Suzetrigine for Oral Contraceptive Interaction

Overseen By Medical Information

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Vertex Pharmaceuticals Incorporated

Must be taking: Oral contraceptives

Disqualifiers: Hypertension, Cardiovascular disease, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the medication Suzetrigine affects the function of oral contraceptives (birth control pills) in the body. Participants will take Suzetrigine along with either Norgestimate/Ethinyl Estradiol or Drospirenone/Ethinyl Estradiol, both common birth control pills. The trial aims to determine if Suzetrigine alters the effectiveness of these contraceptives. This study suits non-smokers or those who quit smoking over a year ago, have a body mass index (BMI) between 18 and 30, and weigh more than 50 kilograms (about 110 pounds). 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 medication.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have conditions that affect how drugs are absorbed or processed in your body, you might not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that suzetrigine, when used with birth control pills, has generally been well-tolerated in past studies. Some evidence indicates that suzetrigine did not cause significant changes in the levels of hormones like ethinyl estradiol or levonorgestrel, which are found in these contraceptives. This suggests a lower risk of unexpected side effects from changes in hormone levels.

However, suzetrigine can interact with other drugs and may cause side effects if taken with strong inhibitors that affect its processing in the body. Participants should inform their doctor about all medications they are taking to avoid these interactions.

This trial is in an early phase, marking one of the first times suzetrigine is tested in humans for this specific use. This phase focuses on understanding the treatment's safety, so unknown effects might still occur. Participants in such trials receive close monitoring to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about suzetrigine because it potentially offers a novel way to interact with oral contraceptives like Norgestimate/Ethinyl Estradiol (NGM/EE) and Drospirenone/Ethinyl Estradiol (DRSP/EE). Unlike standard hormonal contraceptives, which primarily work by preventing ovulation, suzetrigine might be capable of influencing how these contraceptives are metabolized in the body. This could lead to more effective or consistent contraceptive performance. Additionally, the unique dosing schedule of suzetrigine, administered every 12 hours, may provide a more consistent therapeutic effect, addressing gaps that current options might leave open.

What evidence suggests that this trial's treatments could be effective for oral contraceptive interaction?

This trial will evaluate the interaction of Suzetrigine with different oral contraceptives. Studies have shown that Suzetrigine does not significantly affect the efficacy of birth control pills. Research indicates that Suzetrigine does not alter the levels of ethinyl estradiol, a key hormone in many birth control pills, ensuring they continue to work as expected. Additionally, no significant changes were observed in how the body processed other hormones like levonorgestrel. Overall, evidence suggests that taking Suzetrigine with birth control pills should not impact their ability to prevent pregnancy. Participants in this trial will receive Suzetrigine alongside either Norgestimate/Ethinyl Estradiol or Drospirenone/Ethinyl Estradiol to further assess these interactions. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy female participants who don't smoke or haven't smoked in the last year, have a body mass index (BMI) between 18.0 and 30.0, and weigh over 50 kilograms. It's designed to see how Suzetrigine affects the way their bodies process birth control pills.

Inclusion Criteria

My BMI is between 18.0 and 30.0.

I weigh more than 50 kg.

I have not smoked for at least a year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single dose of DRSP/EE on Days 1 and 20, and SUZ every 12 hours from Days 7 through 25

4 weeks

Treatment Part B

Participants receive a single dose of NGM/EE on Days 1 and 22, and SUZ every 12 hours from Days 9 through 29

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Suzetrigine

Trial Overview

The study is testing Suzetrigine (SUZ), a medication intended for pain management, to understand its impact on oral contraceptives specifically DRSP/EE and NGM/EE which are common forms of birth control pills.

How Is the Trial Designed?

Group I: Part B: SUZ with Norgestimate/Ethinyl Estradiol (NGM/EE) Experimental Treatment 2 Interventions

Participants will receive a single dose NGM/EE on Days 1 and 22. Participants will also receive SUZ every 12 hours (q12h) from Days 9 through 29.

Group II: Part A: SUZ with Drospirenone/Ethinyl Estradiol (DRSP/EE) Experimental Treatment 2 Interventions

Participants will receive a single dose of DRSP/EE on Days 1 and 20. Participants will also receive SUZ every 12 hours (q12h) from Days 7 through 25.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Published Research Related to This Trial

In a study involving 35 HIV-infected women, those taking protease inhibitors (PI) showed significantly higher serum concentrations of norethindrone (NET), indicating that PIs inhibit the metabolism of this progestin-only contraceptive.

The findings suggest that progestin-only pills like NET may be more effective in HIV-infected women on PI regimens, as evidenced by a 1.5 times higher area under the curve for NET in the PI group compared to controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of protease inhibitors on steady-state pharmacokinetics of oral norethindrone contraception in HIV-infected women. Atrio, J., Stanczyk, FZ., Neely, M., et al.[2021]

Oral contraceptive steroids can have significant drug interactions, where certain medications, especially enzyme-inducing anticonvulsants like phenobarbital and rifampicin, can reduce the effectiveness of contraceptives, potentially leading to breakthrough bleeding or unintended pregnancy.

Conversely, some substances like ascorbic acid and paracetamol can increase blood levels of ethinylestradiol, the active component in many oral contraceptives, which may affect contraceptive efficacy, particularly in women taking high doses of these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug interactions with oral contraceptives. Back, DJ., Orme, ML.[2018]

Co-administration of lamotrigine with a combined oral contraceptive significantly reduced the plasma levels of lamotrigine, indicating a clinically relevant pharmacokinetic interaction that may require dosage adjustments for lamotrigine.

While the combined oral contraceptive's effectiveness was not compromised (as indicated by unchanged ethinyloestradiol levels and maintained suppression of ovulation), a modest decrease in levonorgestrel levels was observed, along with reports of intermenstrual bleeding in some subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Sidhu, J., Job, S., Singh, S., et al.[2018]

In two studies involving 27 and 29 healthy women, oral tazarotene (up to 6 mg) did not significantly alter the pharmacokinetics of the oral contraceptive Ortho-Novum 1/35, indicating that tazarotene can be safely coadministered without affecting contraceptive efficacy.

The hormonal levels of norethindrone, ethinylestradiol, LH, and FSH remained within acceptable ranges, suggesting that tazarotene does not interfere with the hormonal balance maintained by the contraceptive, ensuring its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tazarotene does not affect the pharmacokinetics and efficacy of a norethindrone/ethinylestradiol oral contraceptive. Yu, Z., Yu, D., Walker, PS., et al.[2018]

Mothers taking combined oral contraceptives can safely breast-feed, as the concentrations of hormones like levonorgestrel and ethinylestradiol in breast milk are low.

Newer progestogens such as desogestrel, gestodene, and norgestimate show good bioavailability, but their effectiveness can be influenced by factors like sex hormone binding globulin (SHBG) levels and interactions with other medications, which may affect contraceptive efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of contraceptive steroids. An update. Shenfield, GM., Griffin, JM.[2018]

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Suzetrigine for Oral Contraceptive Interaction

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The present study was conducted to investigate the influence of the strong CYP3A4 inhibitor ketoconazole (KTZ) on the pharmacokinetics of drospirenone (DRSP)

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Drospirenone and ethinyl estradiol (oral route)

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur.

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Journavx (suzetrigine) dosing, indications, interactions, ...

suzetrigine decreases levels of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients ...

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Drospirenone: Uses, Interactions, Mechanism of Action

Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation.