Levonorgestrel + Meloxicam for Birth Control

Overseen By William McPheat, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: InnovaGyn, Inc.

Must not be taking: Hormonal contraceptives, Anticoagulants

Disqualifiers: Alcohol abuse, Hypertension, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new birth control method that combines levonorgestrel (a hormone used in emergency contraception) and meloxicam (a nonsteroidal anti-inflammatory drug) to determine its effectiveness in delaying ovulation in women. Researchers aim to see if this combination can delay ovulation by at least seven days without causing unexpected bleeding or other side effects. Women with regular menstrual cycles who are considered obese (BMI of 30 or higher) and have no rapid weight changes may be suitable candidates for this trial. Participants will compare the effects of the new combination to a placebo, aiding researchers in understanding its effectiveness and side effects. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in birth control methods.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are using hormonal contraception, certain medications that interfere with hormonal contraceptives or NSAIDs, or medications on the exclusionary list. It's best to discuss your current medications with the trial team.

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

Research has shown that levonorgestrel, a main ingredient in Plan B, is generally safe for emergency contraception. Most people tolerate it well. Common side effects include nausea, tiredness, and headaches, which are usually mild and temporary.

Meloxicam, often used to reduce inflammation and pain in conditions like arthritis, is also generally safe. However, it can cause side effects such as stomach pain or dizziness.

When used together, levonorgestrel and meloxicam aim to delay ovulation. Studies on this combination have not identified major safety issues, but side effects similar to those of each drug alone might occur. As this is a Phase 2 trial, researchers continue to study its safety closely, monitoring how well participants handle the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most birth control options involve hormones like estrogen and progestin, but Levonorgestrel plus Meloxicam offers a unique approach. Researchers are excited because this combination uses levonorgestrel, a well-known emergency contraceptive, paired with meloxicam, a non-steroidal anti-inflammatory drug (NSAID) that might enhance contraceptive effectiveness. This combination might work quickly and provide an alternative for those who cannot use traditional hormonal methods. By targeting different biological pathways, this treatment has the potential to be both effective and accessible to a broader range of individuals.

What evidence suggests that levonorgestrel plus meloxicam might be an effective treatment for delaying ovulation in obese women with normal menses?

Research has shown that levonorgestrel, a key ingredient in many emergency contraceptives, is highly effective. When used correctly, it can reduce the chance of pregnancy by about 89%. Some participants in this trial will receive a combination of levonorgestrel and meloxicam, which researchers are testing to determine if it can further delay ovulation. Early results suggest that this combination might delay ovulation by up to seven days, potentially enhancing birth control effectiveness. ^{2 4 6 7 8}

Who Is on the Research Team?

Andrea Lukes, MD

Principal Investigator

Carolina Woman's Research and Wellness Center

Are You a Good Fit for This Trial?

This trial is for obese women with regular menstrual cycles. Participants will undergo two treatment cycles, one with a placebo and the other with levonorgestrel plus meloxicam. They must keep daily logs, provide urine samples, have ultrasound scans, and allow blood draws.

Inclusion Criteria

Subject is willing to collect daily first morning urines and store them until brought to the study site

I have an intact uterus and both ovaries.

Regular menstrual cycles with an interval of 24 to 32 days. If postpartum or post-second trimester abortion, she must have 2 spontaneous menses prior to enrollment. If the subject has had a first trimester pregnancy loss or abortion, she must have one spontaneous menses prior to enrollment

Exclusion Criteria

I am not taking any medications listed as not allowed for the trial.

Women who plan a major surgical procedure during the study

My thyroid disorder is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Cycle 1

Participants receive placebo treatment and undergo monitoring for ovulation and adverse events

2 weeks

4 visits (in-person) for ultrasound and blood sampling

Treatment Cycle 2

Participants receive levonorgestrel plus meloxicam treatment and undergo monitoring for ovulation and adverse events

2 weeks

4 visits (in-person) for ultrasound and blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person) for final evaluation

What Are the Treatments Tested in This Trial?

Interventions

• Levonorgestrel
• Meloxicam

Trial Overview Researchers are testing if ovulation can be delayed by at least 7 days using levonorgestrel combined with meloxicam versus a placebo in obese women. The study also looks for differences in unscheduled bleeding or side effects between treatments.

How Is the Trial Designed?

Group I: Levonorgestrel plus meloxicam Active Control 2 Interventions

The active comparator is levonorgestrel 1.5 milligram (mg) and meloxicam 15 milligram (mg) taken together orally and repeated 48 hours later.

Group II: Placebo Placebo Group 1 Intervention

The placebo is calcium carbonate 750 milligram (mg) known as TUMS. Each participant will take one tablet orally and repeat 48 hours later.

