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

Trial Summary

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.

What data supports the idea that Levonorgestrel + Meloxicam for Birth Control is an effective drug?

The available research shows that adding piroxicam, which is similar to meloxicam, to levonorgestrel increased the effectiveness of emergency contraception. This suggests that combining meloxicam with levonorgestrel could also improve its effectiveness as a birth control method. ^{1 2 3 4 5}

What safety data is available for Levonorgestrel and Meloxicam as birth control?

The provided research primarily focuses on the safety and pharmacokinetics of Meloxicam, a non-steroidal anti-inflammatory drug, in various formulations and conditions. Meloxicam has been shown to be well-tolerated in healthy volunteers, with mild adverse events reported. However, the studies do not specifically address the combination of Levonorgestrel and Meloxicam for birth control, nor do they provide safety data for this specific use. Further research would be needed to evaluate the safety of this combination for birth control purposes. ^{6 7 8 9 10}

Is the drug Levonorgestrel + Meloxicam a promising option for birth control?

Yes, the drug Levonorgestrel + Meloxicam is promising for birth control because Meloxicam is well-tolerated, has a reliable effect, and is bioequivalent in different forms, meaning it works the same way in the body regardless of how it's taken. ^{6 7 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to compare the delay in ovulation between placebo to levonorgestrel plus meloxicam in obese women with normal menses. The main questions it aims to answer are: 1. Ovulation will be delayed by ≥7 days following the first dose of levonorgestrel plus meloxicam compared to ovulation within 3 days following the first dose of placebo. 2. There will be no difference in unscheduled vaginal bleeding or adverse events between the two treatments \[placebo versus levonorgestrel plus meloxicam\]. Participants will: * undergo two treatment cycles the 1st uses placebo and the 2nd is levonorgestrel plus meloxicam, * maintain daily diary logs for adverse events, unscheduled bleeding, and onset, cessation, and amount of menstrual bleeding, * collect daily first morning voided urine from menstrual day 9 to 24, * undergo transvaginal ultrasound for ovarian follicle development on menstrual days 9, 11,13 and 14. * allow a blood sample to be drawn on days with ultrasound scans. * Take 1st placebo and levonorgestrel plus meloxicam under observation when dominant ovarian follicle is 17 ±1.0 millimeters (mm) in diameter and 2nd dose 48 hours later. Researchers will compare the placebo cycle to levonorgestrel plus meloxicam to see if ovulation is delayed, there is unscheduled vaginal bleeding, menstrual onset is delayed or there is an abnormal amount or duration of menses, there is any difference in treatment emergent side effects and any change in vital signs

Research Team

Andrea Lukes, MD

Principal Investigator

Carolina Woman's Research and Wellness Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. Bulgaria pubmed.ncbi.nlm.nih.gov

[Emergency contraception with levonorgestrel in adolescents]. [2013]

3. Egypt pubmed.ncbi.nlm.nih.gov

Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and Efavirenz. [2021]

4. Australia 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? [2020]

5. United States 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. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Effect of the formulation on the bioequivalence of meloxicam: tablet and suspension. [2019]

7. United States 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. [2022]

8. England 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. [2018]

9. India pubmed.ncbi.nlm.nih.gov

Meloxicam in the management of post-operative pain: Narrative review. [2020]

10. New Zealand 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. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Interaction of meloxicam with cimetidine, Maalox, or aspirin. [2019]

12. England pubmed.ncbi.nlm.nih.gov

A review of the clinical pharmacokinetics of meloxicam. [2019]

13. Japan pubmed.ncbi.nlm.nih.gov

[Meloxicam (Mobic): a review of its pharmacological and clinical profile]. [2019]