study is about drug interactions, it's possible that some medications might need to be paused. Please consult with the study team for specific guidance.

Is there any evidence suggesting that Ensitrelvir is likely to be safe for humans?

Research has shown that ensitrelvir is generally well-tolerated. Studies found that the body handles it well, allowing for just one dose per day, which makes it easy and convenient for participants. Additionally, ensitrelvir remains active in the body for about 48 hours after administration.

No major safety concerns have emerged in the available research, suggesting that the treatment is safe for humans. However, this study remains in an early phase. Researchers are closely monitoring for any possible side effects or safety issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ensitrelvir is unique because it acts as an antiviral with a novel mechanism of action, specifically targeting a virus's replication process. Unlike traditional treatments that might focus on symptom relief or boosting the immune response, ensitrelvir directly inhibits the virus's ability to multiply, potentially stopping the infection from spreading at its source. Researchers are excited about ensitrelvir's potential to offer a more direct and effective approach to managing viral infections compared to existing options.

What evidence suggests that Ensitrelvir might be an effective treatment for drug interactions?

Research has shown that ensitrelvir works against the Omicron variant of the virus that causes COVID-19. In clinical trials, it reduced symptoms of the virus. On average, participants taking ensitrelvir experienced symptoms for about 5.4 days, similar to the duration for those taking ritonavir, another antiviral drug. These studies suggest that ensitrelvir can effectively combat COVID-19 symptoms, particularly in newer variants like Omicron. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for healthy adult women with a BMI of ≥18.5 to ≤30.0 kg/m^2 who are not pregnant or breastfeeding, have not used oral contraceptives for at least 28 days, and agree to use effective contraception during the study. Women with significant health issues or history of certain cancers cannot participate.

Inclusion Criteria

Body mass index (BMI) within the range of ≥18.5 to ≤30.0 kilograms (kg)/square meter (m^2) at the screening

I am not pregnant or breastfeeding and meet the fertility criteria.

A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention

Exclusion Criteria

I don't have major health issues that could affect drug processing or pose risks with the study treatment.

Participants who are otherwise considered ineligible for the study by the investigator for any other reason

I have or am suspected to have had breast, endometrial, or cervical cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combined oral contraceptive for 24 days, with ensitrelvir high dose on Day 20 and low dose on Days 21 to 24

24 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ensitrelvir

Trial Overview The study is testing how Ensitrelvir interacts with combined oral contraceptives in the body. It aims to understand if taking Ensitrelvir affects how well the contraceptive works or if it changes Ensitrelvir's effectiveness.

How Is the Trial Designed?

Group I: Ensitrelvir Experimental Treatment 1 Intervention

Participants will receive multiple oral doses of a combined oral contraceptive (COC) (EE and DRSP) once daily for 24 days (Days 1 to 24) (in the fasted state on Days 18 to 24) in the morning. Participants will also receive ensitrelvir high dose on Day 20 and multiple oral doses of ensitrelvir low dose once daily on Days 21 to 24 in the fasted state.

Who Is Running the Clinical Trial?

Shionogi

Lead Sponsor

Trials

122

Recruited

42,100+

Dr. Isao Teshirogi

Shionogi

Chief Executive Officer since 2008

PhD in Pharmaceutical Sciences from the University of Tokyo

Dr. Takuko Sawada

Shionogi

Chief Medical Officer since 2022

MD from a recognized institution (specific details not found)

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10177727/

Evaluation of the Drug–Drug Interaction Potential ... The objectives of this study were to investigate the effect of ensitrelvir on the pharmacokinetics of CYP3A substrates, dexamethasone, prednisolone and ...

2. academic.oup.com academic.oup.com/ofid/article/12/7/ofaf327/8160297

Implementation of an Online Drug–Drug Interaction Screener ... In phase 2/3 trials (SCORPIO-SR and -HR), ensitrelvir demonstrated antiviral activity against Omicron SARS-CoV-2 variants and significantly reduced symptom ...

3. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/jcph.2247

Evaluation of Drug‐Drug Interactions of Ensitrelvir, a SARS ... In the in vitro inhibition study for transporters, ensitrelvir showed inhibitory potential for P-gp, BCRP, OATP1B1, OATP1B3, OCT1, and OAT3.

4. jphcs.biomedcentral.com jphcs.biomedcentral.com/articles/10.1186/s40780-025-00411-y

Drug-drug interaction between ensitrelvir and tacrolimus in a ... We report a case in which TAC levels were successfully managed in a patient with rheumatoid arthritis (RA) who received ensitrelvir for persistent COVID-19.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1473309925004827

Antiviral efficacy of oral ensitrelvir versus oral ritonavir- ... The restricted mean duration of symptoms over 1 week was 5·4 days (95% CI 5·2–5·7) in the ensitrelvir group, 5·4 days (5·1–5·6) in the ritonavir ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37171749/

Evaluation of the Drug-Drug Interaction Potential ... In addition, ensitrelvir at 375/125 mg showed CYP3A inhibitory potential similar to that at 750/250 mg. These findings can be used as a clinical ...

7. journals.asm.org journals.asm.org/doi/10.1128/aac.00632-22

Safety, Tolerability, and Pharmacokinetics of the Novel ... Ensitrelvir was well-tolerated and demonstrated favorable pharmacokinetics, including a long half-life, supporting once-daily oral dosing.

8. covid19-druginteractions.org covid19-druginteractions.org/site_news/43

Interactions with Ensitrelvir Ensitrelvir is considered to be a strong inhibitor of CYP3A4 and its inhibitory effect is predicted to mostly disappear ~10 days after the last dose.