Levonorgestrel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Plan B One-Step for:

• Emergency contraception

Approved in European Union as Levonelle for:

• Emergency contraception

Approved in Canada as Postinor for:

• Emergency contraception

Approved in Japan as Levonorgestrel for:

• Emergency contraception

Who Is Running the Clinical Trial?

InnovaGyn, Inc.

Lead Sponsor

Trials

2

Recruited

40+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

In a study involving 24 healthy HIV-negative women, the presence of efavirenz (EFV) significantly reduced the effectiveness of Plan B (levonorgestrel, LNG), with a 56% decrease in the area under the concentration-time curve (AUC(12)).

Despite the reduced levels of LNG when taken with EFV, the drug was well tolerated with no severe side effects, highlighting the need for women on EFV to consider higher doses of LNG for effective contraception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and Efavirenz. Carten, ML., Kiser, JJ., Kwara, A., et al.[2021]

A study involving 24 healthy male volunteers found that a single 15 mg dose of meloxicam in tablet form is bioequivalent to the same dose in suspension form, meaning they have similar absorption and effectiveness.

Both formulations of meloxicam were well tolerated with no reported adverse events, indicating their safety for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the formulation on the bioequivalence of meloxicam: tablet and suspension. Helmy, SA., El Bedaiwy, HM.[2019]

In a study of 42 adolescent girls using Postinor (0.75 mg Levonorgestrel) for emergency contraception, no pregnancies occurred, demonstrating its effectiveness as a contraceptive method.

The most common mild side effects included nausea (12.4%) and intermenstrual bleeding (30.9%), which resolved within three days, indicating that while there are some adverse reactions, they are generally manageable and do not require treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Emergency contraception with levonorgestrel in adolescents]. Tanchev, S., Shentov, B.[2013]

Aomei meloxicam and Mobic meloxicam were found to be bioequivalent in a study involving 24 healthy volunteers, meaning they have similar pharmacokinetic profiles in both fasting and fed conditions.

The study showed that both medications were well tolerated, with all reported adverse events being mild, indicating a good safety profile for Aomei meloxicam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single-Site, Single-Dose, Randomized, Open, 2-Period, 2-Sequence, Crossover Bioequivalence Study. Yu, J., Wang, Y., Wu, Y., et al.[2022]

Meloxicam is a selective COX-2 inhibitor that provides strong anti-inflammatory and pain relief effects while exhibiting low gastrointestinal toxicity, making it safer than many traditional NSAIDs.

In clinical studies, meloxicam has proven effective for various conditions such as rheumatoid arthritis and osteoarthritis, without affecting bleeding time or platelet aggregation, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Meloxicam (Mobic): a review of its pharmacological and clinical profile]. Ogino, K., Saito, K., Osugi, T., et al.[2019]

In a phase 3 study involving patients aged 40 and older with osteoarthritis, low-dose SoluMatrix meloxicam (5 mg and 10 mg) significantly reduced pain levels after 12 weeks compared to placebo, indicating its efficacy in managing OA-related pain.

The treatment was associated with common adverse events such as headache and diarrhea, but overall, it suggests that low-dose SoluMatrix meloxicam could be a safer alternative for patients needing NSAID therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose SoluMatrix meloxicam in the treatment of osteoarthritis pain: a 12-week, phase 3 study. Altman, R., Hochberg, M., Gibofsky, A., et al.[2018]

A randomized double-blind placebo-controlled trial tested the efficacy of oral emergency contraception combining levonorgestrel and piroxicam, involving a significant number of participants to ensure robust results.

The study found that this combination may enhance the effectiveness of emergency contraception compared to standard methods, suggesting a potential new option for preventing unintended pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding piroxicam to levonorgestrel increased emergency contraception effectiveness. Batur, P.[2023]

Meloxicam, a new NSAID, was found to be well tolerated in healthy male volunteers, showing high anti-inflammatory potency with low risk of causing ulcers.

The study indicated that coadministration of aspirin slightly increased meloxicam levels in the blood, but these changes were not clinically significant, meaning no dosage adjustments are necessary when taking meloxicam with aspirin, Maalox, or cimetidine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction of meloxicam with cimetidine, Maalox, or aspirin. Busch, U., Heinzel, G., Narjes, H., et al.[2019]

Meloxicam is a highly effective COX-2 inhibitor for treating osteoarthritis and rheumatoid arthritis, with a long elimination half-life of approximately 20 hours, allowing for steady-state plasma concentrations to be reached within 3-5 days.

The drug shows a favorable safety profile, as it does not require dosage adjustments for elderly patients or those with hepatic insufficiency or moderate renal dysfunction, and it has no significant interactions with common medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the clinical pharmacokinetics of meloxicam. Türck, D., Roth, W., Busch, U.[2019]

In a study analyzing adverse reactions from three nonsteroidal anti-inflammatory drugs (NSAIDs) during their first year on the market, aceclofenac showed a significantly lower incidence of total adverse reactions compared to meloxicam and rofecoxib, with rates of 8.7, 24.8, and 52.6 per million defined daily doses, respectively.

Aceclofenac was associated with fewer gastrointestinal and cardiovascular adverse effects than both meloxicam and rofecoxib, suggesting it may be a safer option among these NSAIDs, challenging the presumed benefits of COX-2 selective inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of spontaneous notifications of adverse reactions with aceclofenac, meloxicam, and rofecoxib during the first year after marketing in the United Kingdom. Raber, A., Heras, J., Costa, J., et al.[2021]

In a pilot study involving 14 women (9 with normal BMI and 5 obese), a new long-acting injectable contraceptive formulation of levonorgestrel butanoate (LB) showed that most participants returned to ovulation before the expected 6-month period, indicating its potential efficacy as a contraceptive.

Interestingly, the obese group returned to ovulation earlier than the normal BMI group, with 60% of obese participants ovulating within 90 days compared to none in the normal BMI group, suggesting that the formulation may have different effects based on body mass index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levonorgestrel butanoate intramuscular injection does not reliably suppress ovulation for 90 days in obese and normal-BMI women: a pilot study. Edelman, AB., Cherala, G., Li, H., et al.[2018]

In a study of 84 women using the etonogestrel implant, those treated with combined oral contraceptive pills (COCP) experienced a significantly higher rate of stopping bleeding within 7 days (76.2%) compared to those treated with NSAIDs (35.7%).

The mean duration of bleeding was also significantly shorter in the COCP group (7.29 days) compared to the NSAID group (10.57 days), indicating that COCP is more effective for managing bleeding irregularities in etonogestrel implant users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of bleeding irregularities among etonogestrel implant users: Is combined oral contraceptives pills or nonsteroidal anti-inflammatory drugs the better option? Upawi, SN., Ahmad, MF., Abu, MA., et al.[2020]

Intravenous (IV) meloxicam, a COX-2 inhibitor, has been shown to significantly reduce post-operative pain and decrease the need for opioids, based on recent clinical trials.

The review indicates that meloxicam IV is an effective and well-tolerated option for managing moderate to severe pain during the perioperative period, addressing limitations of oral formulations that have a slow onset of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meloxicam in the management of post-operative pain: Narrative review. Bekker, A., Kloepping, C., Collingwood, S.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5102175/

Appreciation for analysis of how levonorgestrel works and ... The FDA has stated that Plan B is 89 percent effective in the prevention of expected clinical pregnancies (PDR 2005, s.v. “Plan B, Barr Laboratories, Inc.,” 779 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4216625/

Emergency contraception review: evidence-based ... Although the package insert indicates use for only 72 hours after unprotected sex, some research has shown levonorgestrel ECPs to be effective up to 4 days ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05695352

Oral Levonorgestrel Plus Meloxicam, IG-002 Delays ... Secondary outcomes are menstrual cramps, vaginal bleeding, nausea, and headache, and changes in blood pressure, pulse, and interval between menstrual periods in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2590151624000042

Maximizing the effectiveness of 1.5 mg levonorgestrel for ... Results. Taking LNG-EC immediately after sex could potentially reduce the risk of unintended pregnancy by 91%. However, population-average maximum attainable ...

5. withpower.com withpower.com/trial/phase-2-pregnancy-prevention-5-2022-d1eb5

Levonorgestrel + Meloxicam for Birth Control This clinical trial determines if an oral medication taken within 2 days of anticipated ovulation will delay ovulation by 7 days.

6. fda.gov fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/plan-b-one-step-15-mg-levonorgestrel-information

Plan B One-Step (1.5 mg levonorgestrel) Information Plan B One-Step is an emergency contraceptive, a backup method of birth control. Emergency contraception is used to reduce the chance of pregnancy after ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/021998lbl.pdf

Plan B One-Step (levonorgestrel) Tablet - accessdata.fda.gov Plan B One-Step is a progestin-only emergency contraceptive indicated for prevention of pregnancy following unprotected intercourse or a known or.

8. mayoclinic.org mayoclinic.org/drugs-supplements/levonorgestrel-oral-route/description/drg-20074413

Levonorgestrel (oral route) - Side effects & dosage Levonorgestrel is an emergency contraceptive that is used to prevent pregnancy after unprotected sex or after failure of another birth control method.